12275 results for ""statistically+reactive"+taxa+in+microbial+community"

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• McGill EMC Community projects Release 7 for cell line "hTERT RPE1"

  Complete reference epigenome (as defined by IHEC) of normal hTERT RPE1 cell line as well as hTERT RPE1 cell lines engineered to express EPC1-PHF1 and JAZF1-SUZ12 fusion proteins, found in Endometrial Stromal Sarcoma.

  Dataset EGAD00001007680

• HipSci - Human Induced Pluripotent Stem Cells Initiative

  Human induced pluripotent stem (iPS) cells can be generated from adult tissues and differentiated into a range of specific cell types (Yamanaka and Blau, 2010). They therefore provide unprecedented opportunities for investigating disease mechanisms and understanding the phenotypic consequences of genetic variation within the normal population. HipSci brings together diverse constitutents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. Between 2013 and 2016 we aim to generate iPS cells from over 500 healthy individuals and 500 individuals with genetic disease. We will then use these cells to discover how genomic variation impacts on cellular phenotype and identify new disease mechanisms. Strong links with NHS investigators will ensure that studies on the disease-associated cell lines will be linked to extensive clinical information. Further key features of the project are an open access model of data sharing; engagement of the wider clinical genetics community in selecting patient samples; and provision of dedicated laboratory space for collaborative cell phenotyping and differentiation.

  Study EGAS00001001465

• A Genome-Wide Association Study on Cataract and HDL in the Personalized Medicine Research Project Cohort

  The primary goals of this project are to develop and validate electronic phenotyping algorithms, to accurately identify cases and controls while maintaining a positive predictive value (PPV) of >95%, and to conduct a genome wide association study that advances understanding of two specific yet interrelated disease states, while simultaneously engaging the community in these research efforts. Lipid abnormalities and cataracts are both diseases of public health significance, they share common risk factors, and they are both complex diseases which likely have many genes contributing to disease development. Whole genome association studies with these two outcomes and environmental risk factors could yield novel data about the etiology of the two separate outcomes as well as their interaction. PhenX is a project designed to prioritize Phenotypes and eXposure measures for Genome-wide Association Studies (GWAS). The PhenX Toolkit is a valuable resource for researchers who are planning or expanding a study and would like to incorporate well established measures that have been recommended by experts in the field. We are currently interested in gene-environment interactions for "age related cataract".

  Study phs000170

• Autozygosity pilot - British-Pakistani from Birmingham 2

  The offspring of first cousin marriages have ~6% of their genome autozygous, i.e. homozygous identical by descent, or even more if there was further consanguinity in their ancestry. In the UK there are large populations with very high first cousin marriage rates of 20-50%. Sequencing the exomes of a sample of these individuals has the potential both to support genetic health programmes in these populations, and to provide genetic research information about rare loss of function mutations. This pilot study based on existing British-Pakistani cohort samples from Birmingham will identify homozygous individuals for almost all variants down to an allele frequency around 1%, plus individuals carrying hundreds of new homozygous rare loss-of-function variants, and will support development of community relations and ethics for a wider study currently being designed. The data deposited in the EGA consists of low coverage whole exome sequencing on these samples.

  Dataset EGAD00001001026

• Autozygosity pilot - British-Pakistani from Birmingham

  The offspring of first cousin marriages have ~6% of their genome autozygous, i.e. homozygous identical by descent, or even more if there was further consanguinity in their ancestry. In the UK there are large populations with very high first cousin marriage rates of 50-80%. Sequencing the exomes of a sample of these individuals has the potential both to support genetic health programmes in these populations, and to provide genetic research information about rare loss of function mutations. This pilot study based on existing British-Pakistani cohort samples from Birmingham will identify homozygous individuals for almost all variants down to an allele frequency around 1%, plus individuals carrying hundreds of new homozygous rare loss-of-function variants, and will support development of community relations and ethics for a wider study currently being designed. The data deposited in the EGA consist of low coverage whole exome sequencing on these samples.

  Dataset EGAD00001001025

• NextGen Consortium: GENESiPS Study: Identifying the Gene Networks of Insulin Resistance

  Variability in induced pluripotent stem cell (iPSC) lines remains a roadblock for disease modeling and regenerative medicine. Through linear mixed models we have described different sources of gene expression variability from RNA sequencing data in 317 human iPSC lines from 101 individuals. We found that ~50% of genome-wide expression variability is explained by variation across individuals and identified a set of expression quantitative trait loci that contribute to this variation. These analyses coupled with allele specific expression show that iPSCs retain a subject-specific gene expression pattern. Pathway enrichment and key driver analyses, based on predictive causal gene networks, found that Polycomb targets explain a significant part of the non-genetic variability present in iPSCs within and across individuals. These publically available iPSC lines and genetic datasets will be a resource to the scientific community and will open new avenues to reduce variability in iPSCs and improve their utility in disease modeling. SNP array data from individuals included in RNA-seq transcriptome profiling study of human induced pluripotent stem cells to characterize gene expression variation across individuals and within multiple iPSC lines from the same individual. Genotyping was performed on patient blood. Data availability: SNP-genotyping: dbGaP - current study RNA-seq counts: GEO - GSE79636 FASTQ files: SRA - SRP072417

  Study phs001139

• Whole-Genome sequencing of hepatocellular carcinomas

  The French ICGC project on liver tumors is coordinated by Pr Jessica Zucman-Rossi and funded by Inca (French Institute for Cancer). The aim of the present project is to identify the catalog of somatic and germline mutations in liver tumors using whole genome and whole exome sequencing together with CGH-SNP, methylome and transcriptomic profiling. For this purpose, a series of 500 liver tumors are collected through the French National Liver Collection and these samples will be analyzed using the different omics technologies. The data will be deposited in the ICGC and EGA database to be publically available for the scientific community. Hepatocellular carcinoma (HCC) accounts for more than 90% of liver cancers, and is a major health problem. It is the 3rd cause of cancer-related mortality. Advances in genomic analyses have formed a comprehensive understanding of different underlying pathobiological layers resulting in hepatocarcinogenesis. Thus, the development of next-generation sequencing technologies has made it possible to generate more comprehensive catalogues of somatic alteration events (single nucleotide substitutions, structural variations, and epigenetic changes) in liver cancer genome than ever before. The dataset will include 50 whole genome sequencing tumor/germline pairs, of which 6 are deposited in February 2014.

  Study EGAS00001000706

• COVID19 Host Genetic Initiative

  The COVID-19 host genetics initiative is a bottom-up collaborative effort that has three main goals: 1. Provide an environment to foster the sharing of resources to facilitate COVID-19 host genetics research (e.g. protocols, questionnaires). 2. Organize analytical activities across studies to identify genetic determinants of COVID-19 susceptibility and severity. 3. Provide a platform to share the results from such activities, as well as the individual-level data where possible, to benefit the broader scientific community. Here, we release the harmonized individual-level data for the subset of individuals who participated in COVID-19 HGI. Please refer to this data dictionary: https://docs.google.com/spreadsheets/d/1whu_MjShXxbdoAJMCYxZ5C-vWOcRivwfWglTcBRNZgQ/edit#gid=470747846 Please cite both Nakanishi, T el al. J Clin Invest 2021 (PMID: 34597274) and COVID-19 Host Genetics Initiative, Nature 2021 (PMID: 34237774) when you use these data for your publications.

  Study EGAS00001005304

• Jackson Heart Study - Images

  The Jackson Heart Study (JHS) is a large, community-based, observational study that recruited 5,306 African American adults from three counties (Hinds, Madison and Rankin) in the Jackson, MS area. Participants age 35-84 years at baseline were enrolled from each of 4 recruitment pools: (1) random, 17%, (2) volunteer, 30%, (3) currently enrolled in the Atherosclerosis Risk in Communities (ARIC) Study, 31%, and (4) secondary family members, 22% (family study participants were age≥21 years). Data available include medical history, physical examination, blood/urine analytes, and interview questions on areas such as physical activity, stress, coping and spirituality, racism and discrimination, socioeconomic position, and access to health care. Extensive clinical phenotyping includes anthropometrics, electrocardiography, carotid ultrasound, ankle-brachial blood pressure index, echocardiography, CT chest and abdomen for coronary and aortic calcification, liver fat, subcutaneous and visceral fat measurements, and cardiac MRI. Participants have been contacted annually by telephone to update information, confirm vital status, document interim medical events, hospitalizations and functional status, and obtain sociocultural information. Ongoing cohort surveillance includes abstraction of medical records and death certificates for relevant International Classification of Diseases (ICD) codes and adjudication of nonfatal events and deaths.

  Study phs003747

• Organ maturation in preparation for birth (Peds RFA) to develop a tissue resource and a single-cell atlas of organ development and maturation for dissemination among the scientific and clinical community: RNA (2025-10-14)

  Knowledge about abnormal organ development is important to understand pathology and to develop novel treatment approaches for individuals with congenital and acquired disease. Most of our current understanding is based on examination of tissues from the embryo and early foetus, collected from women undergoing termination of pregnancy in the first trimester (third) of pregnancy. There is very little known about normal and abnormal organ development from a developmental perspective during the crucial last two-thirds of pregnancy when much remodelling of foetal tissues occurs. This study will generate a single-cell atlas of late-foetal lungs, blood, heart, bone and immune organs. . This dataset contains all the data available for this study on 2025-10-14.

  Dataset EGAD00001015737

• The National Heart, Lung, and Blood Institute (NHLBI)-funded Next Generation Genetic Association Studies (NextGen) Consortium: Phenotyping Lipid traits in iPS derived hepatocytes Study (PhLiPS Study)

  The goal of the PhLiPS study is to create a library of induced pluripotent stem cell (iPSC) lines and iPSC-derived hepatocytes of diverse genotypes for use in metabolic profiling and interrogating lipid phenotypes. These cell lines were created as a part of the Next Generation Genetic Association Studies (Next Gen) Program, which was a five-year, $80 million program to investigate functional genetic variation in humans by assessing cellular profiles that are surrogates for disease phenotypes. To achieve this, researchers from multiple institutions across the U.S. were awarded grants to derive iPSC lines from more than 1,500 individuals representing various conditions as well as healthy controls for use in functional genomic ("disease in a dish") research. This extensive panel includes a diverse set of age, gender, and ethnic backgrounds, and therefore will be an invaluable tool for evaluations across demographics. Further enhancing the utility of these cell lines are data sets such as phenotyping, GWAS, genome sequencing, gene expression and -omics analyses (e.g., lipidomic, proteomic, methylomic) that can be matched to the cell lines. The PhLiPS Study focuses on individuals free of cardiovascular disease or with lipoprotein metabolism disorders in the community served by the Hospital of the University of Pennsylvania.

  Study phs001341

• National Institute of General Medical Sciences (NIGMS) Human Genetic Cell Repository Human Variation Panels including 100 African-Americans (HD100AA), 100 Caucasians (HD100CAU), 100 Han People of Los Angeles (HD100CHI) and 100 Mexican American Community of Los Angeles (HD100MEX)

  The Human Genetic Cell Repository is sponsored by the National Institute of General Medical Sciences (NIGMS) with the mission of supplying scientists with the materials for accelerating disease gene discovery and functional studies. The resources available include highly-characterized, contaminant-free cell cultures and high quality, well-characterized DNA samples derived from these cultures, both subjected to rigorous quality control. The Repository was established in 1972 at Coriell and contains more than 9,500 cell lines, primarily fibroblasts and transformed lymphoblasts. The Repository has a major emphasis on inherited diseases and chromosomally aberrant cell lines. In addition, it contains a large collection dedicated to understanding human variation that includes samples from populations around the world, the CEPH collection, the Polymorphism Discovery Resource, Human Variation and many apparently healthy controls. The Human Variation collection provides cell lines and DNA samples from a variety of populations. The panels of African-Americans (HD100AA) and Caucasians (100CAU) used for this study are comprised of samples present in the Repository that were originally collected over the years from apparently healthy people to be used as "controls", for example, unaffected family members of persons with identified mono-genetic diseases. The samples for the Han people of Los Angeles (HD100CHI) and the Mexican American Community of Los Angeles (HD100MEX), however, were collected relatively recently from volunteers, identified as member of these communities, specifically for use in these panels. The Coriell Genotyping and Microarray Center in conjunction with the NIGMS repository used the Affymetrix Genome-Wide Human SNP 6.0 platform to genotype 400 samples from the NIGMS human variation panels. The populations genotyped included Americans of African, Caucasian, Mexican, and Han Chinese ancestry. The Affymetrix SNP 6.0 array detects approximately 940,000 SNPs and provides copy number information for more than 900,000 additional locations across the genome.

  Study phs000211

• A somatic reference standard for cancer genome sequencing with COLO829

  Identification of somatic alterations in cancer has become feasible with the massive adoption of next generation sequencing. However, due to variability in sequencing and informatics pipelines, a common somatic reference is needed. We thus performed paired whole genome sequencing of a metastatic melanoma cell line (COLO829) and a matched lymphoblastoid line (COLO829BL) across three institutions (TGen, Illumina, Genome Sciences Centre at the British Columbia Cancer Agency). We performed a meta-analysis of all data, in combination with the originally reported analysis of these cell lines by Pleasance et al (PMID: 20016485), and report a somatic reference standard based on consensus events. DNA extractions, library preparation, sequencing, and analysis were separately performed at each site. Results were compiled with sequence data previously generated for the cell lines to identify true positive variants, collectively representing a somatic reference standard. Overall, common somatic events include point mutations, small insertion/deletions, and genes affected by concurrent copy number changes. We additionally show divergence of somatic mutations in COLO829 associated with differences in cell line lineage. We present this reference to the community as a standard for enabling interpretation and identification of somatic mutations across institutions and analytical pipelines.

  Study EGAS00001001385

• Pancreatic, Small-intestinal and Pulmonary Neuroendocrine Tumors

  Purpose: The primary origin of neuroendocrine tumor metastases can be difficult to determine by histopathology alone, but is critical for therapeutic decision making. DNA methylation-based profiling is now routinely used in the diagnostic workup of brain tumors. This has been enabled by the availability of cost-efficient array-based platforms. We have extended these efforts to augment histopathological diagnosis in neuroendocrine tumors. Experimental Design and Results: We compiled data of 69 small-intestinal, pulmonary, and pancreatic neuroendocrine tumors. These data were used to build a ridge regression calibrated random forest classification algorithm (NEN-ID) that predicts the origin of tumor samples with high accuracy (> 95%). The model was validated during 3x3 nested cross validation and tested in a local (n=26) and external (n=172) cohort. In addition, we show that our diagnostic approach is robust across a range of possible confounding experimental parameters such as tumor purity and array quality. A software infrastructure and online user interface was built to make the model available to the scientific community. Conclusions: This DNA methylation-based prediction model can be used in the workup for patients with neuroendocrine tumors of unknown primary. To facilitate validation and clinical implementation, we provide a user-friendly, publicly available web-based version of NEN-ID.

  Study EGAS00001004878

• Autozygosity pilot - Born in Bradford (2017-05-11)

  The offspring of first cousin marriages have ~6% of their genome autozygous, i.e. homozygous identical by descent, or even more if there was further consanguinity in their ancestry. In the UK there are large populations with very high first cousin marriage rates of 20-50%. Sequencing the exomes of a sample of these individuals has the potential both to support genetic health programmes in these populations, and to provide genetic research information about rare loss of function mutations. This pilot study based on existing cohort samples from the Born In Bradford study will identify homozygous individuals for almost all variants down to an allele frequency around 1%, plus individuals carrying hundreds of new homozygous rare loss-of-function variants, and will support development of community relations and ethics for a wider study currently being designed. The data deposited in the EGA consist of low coverage whole exome sequencing on these samples. This dataset contains all the data available for this study on 2017-05-11.

  Dataset EGAD00001003329

• Massachusetts General Hospital/Eisai National Institute of Mental Health (NIMH) Genetics Initiative Alzheimer's Disease GWAS - Affymetrix GeneChip Human Mapping 500K Array Set

  This study cohort was collected as part of the National Institute of Mental Health (NIMH) Alzheimer's disease Genetics Initiative Study. Recruitment of families, predominantly sibling, for the cohort was focused on local memory disorder clinics, nursing homes, and the surrounding community. Clinical evaluation was performed at the University of Alabama at Birmingham, Johns Hopkins University, and Massachusetts General Hospital/Harvard Medical School. Informed consent was obtained from all study participants, for participants with extensive cognitive impairment, a legal guardian or caregiver with power of attorney provided consent. To determine age of onset, a creditable informer was interviewed and medical records were evaluated.

  Study phs000483

• Mid-pass Whole-genome Sequencing in a Malagasy Cohort Uncovers Body Composition Associations

  The majority of human genomic research studies have been conducted in European-ancestry cohorts, reducing the likelihood of detecting potentially novel and globally impactful findings. Here, we present mid-pass whole-genome sequencing data and a genome-wide association study in a cohort of 264 self-reported Malagasy individuals from three locations on the island of Madagascar. We describe genetic variation in this Malagasy cohort, providing insight into the shared and unique patterns of genetic variation across the island. We observe phenotypic variation by location, and find high rates of hypertension particularly in the Southern Highlands sampling site as well as elevated self-reported malaria prevalence in the West Coast site relative to other sites. After filtering to a subset of 214 minimally-related individuals, we find a number of genetic associations with body composition traits, including many variants that are only observed in African populations or populations with admixed African ancestry from the 1000 Genomes Project. This study highlights the importance of including diverse populations in genomic research for the potential to gain novel insights, even with small cohort sizes. This project was conducted in partnership and consultation with local stakeholders in Madagascar and serves as an example of genomic research that prioritizes community engagement and that has potential impacts on our understanding of human health and disease.

  Study EGAS50000000496

• Contextual and Health Behavior Effects on Epigenetic Aging Among Africans in the Family and Community Health Studies

  The Family and Community Health Studies (FACHS) is a longitudinal examination of health and health related behaviors in African American families. The original study cohort consisted of 867 African American parent-child dyads from Georgia and Iowa who were ascertained in cooperation with local school districts. The key inclusion criteria for participating in the study were the presence of an adolescent in the 5th grade (approximately 10-11 years old) who self-identified as African American (i.e., the Target) and the participation of a primary caretaker (PC) for the Target. The clinical and biological data included in this collection are from the Target (i.e., FACHS-T) portion of these studies of these African American parent-child dyads. The initial wave of behavioral assessments of the FACHS-T subjects was conducted in 1997-98 (Wave 1), with seven subsequent ascertainments, Wave 2 (1999–2000), Wave 3 (2002–2003), Wave 4 (2005–2006), Wave 5 (2007–2009), Wave 6 (2010–2011), Wave 7 (2014–2016) and Wave 8 (2019-2021). Full interviews were obtained at each wave of the study with the exact content of the wave varying as a function of developmental age. These interviews of the FACHS-T subjects collected a wide variety of data including the following: perceived discrimination; socioeconomic status; substance use exposure; common internalizing and externalizing disorders such as depression, substance use, and conduct disorder; school efficacy; peer support and perceived parenting practices. Biological sampling of the FACHS-T subjects was conducted at three time points. Saliva DNA was collected at Wave 5 while full phlebotomy was conducted at Waves 7 and 8. The genome wide methylation data listed below is derived from the whole blood DNA samples collected at Wave 8 and Wave 9. The genome wide genotyping data was determined using DNA from the Wave 7 samples. The clinical and biological data available herein are those from 309 FACHS-T subjects who participated in both Wave 7 and Wave 8, and who consented for deposition of their data in dbGAP.

  Study phs003723

• Whole Genome Association Study of Visceral Adiposity in the Health Aging and Body Composition (Health ABC) Study

  The Health Aging and Body Composition (Health ABC) Study is a NIA-sponsored cohort study of the factors that contribute to incident disability and the decline in function of healthier older persons, with a particular emphasis on changes in body composition in old age. Between 4/15/97 and 6/5/98 the Health ABC study has recruited 3,075 70-79 year old community-dwelling adults (41% African-American), who were initially free of mobility and activities of daily living disability. The key components of Health ABC include a baseline exam, annual follow-up clinical exams, and phone contacts every 6 months to identify major health events and document functional status between clinic visits. The core yearly examination for HEALTH ABC includes measurement of body composition by dual energy x-ray absorptio-metry (DXA), walking ability, strength, an interview that includes self-report of limitations, and a medication survey, weight. At baseline, visceral adiposity was measured by computerized tomography (CT). Provision has been made for banking of blood specimens and extracted DNA (HealthABC repository). The overall goal of this project is to identify genetic determinants of visceral adiposity. Genetic samples from 2932 unrelated participants were evaluated with a genome-wide scan.

  Study phs000169

• Genomic_Advances_in_Sepsis__GAinS__genotyping

  This cohort comprises a subset of pateints enrolled in the Genomic Advances in Sepsis (GAinS) study, an established biobank of adult sepsis patients. Patients with sepsis due to community acquired pneumonia or faecal peritonitis were recruited from 35 hospitals across the UK from 2005-2018, with samples for functional genomics and detailed clinical information collected over the first five days of ICU admission. DNA was extracted from buffy coat or whole blood samples using the Qiagen DNA extraction protocol, the automated Maxwell Blood purification kit (Promega), or the QIAamp Blood Midi kit protocol (Qiagen). Genotyping data were generated using the Illumina HumanOmniExpress BeadChip (295 patients), the Infinium CoreExome BeadChip (655 patients), and the Infinium Global Screening Array BeadChip (307 patients). Genotyping QC and imputation into the Haplotype Reference Consortium was perfomed within each batch. The datasets were combined and following post-imputation filtering data were available on 1168 samples. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/

  Study EGAS00001007786

• Autozygosity pilot - Born in Bradford (2014-11-20)

  The offspring of first cousin marriages have ~6% of their genome autozygous, i.e. homozygous identical by descent, or even more if there was further consanguinity in their ancestry. In the UK there are large populations with very high first cousin marriage rates of 20-50%. Sequencing the exomes of a sample of these individuals has the potential both to support genetic health programmes in these populations, and to provide genetic research information about rare loss of function mutations. This pilot study based on existing cohort samples from the Born In Bradford study will identify homozygous individuals for almost all variants down to an allele frequency around 1%, plus individuals carrying hundreds of new homozygous rare loss-of-function variants, and will support development of community relations and ethics for a wider study currently being designed. The data deposited in the EGA consist of low coverage whole exome sequencing on these samples.Data Access is controlled by the Wellcome Trust Sanger Institute DAC and the Born In Bradford Executive Group. This dataset contains all the data available for this study on 2014-11-20.

  Dataset EGAD00001001079

• PREDICT-HD Huntington Disease Study

  The purpose of this project is to make clinical measurements from the PREDICT-HD consortium available through the dbGaP mechanism. The phenotype data will first be converted into a community open standard and subsequently exported to dbGaP for archival and open access distribution of the results of the studies. This will permit members of the scientific community to utilize a permanent resource for investigating the interactions of phenotypes upon an international cohort of early Huntington Disease. In version 2 cut of the data we provided HD CAG repeat lengths for both alleles as well as enrollment age of all participants. We have also generated unique identifiers prospectively compatible with the larger initiative GWAS in Huntington's Disease project (also on DbGaP). As such, the version 1 cut of the data was mainly proof of concept and should be deprecated. Going forward, all updates will add-on to version 2 cut of the data. In version 3 cut of the data, we provided baseline or the first usable MRI T1-weighted imaging analysis subcortical and cortical segmentations and cortical parcellations based on a customized Freesurfer 5.2 pipeline developed at The University of Iowa. The customizations to the standard pipeline were mainly to improve bias field correction and image normalization such that segmentation of gray, white, internal csf, dura and surface CSF are optimized for the Freesurfer pipeline. There are 1111 subjects with results in this data release. In version 4 cut of the data, we provided all longitudinal clinical measurements for all subjects (total of 1476) assessmented or enrolled through the end of 2013. Additionally, we are providing measurements on 39 baseline FDG PET images spatially normalized by SPM5 into MNI space, relative regional metabolic values computed in 120 volumes of interest (VOI) defined in the Automated Anatomical Labeling (AAL) Atlas (Tzourio-Mazoyer et al. 2002), and global metabolic values calculated by SPM standard mean voxel value (within per image fullmean/8 mask). This project is a funded ancillary study of PREDICT-HD. In version 5 cut of the data, we provided the first of many forthcoming results from ancilliary studies of PREDICT-HD. In this data cut, we provide individual subject results derived from structural MRI data. The earliest MRI session for each subject was used. The results summarized represent source based morphometry loading coefficients for 23 components (see: "Patterns of Co-Occurring Gray Matter Concentration Loss across the Huntington Disease Prodrome", Ciarochi et al., 2016, Front Neurol. 2016; 7: 147, Published online 2016 Sep 21. doi: 10.3389/fneur.2016.00147]. In this version 6 cut of the data, we provide a full set of derived data, more than 10,000 raw MRI images, and ancillary study data sets. For sample information please link to: PREDICT-HD Biospecimen Resources

  Study phs000222

• CPTAC: Proteogenomic Studies of Ovarian Tumor Responses to Agents Targeting the DNA Damage Response

  There is a critical unmet need for predictors of chemo-refractory High-grade serous ovarian cancer (HGSOC). Despite over 3 decades of research on platinum responses in cancer, no predictive biomarker has been translated into clinical use. Predictors of refractory disease could spare these patients the unnecessary toxicity of a platinum-based regimen and provide a means to triage these patients to clinical trials to identify effective therapies for refractory disease. This study has approached the development of a predictor in a novel way enabling detection of a multi-analyte panel biomarker capable of detecting a subset of refractory HGSOCs with high specificity and implicating potential treatment vulnerabilities for refractory disease. We reported the first proteogenomic analysis of platinum refractoriness in HGSOC and made the novel dataset available as a resource to the community, including a ProTrack portal: http://ptrc.cptac-data-view.org/. Detailed proteogenomic profiles were generated for this study from a retrospective cohort of 242 treatment-naive HGSOCs with enriched representation of "exceptional non-responders" (i.e., patients with chemo-refractory disease). Whole genome sequence (WGS) and RNA seq FASTQ files are available through dbGaP. Proteomic data are available through the NCI Proteomic Data Commons (PDC): https://pdc.cancer.gov/pdc/.

  Study phs003152

• The_Genomic_Advances_in_Sepsis__GAinS__RNA_seq

  Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. This cohort comprises a subset of patients enrolled in the Genomic Advances in Sepsis (GAinS) study, an established biobank of adult sepsis patients. Patients with sepsis due to community acquired pneumonia or faecal peritonitis were recruited from 34 hospitals across the UK from 2005-2018, with samples for functional genomics and detailed clinical information collected on the first, third and/or fifth day following ICU admission. RNA was extracted from leukocytes isolated at the bedside using LeukoLOCK kits. We have previously identified sepsis response signatures (SRSs), transcriptomic endotypes that are associated with differential early mortality (Davenport et al, Lancet Respir Med, 2016; Burnham et al, AJRCCM, 2017) and response to treatment in a clinical trial (Antcliffe et al, AJRCCM, 2018). We generated RNA sequencing data on 903 samples, including 134 samples repeated from our previously released microarray data. Libraries were prepared using NEB Ultra II Library Prep kits (Illumina) and sequenced on a NovaSeq 6000. Reads were aligned to the reference genome (GRCh38) using STAR and gene counts quantified using featureCounts (annotation Ensembl v99). Counts were TMM-normalised and log-transformed. Following QC, processed data were available on 864 samples from 667 unique patients.

  Study EGAS00001003772

• RNA-seq profiling of NKX6.1 reporter iPSC lines for isolation and analysis of functionally relevant neuronal and pancreas populations

  We generated human induced pluripotent stem cell (iPSC) lines with a GFP reporter inserted in the endogenous NKX6.1 locus. Characterisation of the reporter lines demonstrated faithful GFP labelling of NKX6.1 expression during pancreas and motor neuron differentiation. We performed three independent in vitro differentiations towards the pancreatic endocrine lineage. We FACS-purified GFP positive and negative cells from stage 7 cultures, and generated Smart-Seq2 RNA-sequencing libraries for the pre-sorted cells, as well as the two GFP-sorted cell populations. Gene expression profiling by RNA-sequencing reveals that the NKX6.1-positive population closely resembles mature human beta cells and the functional evaluation of purified populations shows that the glucose-responsive beta-like cells are enriched within the NKX6.1-positive population. These reporter lines provide a valuable resource to the scientific community for the derivation of functional relevant pancreas and neuronal cell subtypes.

  Dataset EGAD00001003911

• Genomic Advances in Sepsis (GAinS) genotyping

  This cohort comprises a subset of patients enrolled in the Genomic Advances in Sepsis (GAinS) study, an established biobank of adult sepsis patients. Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Patients with sepsis due to community acquired pneumonia or faecal peritonitis were recruited from 35 hospitals across the UK from 2005-2018, with samples for functional genomics and detailed clinical information collected over the first five days of ICU admission to investigate how host genetics affects the individual repsonse to sepsis. DNA was extracted from buffy coat or whole blood samples using the Qiagen DNA extraction protocol, the automated Maxwell Blood purification kit (Promega), or the QIAamp Blood Midi kit protocol (Qiagen). Genotyping data were generated using the Illumina HumanOmniExpress BeadChip (295 patients), the Infinium CoreExome BeadChip (655 patients), and the Infinium Global Screening Array BeadChip (307 patients). Genotyping QC and imputation into the Haplotype Reference Consortium was perfomed within each batch. The datasets were combined and following post-imputation filtering data were available on 1168 samples.

  Dataset EGAD00001015369

• NIDCD Otitis Media Genetic Susceptibility and Middle Ear Microbial Shifts

  The study funded by R01 DC015004 aims to: (1) Identify rare OM susceptibility variants within families and in probands; and (2) Identify differences in the middle ear microbiome due to OM susceptibility variants. This study will also elucidate mechanisms responsible for the formation and growth of cholesteatoma, and bony erosion and complications due to cholesteatoma e.g. intracranial, hearing/vestibular loss, facial nerve palsy. A better understanding of cholesteatoma pathogenesis will potentially reveal novel drug targets, which can lead to new non-surgical therapies for cholesteatomatous OM. Our specific aims for this administrative supplement are: Aim 1 -- Perform RNA-sequencing using cholesteatoma samples collected from Filipino and Colorado patients who will be screened for FUT2, SPINK5 and A2ML1 variants; and Aim 2 -- Using network analysis, identify bone-expressed proteins potentially interacting with FUT2, SPINK5 or A2ML1, then test protein expression in archival human temporal bone in direct contact with cholesteatoma.

  Study phs001941

• Chromatin accessibility maps of chronic lymphocytic leukemia identify subtype-specific epigenome signatures and transcription regulatory networks

  Chronic lymphocytic leukemia (CLL) is characterized by substantial clinical heterogeneity, despite relatively few genetic alterations. To provide a basis for studying epigenome deregulation in CLL, we established genome-wide chromatin accessibility maps for 88 CLL samples from 55 patients using the ATAC-seq assay, and we also performed ChIPmentation and RNA-seq profiling for ten representative samples. Based on the resulting dataset, we devised and applied a bioinformatic method that links chromatin profiles to clinical annotations. Our analysis identified sample-specific variation on top of a shared core of CLL regulatory regions. IGHV mutation status – which distinguishes the two major subtypes of CLL – was accurately predicted by the chromatin profiles, and gene regulatory networks inferred for IGHV-mutated vs. IGHV-unmutated samples identified characteristic differences between these two disease subtypes. In summary, we discovered widespread heterogeneity in the chromatin landscape of CLL, established a community resource for studying epigenome deregulation in leukemia, and demonstrated the feasibility of chromatin accessibility mapping in cancer cohorts and clinical research.

  Dataset EGAD00001002110

• McGill EMC Community projects Release 7 for cell line "lung epithelial"

  Complete reference epigenome (as defined by IHEC) of a lung epithelial cell line with non-small Cell Lung Adenocarcinoma

  Dataset EGAD00001007679

• Submitters and requesters Statistics

  EGA Statistics Bibliography Growth Community Archive Distribution Catalogue Here, we show the amount and global distribution of submitters and requesters Requester accounts created by country The below figure represents the number of requester accounts by country. In most of the cases cases, country was inferred from the requester email domain. Those requesters whose email domain could not be assigned to a country such as @gmail.com, are not included. Note that a requester is a user that has had a granted permission at some point in time. Requester Accounts Created by Country Download as PNG Download as JPG Download as WEBP Download as CSV map pie mapChart('requester-country', 'https://stats.ega-archive.org/requester/country') pieChart('requester-country-pie-chart', 'https://stats.ega-archive.org/requester/country','Requester accounts created by country') Requester accounts created by year The below figure represents the number of requester accounts by year. Note that a requester is a user that has had a granted permission at some point in time. Requester Accounts Created by Year Download as PNG Download as JPG Download as WEBP Download as CSV barChart('requester-year', 'https://stats.ega-archive.org/requester/year', ['Requester Accounts', 'Years'], true) Industry requester accounts The below figure represents the top 15 industry requesting companies. Industry Requester Accounts Download as PNG Download as JPG Download as WEBP Download as CSV pieChart('industry-requester-accounts', 'https://stats.ega-archive.org/industry/requester/accounts', 'Industry Requester Accounts') Submitter accounts created by country The below figure represents the number of submitter accounts by country. Location was infered from the requester email domain. Submitter Accounts Created by Country Download as PNG Download as JPG Download as WEBP Download as CSV map pie mapChart('submitter-accounts', 'https://stats.ega-archive.org/submitter/accounts/country') pieChart('submitter-accounts-pie-chart', 'https://stats.ega-archive.org/submitter/accounts/country','Submitter accounts created by country') Submitter accounts created by year The below figure represents the number of submitter accounts by year. Submitter Accounts Created by Year Download as PNG Download as JPG Download as WEBP Download as CSV barChart('submitter-users-year', 'https://stats.ega-archive.org/submitter/users/year', ['Submitter Accounts', 'Years'], true) DAC Members by Country The below figure represents the number of DAC members by country. DAC Members by Country Download as PNG Download as JPG Download as WEBP Download as CSV map pie mapChart('dac-members-by-country', 'https://stats.ega-archive.org/dac_member/country') pieChart('dac-members-by-country-pie-chart', 'https://stats.ega-archive.org/dac_member/country','DAC members by country')

  Documentation about/statistics/community

• Stressors and Health Study

  ObjectivesThe objectives of the Stressors and Health Study were to: (1) examine the prevalence of stressors and health outcomes and (2) assess differences in the associations between multi-level stressors and health outcomes, and (3) explore the protective and adaptive factors in the associations between multi-level stressors and health outcomes. Background Stressors have been posited to explain disparities in health. However, no surveys to our knowledge have simultaneously collected multiple stressors at various levels and the coping strategies used to deal with these stressors. Measuring these factors can provide a better understanding of the stressors experienced by specific groups and the impact that these experiences have on their health and health practices. In addition, exploring the various resilience and coping strategies employed to deal with stressors can help design appropriate interventions to reduce health disparities. Participants Participants included 1000 White, 1000 Black or African American, 1000 Latino or Hispanic, 1000 Asian, 500 American Indian or Alaska Native, 500 Native Hawaiian or Pacific Islander, and 500 mixed or multi-race adults (≥18 years) across the United States. Design The Stressors and Health Study is a cross-sectional online survey of adults across the US. A sampling frame (target population) of US residents based on the American Community Survey (ACS) was constructed using a rigorous two-step sampling matching approach to establish national representation.

  Study phs004019

• Center for Sub-Cellular Genomics

  A cell is a highly complex system with distributed molecular physiologies in structured sub-cellular compartments whose interplay with the nuclear genome determine the functional characteristics of the cell. A classic example of distributed genomic processes is found in neurons. Learning and memory require modulation of individual synapses through RNA localization, localized translation, and localized metabolites, such as those from dendritic mitochondria. Dendrites of neurons integrate distributed synaptic signals into both electrical and nuclear transcriptional response. Dysfunction of these distributed genomic functions in neurons can result in a broad spectrum of neuropsychiatric diseases such as bipolar and depressive disorders, autism, among others. The Center for Sub-Cellular Genomics' (CSG) mission is to develop new technologies to enable the dissection of complex genomic interactions within a single cell. New technologies include methods to target DNA and RNA sampling at sub-cellular resolution in live cells; high-throughput isolation and microfluidics chemistry for sub-cellular fractions; sub-cellular resolution mass-spectrometry; and computational tools for analysis of sub-cellular genomics data. The new technologies developed by CSG will enable the broader genomics community to associate sub-cellular processes to cell function and dysfunction. These technologies will be utilized in the center to generate a comprehensive atlas of genomic signatures of sub-cellular compartments in the mammalian neuron system. The technologies and neuron-focused data obtained here will be relevant to neurodegenerative and neuropsychiatric diseases including schizophrenia, depression, autism spectrum disorder, traumatic brain injury, and Alzheimer's.

  Study phs002120

• NHLBI TOPMed: The Jackson Heart Study (JHS)

  Since there is a greater prevalence of cardiovascular disease among African Americans, the purpose of the Jackson Heart Study (JHS) is to explore the reasons for this disparity and to uncover new approaches to reduce it. The JHS is a large, community-based, observational study whose 5306 participants were recruited from among the non-institutionalized African-American adults from urban and rural areas of the three counties (Hinds, Madison, and Rankin) that make up the Jackson, MS, metropolitan statistical area (MSA). Jackson is the capital of Mississippi, the state with the largest percentage (36.3%) of African Americans in the United States. The JHS design included participants from the Jackson ARIC study who had originally been recruited through random selection from a drivers' license registry. Approximately six months before the JHS was to begin, an amendment to the federal Driver's Privacy Protection Act was passed that changed the level of consent for public release of personal information from driver's license lists from an "opt out" to an "opt in" basis. The Mississippi Highway Patrol was no longer able to release a complete listing of all persons with driver's licenses or state identification cards, which prevented its use in the JHS. New JHS participants were chosen randomly from the Accudata America commercial listing, which provides householder name, address, zip code, phone number (if available), age group in decades, and family components. The Accudata list was deemed to provide the most complete count of households for individuals aged 55 years and older in the Jackson MSA. A structured volunteer sample was also included in which demographic cells for recruitment were designed to mirror the eligible population. Enrollment was opened to volunteers who met census-derived age, sex, and socioeconomic status (SES) eligibility criteria for the Jackson MSA. In addition, a family component was included in the JHS. The sampling frame for the family study was a participant in any one of the ARlC, random, or volunteer samples whose family size met eligibility requirements. Eligibility included having at least two full siblings and four first degree relatives (parents, siblings, children over the age of 21) who lived in the Jackson MSA and who were willing to participate in the study. No upper age limit was placed on the family sample. Known contact information was obtained during the baseline clinic examination from the index family member with a verbal pedigree format to identify name(s), age(s), address (es), and telephone number(s). Recruitment was limited to persons 35-84 years old except in the family cohort, where those 21 years old and above were eligible. Only persons who otherwise met study criteria but were deemed to be physically or mentally incompetent by trained recruiters were excluded from study eligibility.1 1 Wyatt SB, Diekelmann N, Henderson F, Andrew ME, Billingsley G, Felder SH et al. A community-driven model of research participation: the Jackson Heart Study Participant Recruitment and Retention Study. Ethn Dis 2003; 13(4):438-455 (PMID: 14632263).

  Study phs000964

• Transcriptomic Profile of Whole Blood Cells from Elderly Subjects fed Probiotic Bacteria Lactobacillus rhamnosus GG ATCC 53103 (LGG) in a Phase I Open Label Study

  Open label study to evaluate the safety of Lactobacillus rhamnosus GG ATCC 53103 (LGG) in elderly subjects. Fifteen healthy elderly volunteers, ages 65-80 were enrolled in a study in which they received LGG capsules containing 1 x 1010 CFU, twice daily for 28 days and were followed through day 56. The study subjects completed a daily diary, a telephone call on study days 3, 7 and 14 and study visits at the Massachusetts General Hospital Clinical Research Center at baseline, day 28 and day 56. During each visit, the subject diary, interim history, potential adverse effects and concomitant medications were reviewed and vital signs and a physical examination were performed. Routine blood tests were obtained to monitor for safety during visits and nasopharyngeal and stool samples were collected for microbiome analysis. Volunteers interested in participating in the effect of LGG probiotic on the Human whole Blood Transcriptome substudy also had blood drawn for DNA and RNA extraction, after signing the substudy consent form. The main objective of the study was to assess the safety and tolerability of 2 x 1010 CFU LGG administered orally to elderly subjects for 28 days. Secondary objectives were to evaluate the richness and microbial diversity in nasopharyngeal and stool specimens using pyrosequencing, and to compare cytokine production in response to bacterial stimulation by following the kinetics of mRNA expression of pro and anti-inflammatory genes and different signaling pathways, in relation to changes in stool Bifidobacterium and Lactobacillus spp. The study was reviewed and approved by the Partners Human Research Committee (IRB # 2010P001695) and was registered at ClinicalTrials.gov (NCT01274598). The main results regarding the clinical signs and safety of intervention is published in PLoS One. 2014 Dec 1;9(12):e113456. doi: 10.1371/journal.pone.0113456. eCollection 2014. PMID: 25438151. RNA sequencing for transcriptome analysis was only done in 11 of the 15 subjects as RNA integrity and quantity had to be optimal for the three times where blood was collected in order for a subject to be included in the study. The information regarding the microbiome data associated with this study is presented in a separate paper, which can be found at dbGaP study accession, phs000896, and PMID: 25873374.

  Study phs000928

• Lactobacillus rhamnosus GG ATCC (LGG) as an immune adjuvant for influenza vaccination in the elderly

  Double blind Randomized Controlled trial to evaluate the safety of Lactobacillus rhamnosus GG ATCC 53103 (LGG) vs placebo in elderly receiving Trivalent Inactivated Influenza Vaccine (TIV) (study 1) or Double blind Randomized Controlled trial to evaluate the safety of Lactobacillus rhamnosus GG ATCC 53103 (LGG) vs. placebo in elderly subjects receiving Live Attenuated Influenza vaccine (LAIV) (study 2). Healthy elderly volunteers, ages 65-80 were enrolled as outpatients in two clinical studies in which they received the TIV vaccine (study 1, n=28) or the LAIV vaccine (study 2, n=30). In each of the 2 studies, subjects were randomized to receive either LGG capsules containing 1 x 1010 CFU, twice daily for 28 days, or matching placebo capsules twice daily for the same period of time. The study subjects completed a daily diary, telephone calls, and study visits at the Massachusetts General Hospital Clinical Research Centers at baseline, days 21, 28 and 56 and month 5 for the TIV study and baseline, days 21, 28, and 56 for the LAIV study. During each visit, the subject diary, interim history, potential adverse effects and concomitant medications were reviewed and vital signs and a physical examination were performed. Routine blood tests were obtained to monitor for safety during visits and nasopharyngeal and stool samples were collected for microbiome analysis. Volunteers in both studies who were interested in participating in the effect of LGG probiotic on the Human whole Blood Transcriptome substudy also had blood drawn for DNA and RNA extraction, after signing the substudy consent form. The main objectives of the TIV and LAIV studies were to assess the safety and tolerability of 2 x 1010 CFU LGG administered orally to elderly subjects for 28 days after administration of TIV (study 1) or LAIV (study 2). Secondary objectives were to evaluate the richness and microbial diversity in nasopharyngeal and stool specimens using pyrosequencing, and to compare cytokine production in response to bacterial stimulation by following the kinetics of mRNA expression of pro and anti-inflammatory genes and different signaling pathways, in relation to changes in stool Bifidobacterium and Lactobacillus spp. The studies were reviewed and approved by the Partners Human Research Committee (TIV study IRB # 2010p001694 and LAIV study IRB # 2011p002849) and were registered at ClinicalTrials.gov (NCT01368029 and NCT01545349, respectively).

  Study phs000981

• Center for Common Disease Genomics [CCDG] Neuropsychiatric: Autism Spectrum Disorder (ASD) – Whole Exomes

  The National Human Genome Research Institute (NHGRI) has funded a collaborative large-scale genome sequencing effort to comprehensively identify rare risk and protective variants contributing to multiple common disease phenotypes. Called the Centers for Common Disease Genomics (CCDG), this initiative will explore a range of diseases with the ultimate goal of 1) undertaking variant discovery for enough different examples of disease architectures and study designs to better understand the general principles of the genomic architecture underlying common, complex inherited diseases, 2) understanding how best to design rare variant studies for common disease, and 3) developing resources, informatics tools, and innovative approaches and technologies for multiple disease research communities and the wider biomedical research community. The initial focus of the CCDGs will be in cardiovascular disease (early-onset coronary artery disease, atrial fibrillation, hemorrhagic stroke), neuropsychiatric disease (epilepsy, autism), and autoimmune/inflammatory disease (type 1 diabetes, inflammatory bowel disease). The Broad Institute is one of four selected CCDG project centers. The goal of the Autism Spectrum Disorder (ASD) program is to work together to utilize dramatic new advances in DNA sequencing technology to reveal the genetic architecture of autism through comprehensive examination of the exotic sequence of all genes.

  Study phs002502

• Comparison of the treated celiac disease microbiome to that of controls

  Coeliac disease (CeD) is an immune-mediated disorder primarily affecting the small intestine, characterised by an inflammatory immune reaction to dietary gluten. CeD onset results from a multifaceted interplay of genetic and environmental factors. While recent data show that alterations in gut microbiome composition could play an important role, many current studies are constrained by small sample sizes and limited resolution. To address these limitations, we analysed faecal gut microbiota from two Dutch cohorts, CeDNN (128 treated CeD patients (tCeD), 106 controls) and the Lifelines Dutch Microbiome Project (24 self-reported tCeD, 654 controls), using shotgun metagenomic sequencing. Self-reported IBS (570 cases, 1710 controls) and IBD (93 cases, 465 controls) were used as comparative conditions of the gastrointestinal tract. Interindividual variation within the case and control groups was calculated at whole microbiome and strain level. Finally, species-specific gene repertoires were analysed in tCeD patients and controls. Within-individual microbiome diversity was decreased in patients with self-reported IBS and IBD but not in tCeD patients. Each condition displayed a unique microbial pattern and, in addition to confirming previously reported microbiome associations, we identify an increase in the levels of Clostridium sp. CAG:253, Roseburia hominis, and Eggerthella lenta, amongst others. We further show that the observed changes can partially be explained by gluten-free diet adherence. We also observe increased interindividual variation of gut microbiome composition among tCeD patients and a higher bacterial mutation frequency in tCeD that contributes to higher interindividual variation at strain level. In addition, the immotile European subspecies of Eubacterium rectale, which has a distinct carbohydrate metabolism potential, was nearly absent in tCeD patients. Our study sheds light on the complex interplay between the gut microbiome and CeD, revealing increased interindividual variation and strain-level variation in tCeD patients. These findings expand our understanding of the microbiome’s role in intestinal health and disease. Note that some of the data in this study belong to the Lifelines cohort. Access to this dataset can be requested via the page of the EGA data access committee EGAC00001001996. The phenotype data can be requested, for a fee, by filling the application form at https://www.lifelines.nl/researcher/how-to-apply/apply-here.

  Study EGAS50000000959

• The Southern African Human Genome Programme

  The Southern African Human Genome Programme (SAHGP) is a national and regional initiative that aims to unlock the unique genetic character of southern African populations. Its vision is to improve quality of life through understanding human genetic diversity. It is timely to advance the SAHGP initiative since global genomic initiatives are increasingly pointing to populations in Africa, more specifically the San and Khoe from southern Africa, as harbouring the most ancient genetic signatures among the living populations of the world. Studies on African populations have already generated a wealth of information upon which the SAHGP can build. This information will be used to promote and support genomic research programmes both nationally and regionally to address critical questions that would benefit the people of our region. The SAHGP aims to make a significant contribution to the understanding of DNA variation among southern Africans and how this impacts on the health of the people of this region. Aims of the SAHGP: To develop capacity for genomic research in southern Africa; To establish sustainable resources for genomic research in the region; and To translate knowledge and information into improvements in human health in the region. The objective is to derive the maximum benefit from the SAHGP, and that the data should be widely shared with the scientific community for the benefit of the people of the sub-continent and beyond.

  Study EGAS00001002639

• eMERGE Geisinger eGenomic Medicine (GeM) - MyCode Project Controls

  A research cohort of adult Geisinger Clinic patients was enrolled from community-based primary care clinics of the Geisinger Health System. Patients were eligible for enrollment if they were a primary care patient of a Geisinger Clinic physician and were scheduled for a non-emergent clinic visit. All participants provided written informed consent and HIPAA authorization. Consenting patient agreed to provide blood samples for broad biomedical research use, and permission to access data in their Geisinger electronic medical record for research. The enrollment rate was 90% of patients approached. The demographics of the cohort approximate those of the Geisinger Clinic outpatient population. Research blood samples were collected during an outpatient clinical phlebotomy encounter. Research blood samples are coded and stored in a central biorepository. Samples are linkable to clinical data in a de-identified manner for research via an IRB-approved data broker process. For genomic analysis, DNA is extracted from EDTA-anticoagulated whole blood. For the initial eMERGE Geisinger eGenomic Medicine (GeM) genotyping project, a subset of 1,232 unique samples were genotyped using Illumina HumanOmniExpress-12 v1.0 arrays, and used as population controls for other Geisinger Clinic case cohorts, including abdominal aortic aneurysm and gastric bypass surgery cases. These samples were selected from a larger subset of approximately 6,000 MyCode DNA samples using a partial matching algorithm that included age, sex, and body mass index as variables.

  Study phs000381

• Center for Common Disease Genomics [CCDG] - Autoimmune: Inflammatory Bowel Disease (IBD) Exomes and Genomes

  The National Human Genome Research Institute (NHGRI) has funded a collaborative large-scale genome sequencing effort to comprehensively identify rare risk and protective variants contributing to multiple common disease phenotypes. Called the Centers for Common Disease Genomics (CCDG), this initiative will explore a range of diseases with the ultimate goal of: undertaking variant discovery for enough different examples of disease architectures and study designs to better understand the general principles of the genomic architecture underlying common, complex inherited diseases; understanding how best to design rare variant studies for common disease; developing resources, informatics tools, and innovative approaches and technologies for multiple disease research communities and the wider biomedical research community. The initial focus of the CCDGs will be in cardiovascular disease (early-onset coronary artery disease, atrial fibrillation, hemorrhagic stroke), neuropsychiatric disease (epilepsy, autism), and autoimmune/inflammatory disease (type 1 diabetes, inflammatory bowel disease). The Broad Institute is one of four selected CCDG project centers. The overarching aim of the Inflammatory Bowel Disease (IBD) program is to define the full allelic spectrum of protein-altering variation in genes associated to IBD, and assess their role in both Crohn's Disease (CD) and Ulcerative Colitis (UC) risk. The whole genome sequencing data generated here is comprised of samples from US-based diverse populations including African American, Puerto-Rican, Caribean and Cuban origins.

  Study phs001642

• The subclonal architecture of metastatic breast cancer: Results from a prospective community-based rapid autopsy program 'CASCADE'

  Background: Understanding the cancer genome is seen as a key step in improving outcomes for cancer patients. Genomic assays are emerging as a possible avenue to personalised medicine in breast cancer. The majority of work in this area has targeted primary tumours however, and very few studies have performed comprehensive profiling of advanced disease. Evolution of the cancer genome during the natural history of breast cancer is largely unknown, as is the profile of disease at death. We sought to study in detail these aspects of advanced breast cancers that have resulted in lethal disease. Methods and Findings: Three patients with ER-positive, HER2-negative breast cancer and one patient with triple negative breast cancer underwent rapid autopsy as part of an institutional prospective community-based rapid autopsy program. Cases represented a range of management problems in breast cancer, including late relapse after early stage disease; de novo metastatic disease; discordant disease response and disease refractory to treatment. Between 5 and 12 metastatic sites were collected at autopsy together with available primary tumours and longitudinal metastatic biopsies taken during life. Samples underwent paired tumour-normal whole exome sequencing and single nucleotide polymorphism arrays. Subclonal architectures were inferred by jointly analysing all samples from each patient. Mutations were validated using high depth amplicon sequencing.Between cases, there were significant differences in mutational burden, driver mutations, mutational processes and copy number variation. Within each case, we found dramatic heterogeneity in subclonal structure from primary to metastatic disease and between metastatic sites, such that no single lesion captured the breadth of disease. Metastatic cross seeding was found in each case and treatment drove subclonal diversification. Subclones displayed parallel evolution of treatment resistance in some cases, and apparent augmentation of key oncogenic drivers as an alternative resistance mechanism. We also observed the key role of mutational processes in subclonal evolution.Limitations of this study include the potential for bias introduced by joint analysis of formalin fixed archival specimens with fresh specimens, and the difficulties in resolving subclones with whole exome sequencing. Other alterations that could define subclones such as structural variants or epigenetic modifications were not assessed. Conclusions: This study highlights the variety of mechanisms that shape the genome of metastatic breast cancer, and the value of studying advanced disease in detail. Treatment drives significant genomic heterogeneity in breast cancers which has implications for disease monitoring and treatment selection in the personalised medicine paradigm.

  Study EGAS00001002153

• Foregut Microbiome in Development of Esophageal Adenocarcinoma

  The distal esophagus is an important anatomical area where gastric acid reflux can cause reflux esophagitis (RE), Barrett's esophagus (BE) (intestinal metaplasia), and esophageal adenocarcinoma (EA). The incidence of EA has increased 6-fold in the U.S. since the 1970s, parallel to a significant increase in the prevalence of gastroesophageal reflux diseases (GERD). Although specific host factors might predispose one to disease risk, such a rapid increase in incidence must be predominantly environmental. The cause remains unknown. Our hypothesis is that changes in the foregut microbiome are associated with EA and its precursors, RE and BE in the GERD sequence. We will conduct a case control study to characterize the microbiome in every stage of the GERD sequence as well as analyze the trend in changes in the microbiome along disease progression toward EA. Specific Aim 1. To conduct a comprehensive population survey of the foregut microbiome and demonstrate its association with GERD sequence, by a 16S rRNA gene survey. We will analyze samples of the foregut microbiome at three anatomic loci: mouth, distal esophagus, and gastric corpus. Changes of the microbiota in the distal esophagus will be correlated with the phenotypes. Spatial relationship between the esophageal microbiota and upstream (mouth) and downstream (stomach) foregut microbiotas as well as temporal stability of the microbiome-disease association will also be examined. Specific Aim 2. To define distal esophageal metagenome and demonstrate its association with GERD sequence, by shotgun metagenomic analysis. We will first classify samples of the metagenome into metagenotypes by between-sample k-mer distance and correlate the metagenotypes with the four phenotypes. Subsequent detailed analyses will include pathway-disease and gene-disease associations. DNA viruses and fungi, if identified, also will be correlated with the phenotypes. A significant association between the foregut microbiome composition and GERD sequence, if demonstrated, will be the first step for eventually testing the causal hypothesis that an abnormal microbiome is required for the development of the sequence of phenotypic changes toward EA. If EA and its precursors represent a microbial ecological disease, treating the cause of GERD might become possible, for example, by normalizing the microbiome through use of antibiotics, probiotics, or prebiotics. Causative therapy for GERD could prevent its progression and reverse the current trend of increasing incidence of EA.

  Study phs000260

• Providing access to COVID-19 data: one year later

  response efforts On 11 March 2020 the World Health Organization declared the novel coronavirus outbreak a global pandemic. Four months later, the European Genome-phenome Archive (EGA) released its first COVID-19 dataset. This dataset – single cell RNA and VDJ sequencing of B cells from 60 COVID-19 patients – showed that neutralizing antibodies could be identified by high-throughput sequencing in response to SARS-CoV-2 infection. That was one year ago. Today, the EGA provides access to fifteen COVID-19 datasets from researchers across seven countries in Asia, Europe, and North America. These studies represent almost 17,000 individuals and have resulted in at least sixteen publications and preprints. Researchers deposit controlled access COVID-19 data at EGA The global research community has come together rapidly to investigate the SARS-CoV-2 coronavirus and better understand the related disease, COVID-19. These research efforts generate valuable genetic and phenotypic data from patients and research participants that can be shared with approved researchers. The EGA enables sharing of this research data by providing a service for archiving and controlled distribution of sensitive data. Over the past year, the EGA has worked with researchers to archive and distribute COVID-19 data from high-throughput sequencing experiments, genotyping studies, and phenotypic information. These datasets investigate the immune system, blood, and cells and tissues of the lung, which are relevant for studying a contagious respiratory illness caused by a viral infection. *Study Spotlight. In January 2021, Ancestry.com demonstrated the utility of deep phenotyping based on self-reported outcomes from a large population of mild and asymptomatic COVID-19 cases. They identified genetic associations with eight COVID-19 phenotypes and showed distinct patterns of association, most notably related to the chr3/SLC6A20/LZTFL1 and chr9/ABO regions. The supporting data is available at the EGA to approved researchers and includes both genotype and phenotype data for 15,000 individuals. EGA collaborates with global COVID-19 community Since the coronavirus outbreak, the EGA has collaborated with other life science resources to support discovery and access to COVID-19 datasets. COVID-19 Host Genetics Initiative. With the NHGRI’s Genomic Data Science Analysis, Visualization, and Informatics Lab-space (AnVIL) platform, the EGA enables sharing of individual-level genetic and phenotypic data from the COVID-19 Host Genetics Initiative (HGI). This initiative aims to generate, share, and analyze data from COVID-19 host genetics research projects to better understand the genetic determinants of COVID-19 susceptibility, severity, and outcomes. In response to COVID-19, the EGA actively supports COVID-19 data submissions and integration of data access and flow into the COVID-19-HGI analysis platform. *Study Spotlight. The COVID-19 HGI has combined individual-level data for 13,868 COVID-19 positive patients (N=7,167 hospitalized) from 17 cohorts in nine countries. The data were used to assess the association of the major common COVID-19 genetic risk factor (chromosome 3 locus tagged by rs10490770) with mortality, COVID-19-related complications, and laboratory values. The genotype and phenotype data for 10 of these cohorts is available at the EGA to approved researchers under accession EGAS00001005304. Fig 1: EGA COVID-19 studies are searchable in the European COVID-19 Data Portal alongside other COVID-19 and SARS-CoV-2 public datasets. European COVID-19 Data Portal. EGA-archived COVID-19 data are discoverable via the European COVID-19 Data Portal (Fig. 1), which brings together public and controlled access data to accelerate coronavirus research for the international community. By indexing all COVID-19-related data in one place, researchers can more easily discover relevant datasets of interest, thus increasing the “FAIRness” (Findability, Accessibility, Interoperability, Reusability) of this valuable data. Fig 2: SARS-CoV-2 viral sequences are imported from ENA and analysed in Galaxy to detect variants. Results are accessible to researchers through the COVID-19 Viral Beacon. COVID-19 Viral Beacon. The COVID-19 Viral Beacon tool was developed in collaboration with the European Nucleotide Archive and Galaxy to enable near real-time browsing of SARS-CoV-2 variability at genomic, amino acid, and motif levels (Fig. 2). The COVID-19 Viral Beacon allows researchers to (i) perform detailed searches about genomic variants, (ii) filter queries and find unique cases, (iii) filter data based on strain-specific variants, and (iv) explore associated metadata. It uses the Global Alliance for Genomics and Health (GA4GH) Beacon standard including new Beacon v2 features. With this tool, researchers can study intra-host mutations on genomic regions of interest, or trace any variant frequency over time using raw read data. More than 200,000 SARS-CoV-2 analysed genomic data files are now available to researchers for further exploration. Ongoing COVID-19 efforts at EGA Addressing the COVID-19 pandemic is a global effort. Federated resources are necessary to support transnational deposition, access, and analysis of sensitive COVID-19 host genetics and other related data. At the same time, many countries now have emerging personalized medicine programmes which are generating data from national or regional healthcare initiatives. These data are subject to more stringent information governance than research data and often must comply with national data protection legislation. To address this need, the Federated EGA was established to serve as the primary global resource for discovery and access of sensitive human omics and associated data consented for secondary use. The Federated EGA will comprise a network of national human data repositories and will implement community standards and common interfaces. Launching Federated EGA promises to accelerate not only global research efforts to understand, diagnose, and treat COVID-19, but also to foster data reuse, enable reproducibility, and accelerate biomedical and disease research to ultimately improve human health.

  Blog providing-access-to-covid-19

• Development and Use of Network Infrastructure for High-Throughput GWA Studies

  The "Development and Use of Network Infrastructure for High-Throughput GWA Studies" project is collaboration between Group Health Cooperative (GH), the University of Washington (UW), and the Fred Hutchinson Cancer Research Center (FHCRC). It is one of 5 sites participating in The Electronic Medical Records and Genomics (eMERGE) Network funded by the National Human Genome Research Institute (NHGRI) with additional funding from the National Institute of General Medical Sciences (NIGMS). The overall eMERGE project is designed to assess whether linking biorepositories of patients in healthcare delivery systems with electronic medical records (EMRs) is an efficient strategy for high-throughput genome wide association (GWA) studies and whether information can be pooled across sites. The primary phenotype in the Group Health/UW Aging and Dementia eMERGE study project is dementia. Phenotyped participants originated from four population-based sources. Seattle-area members of GH (a large integrated health care system in Washington State) consented and enrolled in 1) the University of Washington Alzheimer's Disease Patient Registry (ADPR) and 2) the Adult Changes in Thought (ACT) study, 3) Marshfield Clinic Personalized Medicine Research Project (PMRP), a population-based DNA, plasma and serum biobank of 20,000 adults, 4) Vanderbilt's BioVU, a de-identified DNA biobank. The ADPR (PI: Eric B. Larson; NIH/NIA U01 AG 006781) is a population-based registry of incident dementia cases designed to identify all new dementia cases within GH from 1987 to 1996. Potential dementia cases were identified through referrals from primary care physicians, mental health services, and neurologists, as well as review of CT scans, neurology, emergency room, geriatrician, and mental health clinic logs, and hospital discharge diagnoses. Medical history, physical, laboratory testing, and neuropsychological testing were performed on all consenting potential cases. These data were reviewed by a consensus conference including a neuropsychologist, study physicians, and an epidemiologist. After discussion of the case, dementia status is assigned using DSM-III-R criteria. Alzheimer's disease status was assigned using the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria. The study base of the ADPR population was stable with an attrition rate of less than 1%/year. The ACT study (PI: Eric B. Larson; NIH/NIA U01 AG 006781) is an ongoing community-based cohort study designed to determine the incidence of Alzheimer's Disease (AD), other types of dementia, and cognitive impairment and to determine risk factors for these conditions. The original cohort of 2,581 was enrolled in 1994-1996. An expansion cohort of 811 was enrolled in 2000-2002. Continuous enrollment to keep 2,000 persons enrolled and at-risk for dementia outcomes was begun in 2005. To date the study has accrued more than 4,000 participants. Dementia-free participants are enrolled in this cohort and evaluated every two years by study personnel with many evaluations including an assessment of cognitive functioning using the Cognitive Abilities Screening Instrument (CASI), which is an extended version of the Mini-Mental State Examination that has been widely used in epidemiological studies of the elderly. Persons with CASI scores lower than 86 or in whom interviewers suspect unusual cognitive decline are followed up with dementia diagnostic evaluations which include physical and neurological examinations and neuropsychological tests. Medical records are reviewed, and laboratory tests and neuroimaging are obtained if not available. The dementia diagnoses and dementia subtypes are determined during a consensus conference attended by the examining clinicians and other study physicians, a neuropsychologist, and research nurse. After discussion of the case, dementia status is assigned using DSM-IV criteria. Alzheimer's disease status was assigned using NINCDS-ADRDA criteria. Individuals diagnosed with dementia are seen again one year following diagnosis using the same procedures. Individuals not diagnosed with dementia are returned to the pool of at-risk individuals and are seen at their next routinely scheduled biennial visit. The ACT sub-sample is stable; for the original cohort, median enrollment in GH was 19 years prior to joining the ACT study, and 85% of the cohort has ≥ 10 years of GH enrollment. DNA for the ADPR participants were obtained through a companion study, Genetic Differences in Cases and Controls (PI: Walter Kukull; NIH/NIA R01 AG007584). DNA obtained through both studies were extracted from blood using Gentra Systems Puregene methods. DNA concentration is determined by UV optical density. All samples are checked for quality by OD 260/280 ratio. For long-term storage, samples are aliquoted and stored at -70°C. The Marshfield study, Personalized Medicine Research Project (PMRP), a population-based DNA, plasma and serum biobank of 20,000 adults. PMRP was started in 2002 as a 3 Phase project. Completed in April 2004, the objectives of Phase I were to build and develop a large population-based biobank with DNA, plasma and serum samples to facilitate genomics research. Phase 1 was also to educate, inform and consult with the Marshfield Epidemiologic Study Area population and communities concerning potential studies, create the DNA foundation of the personalized medicine database and build the bioinformatics tools to store securely and analyze genotypic and phenotypic data. Phase I tasks included operation of the ethics and security advisory board, scientific advisory board and community advisory group. More than 18,000 residents aged 18 and above from 19 different zip codes surrounding Marshfield, WI were invited to participate in Phase I. After providing written informed consent, participants completed brief questionnaires that included questions about demographics, some environmental exposures, family history of disease, and adverse drug reactions, as well as family members living in the area. Participants provided 50ml of blood from which DNA was extracted and plasma and serum samples were stored. The informed consent process allowed access to electronic medical records and included language about non-disclosure of personal research results. A tick-off box was included so that participants could either allow or decline subsequent recontact for future research studied. The objectives of Phase II are to create the phenotypic database, establish the scientific and administrative infrastructure to support genetic mapping of the DNA and the initial discovery projects and genotype a sufficient portion of the genetic material to support these discovery projects. The objectives of Phase III are to expand the discovery projects, complete the genotyping of the genetic database and expand physician/health care provider education and community consultation. The Vanderbilt BioVU model uses discarded blood leftover from clinical care and de-identified clinical information, both of which are tracked with a Research Unique Identifier that is permanently disconnected from the medical record number used to generate it. The Vanderbilt IRB determined that the project does not qualify as "human subject" research under §46.102(f)(1)(2). The program has been reviewed by OHRP twice (the latest immediately prior to launch), and the determination of the Vanderbilt IRB that the project is consistent with the 8/10/2004 guidance has been validated. The model includes a simple opt out mechanism developed for patients who do not wish to have their samples included. Planning (including community involvement, ethics and IRB discussions, focus groups, development of operating procedures and pilot studies to assess them) began in May 2004, and the resource commenced sample collection in February 2007 and as of May 2009 contains approximately 56,000 samples. The current resource will be available to all Vanderbilt investigators who sign a Data Use Agreement. The resource represents Vanderbilt's broad patient population and thus provides a potential resource for research in a range of common and rare diseases as well as drug response or medication safety. BioVU patient protection model: There has been extensive involvement by the ethics community and the IRB to put in place procedures to provide privacy protection. The overall protection plan is multifaceted and includes a combination of technology and policy: (1) creation of the SD described above; (2) return of only the specific clinical data items requested by investigators (rather than the complete de-identified chart); (3) submission of any specific proposed project to the IRB and to a separate protocol review committee, both of which must approve; (4) implementing a Data Use Agreement that permits only approved queries and data analyses, specifically prohibits attempts at re-identification (at the risk of institutional sanctions), and mandates redeposit of all genetic information generated in a research study back into a genomic database; and (5) tracking and auditing all use.

  Study phs000234

• Columbia University Study of Caribbean Hispanics with Familial and Sporadic Late Onset Alzheimer's disease

  Compared to Caucasians residing in the same community the incidence rate of Alzheimer's disease is approximately twice as high in Caribbean Hispanics. Moreover, Caribbean Hispanics represent a homogenous population with only a few founders. Replication of genetic associations in other ethnic groups provides supporting evidence that a putative gene is involved in the disease pathogenesis, and when different allelic variants within the same genes are associated with disease it can help to localize the pathogenic variant. SORL1 is an example of a candidate gene that was first identified in Hispanics and then confirmed in multiple ethnic and racial groups in a meta-analysis. For this project, we are genotyping 704 individuals in families multiply affected by Alzheimer's disease (166 families). These families were recruited in the United States, Puerto Rico and the Dominican Republic. In addition, we are genotyping 2491 individuals (960 patients with sporadic Alzheimer's disease and 1531 unrelated controls) phenotyped in a similar fashion totaling 3195 individuals. Both cohorts are followed at regular intervals of 18 to 24 months, and potential phenotypes available other than those related to Alzheimer's disease include body mass index, measured blood pressure, neurological history and examinations. More importantly, both studies are funded through 2014 and additional phenotypes could be added in successive waves. We propose a genome wide association (GWA) study of Alzheimer's disease and longitudinal changes in cognition and other age-related neurological and medical phenotypes. The goal will be to identify the chromosomal locations of genes underlying this disease and its related endophenotypes.

  Study phs000496

• The Oral Microbiome and Head and Neck Cancer

  Oral microbiota may influence head and neck squamous cell carcinoma (HNSCC) development, potentially related to carcinogen metabolism. The human oral cavity hosts a diverse microbiota, including bacteria and fungi. We performed shotgun sequencing and ITS1 sequencing on 236 HNSCC case participants who developed HNSCC during a mean follow-up of 5.1 years and 458 matched controls who remained HNSCC-free. Oral samples were obtained from a prospective nested case-control study within three epidemiological cohorts: the American Cancer Society Cancer Prevention Study II Nutrition Cohort (ACS CPS-II), the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO), and the Southern Community Cohort Study (SCCS). Control participants were selected using 2:1 frequency matching based on cohort, age, sex, race and ethnicity, and time since oral sample collection.

  Study phs004018

• Toxigenic Clostridium perfringens isolated from at-risk pediatric inflammatory bowel disease patients

  With the goal of studying mucosal-associated bacteria and products detrimental to inflammatory bowel disease (IBD) patients, we directly cultured bacterial communities from mucosal biopsies and examined for detrimental traits. Focusing on red blood cell lysis, a virulence trait, communities from 5 of 9 patients exhibited hemolytic activity. Clostridium perfringens was isolated from each hemolytic community, and whole-genome sequencing confirmed presence of hemolytic toxins – alpha toxin in all 5 strains, perfringolysin O (PFO) in 4 strains, alveolysin in 2 strains – and absence of enterotoxins. In vitro cytotoxicity experiments demonstrated strain supernatants were toxic to various cell types located beneath the intestinal epithelial barrier, including endothelial, neuroblasts, and neutrophils, while impact on epithelial cells was less pronounced. These findings suggest C. perfringens may be damaging particularly when intestinal barrier integrity is compromised, such as in IBD patients. Further characterization using purified toxins and genetic insertion mutants confirmed PFO toxin was sufficient for cell toxicity. C. perfringens supernatants also induced activation of neuroblast and dorsal root ganglion (DRG) neuron cells in vitro, suggesting C. perfringens in inflamed mucosal tissue may directly contribute to abdominal pain, a frequent IBD symptom. Strikingly, C. perfringens was detected in biopsies of 8 of 9 pediatric patients while not in all corresponding stool samples, and in other datasets, C. perfringens was in stool samples of IBD adults (18.7-27.1%) much more frequently versus healthy (5.1%). Our findings showcase C. perfringens may have an important pathogenic impact on IBD patients. Similar to Clostridioides difficile, routine monitoring of C. perfringens and PFO toxins in patients may be beneficial.

  Study EGAS50000000334

• CIDR, NCI, NIDA Sequencing of Targeted Genomic Regions Associated with Smoking

  This study includes samples from two projects: Collaborative Genetic Study of Nicotine Dependence (COGEND; PI: Laura Bierut) and Genetic Study of Nicotine Dependence in African Americans (AAND; PI: Laura Bierut and Eric Johnson). The majority of the COGEND subjects included in the current study overlap with the two datasets already available on dbGaP. GWAS data are available for COGEND subjects through the Study of Addiction: Genetics and Environment (SAGE), dbGaP study accession phs000092. It should be noted that the case definition in the SAGE study is DSM-IV alcohol dependence. GWAS data are available for additional COGEND subjects through The Genetic Architecture of Smoking and Smoking Cessation, dbGaP study accession phs000404. The overall goal of this project is to apply deep sequencing to key genomic regions associated with nicotine dependence in order to accelerate the discovery of variation in molecular pathways that govern the development of nicotine dependence. The sample includes unrelated cases and controls of European American and African American descent. Cases are defined by a commonly used definition of nicotine dependence, a current score of 4 or more (maximum score of 10) on the Fagerstrom Test for Nicotine Dependence (FTND). Control status is defined as an individual who smoked at least 100 cigarettes during their lifetime, yet never became dependent (lifetime FTND<2). By selecting controls who smoked cigarettes, we focus on those genetic effects that are specific to the development of nicotine dependence. COGEND: COGEND was initiated in 2001 as a three-part program project grant funded through the National Cancer Institute (NCI; PI: Laura Bierut). The three projects included a study of the familial transmission of nicotine dependence, a genetic study of nicotine dependence, and a study of the relationship of nicotine dependence with nicotine metabolism. The primary goal was to detect, localize, and characterize genes that predispose or protect an individual with respect to heavy tobacco consumption, nicotine dependence, and related phenotypes and to integrate these findings with the family transmission and nicotine metabolism findings. The primary design was a community based case-control study. Nicotine dependent cases and non-dependent, smoking controls were identified and recruited from Detroit and St. Louis. More than 54,000 subjects aged 25-44 years were screened by telephone; more than 3,100 subjects were personally interviewed; and more than 2,900 subjects donated blood samples for genetic studies. AAND: AAND was initiated in 2009 to identify and characterize genetic determinants of nicotine dependence in a large African American population. Community-based recruitment of approximately 100,000 people was conducted to ascertain 1,000 African American nicotine dependent cases and 1,000 African American non-dependent, smoking controls. All subjects were between the ages of 25-44. Subjects were screened by telephone; if they qualified as a case or control, they completed the same interview that was used in COGEND and donated a blood sample. Both studies (COGEND and AAND) included measures of basic socio-demographic variables, including age, sex, race/ethnicity, family income, and educational attainment using the Semi-Structured Assessment for the Genetics of Nicotine Dependence. Information on nicotine dependence, as assessed by the Fagerstrom Test for Nicotine Dependence (FTND) is available for all subjects. In addition, participants also completed the Nicotine Dependence Syndrome Scale (NDSS; Shiffman et al., 2004) and the Wisconsin Inventory of Smoking Dependence Motives (WISDM-68; Piper et al, 2004). All subjects were assessed in person by trained research assistants.

  Study phs000813

• Puerto Rico Heart Health Program (PRHHP-BioLINCC)

  Data Access NOTE: Please refer to the “Authorized Access” section below for information about how access to the data from this accession differs from many other dbGaP accessions. Objectives: To investigate morbidity and mortality from Coronary Heart Disease (CHD) in Puerto Rican rural and urban men. The objectives of the study were: (1) to identify factors related to the development of CHD, (2) compare the etiology of disease in rural versus urban men, and (3) determine the prevalence and incidence of CHD and other cardiovascular diseases in Puerto Rican males.Background: As Puerto Rico became more industrialized in the 1940s and 1950s, mortality rates for CHD increased. Since many factors related to CHD can be relatively homogenous within a population, two contrasting subgroups were selected for study in Puerto Rico: a rural population of men from a mountainous community and an urban population selected from San Juan. The NHLBI initiated the Puerto Rico Heart Health Program in May, 1965 as a prospective study of lifestyle, environmental and biological factors in the progression of cardiovascular disease in Puerto Rican men.Participants: A total of 9,824 (2,976 rural, 6,848 urban) men, age 45 to 64 were examined at the baseline exam.Design: The examination consisted of standardized questionnaires to determine education, occupation, smoking habits, and physical activity. Trained interviewers conducted a nutritional survey through a 24 hour diet recall. Subjects were also examined to determine prevalent cardiovascular, cerebrovascular and peripheral vascular abnormalities. The examination included vital capacity, a 12-lead ECG, and laboratory tests for hematocrit, glucose, serum cholesterol, serum glycercides and lipoprotein electrophoresis. A medical history was also obtained. Three additional exams, approximately three years apart, were conducted and morbidity and mortality follow-up concluded in 1980.

  Study phs003930

• An analysis of humoral and cellular immune responses following COVID-19 vaccination.

  Two dose mRNA vaccination provides excellent protection against SARS-CoV-2. However, there are few data on vaccine efficacy in elderly individuals above the age of 801. Additionally, new variants of concern (VOC) with reduced sensitivity to neutralising antibodies have raised fears for vulnerable groups. Here we assessed humoral and cellular immune responses following vaccination with mRNA vaccine BNT162b22 in elderly participants prospectively recruited from the community and younger health care workers. Median age was 72 years and 51% were females amongst 140 participants. Neutralising antibody responses after the first vaccine dose diminished with increasing age, with a steep drop in participants over 80 years old. Sera from participants below and above 80 showed significantly lower neutralisation potency against B.1.1.7, B.1.351 and P.1. variants of concern as compared to wild type. Those over 80 were more likely to lack any neutralisation against VOC compared younger participants following first dose. Binding IgG and IgA antibodies were lower in the elderly, as was the frequency of SARS-CoV-2 Spike specific B- cells. We observed a trend towards lower somatic hypermutation in participants with suboptimal neutralisation, and elderly participants demonstrated clear reduction in class switched somatic hypermutation, driven by the IgA1/2 isotype. SARS-CoV-2 Spike specific T- cell IFN?? and IL-2 responses were secreted primarily by CD4 T cells, and impaired in the older age group. We conclude that the elderly are a high risk population that warrant specific measures in order to mitigate against vaccine failure, particularly where variants of concern are circulating. Specifically, the dosing interval should not be extended in this group.

  Study EGAS00001005380

• Lung Cancer Genetic Study Among Asian Never Smokers

  The Lung Cancer Genetic Study Among Asian Never Smokers includes data from four population-based studies conducted among Asian women: the Shanghai Women's Health Study (SWHS), the Hwasun Cancer Epidemiology Study (HCES1 and HCES2), the Female Lung Cancer Consortium in Asia (FLCCA, including sFLCA), and the Guangzhou Lung Cancer Study (GLCS). Shanghai Women's Health Study (SWHS): The SWHS is a population-based prospective cohort study of approximately 75,000 adult women who were recruited between 1997 and 2000. The cohort has been followed by a combination of record linkage and active follow-ups. Lung cancer patients identified in the SWHS and non-cases were included in the current study.Hwasun Cancer Epidemiology Study-Lung Cancer (HCES1 and HCES2): The HCES is a hospital-based case-control study whose goal is to identify factors of the cancer development and clinical progression in a Korean population. Included in this project were 299 female lung cancer cases from HCES2, who were diagnosed between April 2004 and February 2013 at Chonnam National University Hwasun Hospital, a cancer specified hospital in Jeollanam-do province, South Korea. Controls were randomly selected from women with no previous cancer diagnosis at enrollment in the Namwon Study and the Dong-gu study, ongoing community-based cohort studies in South Korea. A total of 1,103 controls (273 from HCES1 and 830 from HCES2) were genotyped by MEGA. Guangzhou Lung Cancer Study (GLCS): The GLCS is a case-control study including never-smoking women lung cancer cases and controls from Guangzhou, China.In this study, the DNA samples of 1,195 subjects from SWHS and GLCS were genotyped using whole exome sequencing (WES), and the DNA samples of 7,174 subjects from SWHS, HCES1, HCES2, FLCCA, and sFLCA were genotyped using the Multi-Ethnic Global Array (MEGA).

  Study phs002366

• Integrated Epigenetic Maps of Human Embryonic, Extraembryonic and Adult Cells

  Working cooperatively with other Mapping Centers and the Data Coordination Center (EDACC) funded by this Roadmap mechanism we have comprehensively mapped the epigenomes of select human cells with significant relevance to complex human disease. Our effort has been focused on cells relevant to human health and complex disease including cells from the blood, brain, breast, skin, male germ cells, extraembryonic tissues and trophoblast, and U.S. Government-approved lines of human embryonic stem cells. We have incorporated high quality, homogeneous cells from males and females, and two predominant racial groups, and biological replicates of each cell type. The resulting comprehensive maps include up to 6 histone modifications selected for their opposing roles in regulating active and inactive chromatin (H3K4me1, H3K4me3, H3K9me3, H3K9ac, H3K27ac, H3K27me3, H3K36me3), DNA methylation, miRNA and gene expression, and for select cases whole genome shotgun sequence. Our cell and data production pipeline incorporates verification and data validation with independent methods, and operates under a model motivated by increased data production and decrease cost. Our group in conjunction with the other REMC teams, the EDACC, ENCODE, Epigenetics of Human Health and Disease centers and the NIH Roadmap program are developing methods, tools and reference epigenome maps for the research community that will make the promise of epigenetics in understand and treating human complex disease a reality. Our reference epigenomes will enable new disciplines including human population epigenetics, comparative epigenomics, neuroepigenetics, and therapeutic epigenetics for tissue regeneration and reversal of disease.

  Study phs000791

• NHLBI GO-ESP Family Studies: Idiopathic Bronchiectasis of unknown etiology that is not related to cystic fibrosis or classic primary ciliary dyskinesia or immune deficiency or any other known causes

  The NHLBI "Grand Opportunity" Exome Sequencing Project (GO-ESP), a signature project of the NHLBI Recovery Act investment, was designed to identify genetic variants in coding regions (exons) of the human genome (the "exome") that are associated with heart, lung and blood diseases. These and related diseases that are of high impact to public health and individuals from diverse racial and ethnic groups will be studied. These data may help researchers understand the causes of disease, contributing to better ways to prevent, diagnose, and treat diseases, as well as determine whether to tailor prevention and treatments to specific populations. This could lead to more effective treatments and reduce the likelihood of side effects. GO-ESP is comprised of five collaborative components: 3 cohort consortia - HeartGO, LungGO, and WHISP - and 2 sequencing centers - BroadGO and SeattleGO. The major goal of this project is to apply next generation resequencing technology to identify disease-causing variants that cause bronchiectasis of unknown etiology (e.g. non cystic fibrosis (CF), classic primary ciliary dyskinesia (PCD), immune deficiency, or any other known cause of bronchiectasis), i.e., "idiopathic bronchiectasis." As part of our ongoing efforts to define the genetic cause of rare lung diseases, we have also studied families in whom diagnosis of PCD or other known etiologies could not be confirmed. We have systematically collected and stored the DNA and phenotypic data on each of the families in our cohort. The phenotypic data includes age, gender, ethnicity information, clinical data pertaining to the airways disease, including neonatal respiratory distress, otitis media, sinusitis and bronchiectasis, ciliary ultrastructure analysis, and microbial colonization (status of nontuberculosis mycobacterium). During the course of our study, we have acquired 98 unrelated patients in whom bronchiectasis seemed to be of unknown causes. We will be using 11 unrelated patients, 5 unrelated affected sib-pairs, and 3 affected sibs from a family from this cohort, based on 1) development of bronchiectasis in the absence of smoking, 2) a good family pedigree with available DNA, and 3) a family history of bronchiectasis and/or occurrence of airways disease in a sibling. Classic CF, PCD and immune deficiency were ruled out, based on the tests described above. Alpha-1 antiprotease deficiency work up was negative and none of the patients were tobacco users or smokers.

  Study phs000518

• eMERGE III: Columbia GENIE (Genomic Integration with EHR)

  The Columbia GENIE study contributes and shares phenotype and genotype data for individuals who were treated with our healthcare facilities and consented to share their data with dbGaP for scientific discovery. Some of these individuals have kidney or neurological problems and some are healthy volunteers from the Washington Height patient community. The purpose of this NOMAS study is to obtain information about physical features of the brain, carotid arteries, and heart. Some of our patients are pediatric patients with cardiac conditions. The study sample consists of four patient cohorts: Northern Manhattan Study (NOMAS), N=1072 Pediatric Cardiac Genomic Consortium (PCGC), n=374 Caribbean Hispanics with Familial and Sporadic Late Onset Alzheimer's disease (Caribbean Hispanics/AD), n=330 Alzheimer's Disease Sequencing Project (ADSP, n=44) Genetics of Chronic Kidney Disease Study, n=1256

  Study phs000961

• Exome sequencing of UK Birth Cohorts - Born in Bradford

  Birth cohort studies involve repeated surveys of large numbers of individuals from birth and throughout their lives. They collect information useful for a wide range of life course research domains, and biological samples which can be used to derive data from an increasing collection of omic technologies. This rich source of longitudinal data, when combined with genomic data, offers the scientific community valuable insights from population genetics to rare disease associations. Avon Longitudinal Study of Parents and Children (ALSPAC)recruited 14,775 babies of predominantly White ethnicity in the Avon county of south-west England between 1991 and 1992. Born in Bradford (BiB) is similarly focused on a particular local area, the city of Bradford in the north of England, and recruited 13,858 babies between 2007 and 2011, of whom ~41% self-report as white British and ~59% as other ethnicities, predominantly Pakistani. Millennium Cohort Study (MCS) is a national cohort that recruited 18,827 children born between 2000 and 2002, intentionally over-sampling areas with high child poverty, large ethnic minority populations, and smaller UK nations (Wales, Scotland and Northern Ireland) Available here is a subset of exome-sequenced parents and children from these studies (CRAMS and post-QC VCFs) as detailed in https://doi.org/10.12688/wellcomeopenres.22697 [doi.org]. Phenotypic data is also available by submitting an application to the corresponding cohort: https://borninbradford.nhs.uk/ [borninbradford.nhs.uk]

  Dataset EGAD00001015370

• Study of Osteoporotic Fractures (SOF)

  The Study of Osteoporotic Fractures (SOF) is a prospective multicenter study of risk factors for vertebral and non vertebral fractures. The cohort is comprised of 9704 community-dwelling women 65 years old or older recruited from populations-based listings in four U.S. areas: Baltimore, Maryland; Minneapolis, Minnesota; Portland, Oregon; and the Monongahela Valley, Pennsylvania. Women enrolled in the study were 99% Caucasian with African American women initially excluded from the study due to their low incidence of hip fractures. (A cohort of AA women was recruited at the 6th Visit.) The SOF participants were followed up every four months by postcard or telephone to ascertain the occurrence of falls, fractures and changes in address. To date, follow-up rates have exceeded 95% for vital status and fractures. All fractures are validated by x-ray reports or in the case of most hip fractures, a review of pre-operative radiographs. Blood samples were collected in 6795 women at their Year 2 exam (Visit 2) and with written consent for use of DNA in genetic studies. Of these, we have GWAS data on 3625 Caucasian participants. As a separate study, the SOF Osteoarthritis Project was funded separately to collect data about risk factors for osteoarthritis (OA) and analyze baseline hip and hand films for the presence and severity of OA. Raw GWAS data is housed at the study's coordinating center and not released as part of the dbGaP release. The raw data can be requested from the study's coordinating center. Only QC cleaned PLINK files are available at dbGaP. Auxiliary files are also available for duplicates and HapMap participants.

  Study phs000510

• Deep single-cell RNA sequencing data for 12346 T cells from tumour, adjacent normal tissue and peripheral blood of treatment-naive NSCLC patients

  Cancer immunotherapies have shown sustained clinical responses in treating non-small cell lung cancer (NSCLC), but efficacy varies between patients and is believed to depend in part on the amount and properties of tumor infiltrating lymphocytes (TILs). To comprehensively depict and dissect the baseline landscape of the composition, lineage and functional states of TILs in lung cancer, here we generated deep single-cell RNA sequencing data for 12,346 T cells from the primary tumour, adjacent normal tissues and peripheral blood of 14 treatment-naive NSCLC patients. Combined expression and TCR-based lineage tracking revealed a significant proportion of effector T cells with common origins and similar functional states across peripheral blood and tumours pointing towards a highly migratory nature of these T cells. We also observed tumour-infiltrating CD8+ T cells undergoing extensive clonal expansion and exhaustion, with two clusters of cells exhibiting states preceding exhaustion. Survival analysis on independent datasets suggested that high ratio of pre-exhausted to exhausted T cells is associated with better prognosis of lung adenocarcinoma (LUAD). In addition, we observed further heterogeneity within the tumour regulatory T cells (Tregs), characterized by the bimodal distribution of TNFRSF9, an activation marker for antigen-specific Tregs. The gene signature of this group of activated tumour Tregs, which included IL1R2, correlated with poor prognosis in LUAD. The T cell clusters revealed by our single cell analyses provide a new approach for patient stratification, and the accompanying compendium of data will help the research community to gain further insight into the functional states and dynamics of T cell responses in lung cancer.

  Study EGAS00001002430

• A somatic reference standard for cancer genome sequencing.

  Paired PCR-free whole genome sequencing data of a matched metastatic melanoma cell line (COLO829) and normal across three lineages and across separate institutions, with independent library preparations, sequencing, and analysis. The data was generated with mean mapped coverages of 99X for COLO829 and 103X for the paired normal across three institutions. Overall, common events include >35,000 point mutations, 446 small insertion/deletions, and >6,000 genes affected by copy number changes. We present this reference to the community as an initial standard for enabling quantitative evaluation of somatic mutation pipelines across institutions.

  Dataset EGAD00001002142

• GEDI: A Developmental Model of Gene-Environment Interplay in SUDs: Combined Genotype Dataset from the "Great Smoky Mountains Study" and the "Caring for Children in the Community Study".

  1. Great Smoky Mountains Study (GSMS; Costello et al. 1996, 1997) Three cohorts of boys and girls, aged 9, 11, and 13 years at intake in 1993, were selected from a rural population of some 20,000 children using a household equal probability design. A two-phase procedure was used for White and African-American youth to increase power by oversampling children at risk for psychiatric and SUDs. Parents (usually mothers) of the first stage random population sample completed a questionnaire about their child's behavioral problems. Of 4,195 subjects selected, 95% (N=3,896) of parents completed the screen. All children scoring above a predetermined threshold (the top 25% of the total scores), plus a 10% random sample of the remaining 75%, were recruited for detailed interviews. Results can be back-weighted to population levels for analyses. Half of the sample consists of females, and 6% are African Americans, reflecting the population of the study area. The interviewed sample of white and African-American subjects was 1,070 (80% of those recruited). American Indian youth were oversampled (100%) because they are an understudied group known to be at high risk for stressful events, substance disorders, and mood disorders. Of 431 age-eligible children, 350 (81% boys, 49% girls) participated. Thus, the size of total GSMS sample is 1,070 + 350 = 1,420. Data collection is complete for ages 9-26, and age 30 interviews are in progress. By age 26 a total of 9,858 interviews had been completed; the average number of interviews per subject was seven, and by age 26, 97.3% completed two or more interviews. 2. The Caring for Children in the Community Study (CCC; Angold et al., 2002) This representative study of psychiatric illness and service use in African-American and White youth took place in four rural counties in the southeastern USA. The two-stage sampling design and methods are similar to those used in the GSMS. Of 4,500 youth randomly selected from the 17,117 9- to 17-year-olds in the public school's database, 3,613 (80.0%) were successfully contacted and agreed to complete the behavioral screen. Of the 1,302 selected to participate in the study, 920 (70.7%) interviews were completed. Because CCC was also the only study in GEDI to contain more than a very few African-American participants, these were omitted from the multi-site analyses. Reprinted with permission from Cambridge University Press from Costello et al., 2013: PMID: 23461817 References: Costello et al., 1996: PMID: 8956679 Costello et al., 1997: PMID: 9184514 Angold et al., 2002: PMID: 12365876

  Study phs000852

• Advancing Precision Oncology in a Humanized, Fully Autologous Mouse Model

  Progress in the early detection and treatment of cancer requires accurate model systems to further evaluate new, promising discoveries. Small animal and, in particular, mouse model systems are attractive to researchers for numerous reasons, including their ease of use and well-described platforms. The ability to grow human tumors in immune-deficient mice (so-called patient-derived xenografts, or PDXs) allows researchers to work directly with human cancer tissue in a controlled setting. However, PDX models are limited by their lack of an intact immune system. Immunotherapy has revolutionized clinical oncology, but lacks pre-clinical models of the human immune system and human cancer to investigate new modalities and limitations/toxicities of treatment regimens. The broad objective of this study is to validate an in vivo model to evaluate human tumors in the context of a complete and intact human immune system in a completely personalized and autologous fashion to study cancer immunotherapy. Herein, we will: (1) validate the ability of our humanized system to serve as a model for cancer immunotherapy treatment response and toxicity in patients with melanoma, including immunotherapy checkpoint blockade and vaccine strategies, and (2) extend our current work in melanoma by validating the ability to establish humanized mice and evaluate tumor growth and leukocyte development in autologous human pancreatic and colorectal tumors established in humanized mice. In each of these areas, we will leverage our multi-institutional team's individual expertise along with our institutional infrastructure to maximize the success of the experimental aims. The results from this project will be widely available to the general research community for future, hypothesis-driven research. Taken together, our study will meet multiple goals and address several unmet needs in cancer immunotherapy, thus significantly enhancing the applicability of a fully autologous and immunocompetent precision model system for use in translational oncology research.

  Study phs003090

• Gabriella Miller Kids First Pediatric Research Project in Microtia in Hispanic Populations

  The Gabriella Miller Kids First Pediatric Research Program (Kids First) is a trans-NIH effort initiated in response to the 2014 Gabriella Miller Kids First Research Act and supported by the NIH Common Fund. This program focuses on gene discovery in pediatric cancers and structural birth defects and the development of the Gabriella Miller Kids First Pediatric Data Resource (Kids First Data Resource). All of the WGS and phenotypic data from this study are accessible through dbGaP and kidsfirstdrc.org, where other Kids First datasets can also be accessed. Microtia is a rare congenital deformity of the external ear, the pinna. The severity of microtia is variable and ranges from subtle deformities in the pinna to absence of the external ear. Microtia is often associated with closure of the external auditory ear canal causing significant hearing loss. Microtia can be an isolated, unilateral or bilateral malformation, or occur solely with ear canal deformities, or with additional craniofacial or syndromic manifestations. Earlier studies of identical twins with microtia demonstrated a significant genetic contribution. The molecular pathogenesis for most microtia remains unknown. We propose to leverage our clinical acumen in diagnosis and treatment of microtia (R.E.), our relationship to the microtia community (M.T.) and our collected DNA samples from microtia patients to identify genetic variant(s) that contribute to this congenital malformation. Microtia prevalence is much higher among Native Americans and some Latin Americans (17 per 10000 Ecuadorian births) than among individuals of European-descent (0.6 -1.6 per 10,000 births). To capitalize on this epidemiologic data, we have recruited microtia cohorts from Latin America and the U.S, including clinical data and DNA samples.

  Study phs002172

• HeLa Cell Genome Sequencing Studies

  HeLa is a human epithelial adenocarcinoma cell line that was derived from biopsy specimens of a 31-year old patient named Henrietta Lacks who was being treated for cervical cancer at The Johns Hopkins University Hospital in 1951. The specimens were obtained without her knowledge or consent just before her death in 1951. HeLa is the oldest and most widely used human cell line and has been an extraordinarily important resource for researchers throughout the world. HeLa cells have served as a standard for understanding many fundamental biological processes, such as testing the polio vaccine, establishing basic techniques for cloning and in vitro fertilization, identifying the cause of cervical cancer (HPV), and advancing the development of anti-cancer drugs.This study contains all authorized whole genome sequence data of the HeLa cell line from datasets currently in dbGaP. These data have been approved for health, medical, and/or biomedical research purposes. Access to these data can be granted for one year. Accessible data will include the studies listed on this page and any additional authorized datasets that become available during this one-year period. The HeLa Genome Data Access Working Group of the Advisory Committee to the Director (ACD) will review requests from the research community for access to these datasets and assess whether the requests align with the terms of use defined in the HeLa Genome Data Use Agreement. The Working Group's findings will be reported to the ACD, and the ACD will make recommendations to the NIH Director about whether a request should be approved or disapproved. The NIH Director will decide whether access to the data will be granted.

  Study phs000640

• Metagenomic Epidemiology of Antibiotic Resistance in Infectious Diarrhea

  The study of antimicrobial resistance (AMR) in infectious diarrhea has generally been limited to cultivation, antimicrobial susceptibility testing and targeted PCR assays. When individual strains of significance are identified, whole genome shotgun (WGS) sequencing of important clones and clades is performed. Genes that encode resistance to antibiotics have been detected in environmental, insect, human and animal metagenomes and are known as "resistomes". While metagenomic datasets have been mined to characterize the healthy human gut resistome in the Human Microbiome Project and MetaHIT and in a Yanomani Amerindian cohort, directed metagenomic sequencing has not been used to examine the epidemiology of AMR. Especially in developing countries where sanitation is poor, diarrhea and enteric pathogens likely serve to disseminate antibiotic resistance elements of clinical significance. Unregulated use of antibiotics further exacerbates the problem by selection for acquisition of resistance. This is exemplified by recent reports of multiple antibiotic resistance in Shigella strains in India, in Escherichia coli in India and Pakistan, and in nontyphoidal Salmonella (NTS) in South-East Asia. We propose to use deep metagenomic sequencing and genome level assembly to study the epidemiology of AMR in stools of children suffering from diarrhea. Here the epidemiology component will be surveillance and analysis of the microbial composition (to the bacterial species/strain level where possible) and its constituent antimicrobial resistance genetic elements (such as plasmids, integrons, transposons and other mobile genetic elements, or MGEs) in samples from a cohort where diarrhea is prevalent and antibiotic exposure is endemic. The goal will be to assess whether consortia of specific mobile antimicrobial resistance elements associate with species/strains and whether their presence is enhanced or amplified in diarrheal microbiomes and in the presence of antibiotic exposure. This work could potentially identify clonal complexes of organisms and MGEs with enhanced resistance and the potential to transfer this resistance to other enteric pathogens. We have performed WGS, metagenomic assembly and gene/protein mapping to examine and characterize the types of AMR genes and transfer elements (transposons, integrons, bacteriophage, plasmids) and their distribution in bacterial species and strains assembled from DNA isolated from diarrheal and non-diarrheal stools. The samples were acquired from a cohort of pediatric patients and controls from Colombia, South America where antibiotic use is prevalent. As a control, the distribution and abundance of AMR genes can be compared to published studies where resistome gene lists from healthy cohort sequences were compiled. Our approach is more epidemiologic in nature, as we plan to identify and catalogue antimicrobial elements on MGEs capable of spread through a local population and further we will, where possible, link mobile antimicrobial resistance elements with specific strains within the population.

  Study phs001260

• Somatic Mutations and Their Etiological Determinants for Breast Cancer in African American Women (B-CAUSE Study)

  The breast cancer health disparity between women of African ancestry (AA) and European ancestry (EA) remains a major public health challenge in the United States. AA women are afflicted by higher rate of triple-negative breast cancer (TNBC) and bear the highest mortality rate of all populations from the disease. Even within TNBC, some data suggest that AA women have poorer outcomes than EA women. Mounting evidence points to population differences in cancer biology, a fundamental question that remains unsettled. The disparity also manifests in representativeness in tumor sequencing projects, due to the low inclusion of AAs in genomic studies. A recent analysis of The Cancer Genome Atlas (TCGA) data revealed that the number of AA cases sequenced was sufficient only for studying frequently mutated genes (≥10%), and the power was worse for TNBC as a separate disease entity. As a result, the breast tumor mutational landscape elucidated to date is derived mostly from EA cases, and may not necessarily represent AA cancer genomes. Moreover, as discovery potential for new driver genes has come close to a plateau, cancer in AAs derived from distinct genetic and environmental contexts may provide a powerful venue for discovering mutations that are rare in EA cases. This is showcased in recent studies in colon and prostate cancer. Thus, we carried out a collaborative project, B-CAUSE, to characterize the mutational landscape of AA breast cancer genomes by pooling resources from five established studies, including the Women's Circle of Health Study (WCHS), the Black Women's Health Study (BWHS), the Southern Community Cohort Study (SCCS), the Nashville Breast Health Study (NBHS), and the Southern Tri-State Breast Health Study (STSBHS). This effort has created the largest AA-specific breast tumor mutation dataset to date in an efficient manner. The data deposited here are from the whole-exome sequencing (WES) of matched tumor-normal pairs of 462 TNBC in AA women from the B-CAUSE Study.

  Study phs003962

• First genome-wide association study in an Australian Aboriginal population provides insights into genetic risk factors for Body Mass Index and Type 2 Diabetes

  A body mass index (BMI) >22kg/m2 is a risk factor for type 2 diabetes (T2D) in Aboriginal Australians. To identify loci associated with BMI and T2D we undertook a genome-wide association study using 1,355,133 quality-controlled single nucleotide polymorphisms (SNPs) genotyped (Illumina 2.5M Duo Beadchip) in 402 individuals in extended pedigrees from a Western Australian Aboriginal community. Imputation using the thousand genomes (1000G) reference panel extended the analysis to 6,724,284 post quality-control autosomal SNPs. No associations achieved genome-wide significance, commonly accepted as P<5x10-8. Nevertheless, genes/pathways in common with other ethnicities were identified despite the arrival of Aboriginal people in Australia >45,000 years ago. The top hit (rs10868204 Pgenotyped=1.50x10-6; rs11140653 Pimputed_1000G=2.90x10-7) for BMI lies 5’ of NTRK2, the type 2 neurotrophic tyrosine kinase receptor for brain-derived neurotrophic factor (BDNF) that regulates energy balance downstream of melanocortin-4 receptor (MC4R). PIK3C2G (rs12816270 Pgenotyped=8.06x10-6; rs10841048 Pimputed_1000G=6.28x10-7) was associated with BMI, but not with T2D as reported elsewhere. BMI also associated with CNTNAP2 (rs6960319 Pgenotyped=4.65x10-5; rs13225016 Pimputed_1000G=6.57x10-5), previously identified as the strongest gene-by-environment interaction for BMI in African-Americans. The top hit (rs11240074 Pgenotyped=5.59x10-6, Pimputed_1000G=5.73x10-6) for T2D lies 5’ of BCL9 that, along with TCFL2, promotes beta-catenin’s transcriptional activity in the WNT signaling pathway. Additional hits occurred in genes affecting pancreatic (KCNJ6, KCNA1) and/or GABA (GABRR1, KCNA1) functions. Notable associations observed for genes previously identified at genome-wide significance in other populations included MC4R (Pgenotyped=4.49x10-4) for BMI and IGF2BP2 Pimputed_1000G=2.55x10-6) for T2D. Our results may provide novel functional leads in understanding disease pathogenesis in this Australian Aboriginal population.

  Study EGAS00001001004

• CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium Summary Results from Genomic Studies

  GWAS have successfully identified genetic loci associated with a variety of conditions such as type 2 diabetes and coronary disease. The large number of statistical tests required in GWAS has posed a special challenge because few studies that have DNA and high-quality phenotype data are sufficiently large to provide adequate statistical power for detecting small to modest effect sizes. Even before the era of GWAS, the requirement for large sample sizes and the importance of replication have served as powerful incentives for collaboration. Meta-analyses combining summary data from multiple sources have improved the ability to detect new loci. The Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium was formed to facilitate GWAS meta-analyses and replication among multiple large and well-phenotyped cohort studies. The design of the CHARGE Consortium was formed initially from 5 prospective cohort studies from the United States and Europe: the Age, Gene/Environment Susceptibility (AGES) - Reykjavik Study, the Atherosclerosis Risk in Communities (ARIC) Study, the Cardiovascular Health Study (CHS), the Framingham Heart Study (FHS), and the Rotterdam Study (RS). Additional studies have expanded the CHARGE consortium based upon the phenotypes and willingness to share information across the research community. In order to facilitate investigators across the world to examine relationships between phenotypes and genetic markers within CHARGE published reports, an open site is made available on dbGaP that provides the rsID and the p-value for inspection. Access to detailed summary statistics (including minor allele frequency, odds ratio/effect size) requires approval of a Data Access Request (DAR).

  Study phs000930

• Study on the Genetics of Alcoholism (COGA): Smoke Screen and Exome Sequencing

  This is a family study of alcoholism, in which the subjects have been drawn from the Collaborative Study on the Genetics of Alcoholism (COGA), a large, ongoing family-based study that includes subjects from seven sites around the US. COGA has gathered detailed, standardized data on study participants, including diagnostic and neurophysiological assessments. This project has already proved successful in identifying several genes that influence the risk for alcoholism and neurophysiological endophenotypes, which have been independently replicated. COGA data were included as part of two Genetic Analysis Workshops, and the phenotypes are familiar to the genetics community. Alcoholic probands were recruited from treatment facilities, assessed by personal interview, and after securing permission, other family members were also assessed. A set of comparison families was drawn from the same communities as the families recruited through an alcoholic proband. Assessment involved a detailed personal interview developed for this project, the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA), which gathers detailed information on alcoholism related symptoms along with other drugs and psychiatric symptoms. Many participants also came to the laboratories for electroencephalographic studies. Neurophysiological features that have been shown to be useful endophenotypes for which we have linkage and in some cases association results are included on a subset of the case-control sample: the beta power of the resting electroencephalogram (EEG), the P3(00) amplitude of the visual event-related potential (ERP), and the theta and delta event-related oscillations (EROs) underlying the P3.

  Study phs001208

• Cross-Sectional Characterization of Idiopathic Bronchiectasis

  This GDMCC protocol will study adult patients with non-CF, idiopathic bronchiectasis, whose genetic etiologies are not known. Idiopathic bronchiectasis is reportedly more common in females with certain tall, thin body types and associated with environmental organisms, such as nontuberculous mycobacterium (NTM). The other susceptibility factors predisposing to bronchiectasis or acquisition of NTM are unclear. The study will attempt to broaden the understanding of this disease by comparing gender-associated factors and NTM status. A relatively equal number of both females/males and NTM/non-NTM infected subjects will be enrolled. Approximately 300 people may be screened to find 260 eligible subjects, since a small number (e.g., 40 patients) may be diagnosed with PCD, vCF, or other known etiology as an explanation for the bronchiectasis. This single-visit protocol will use a systematic approach to characterize the physical features, radiographic patterns, and associated lower airway microbial flora. There is no natural history of disease course follow-up component to this protocol. Participants will have one outpatient clinic visit for evaluation with a physical examination including detailed body size measurements, medical history, collection of blood samples for routine lab tests and genetic analyses, and a chest X-ray if no recent one is available. Participants will also have tests of lung function, and measurement of a gas called nitric oxide in the nose. Participants whose initial tests show abnormal results may also be asked to have a nasal scrape to collect cell samples and/or a skin sweat test to measure salt concentrations. Participants will also have a sputum specimen collected during the visit and will be asked to collect two additional early morning sputum samples and a mouth rinse at home within 2 weeks of the clinic visit, and mail the sample collection materials to the research team. Careful evaluation and characterization of the physical and clinical characteristics will guide the genetic characterization of idiopathic bronchiectasis, and likely lead to an improved diagnostic approach. Identification of disease causing genes may provide new therapeutic targets.

  Study phs001279

• Collaborative Cohort of Cohorts for COVID-19 Research (C4R): Framingham Heart Study (FHS)

  Cohort DescriptionIn 1948, the researchers recruited 5,209 men and women between the ages of 30 and 62 from the town of Framingham, Massachusetts, and began the first round of extensive physical examinations and lifestyle interviews that they would later analyze for common patterns related to CVD development. Since 1948, the subjects have returned to the study every two years for an examination consisting of a detailed medical history, physical examination, and laboratory tests, and in 1971, the study enrolled a second-generation cohort -- 5,124 of the original participants' adult children and their spouses -- to participate in similar examinations. The second examination of the Offspring cohort occurred eight years after the first examination, and subsequent examinations have occurred approximately every four years thereafter. In 1994, the need to establish a new study reflecting a more diverse community of Framingham was recognized, and the first Omni cohort of the Framingham Heart Study, consisting of 506 participants, was enrolled. In April 2002 4095 third generation of participants, the grandchildren of the original cohort, were added. In 2003, 103 spouses of the offspring Cohort (NOS), and a second group of 410 Omni participants were enrolled. Through 2019, the original cohort has completed a total of 32 exams, the Offspring cohort 9 exams, the OMNI1 cohort 4 exams, and GEN3, NOS and OMNI2 cohorts each have completed 3 exams. The FHS is a joint project of the National Heart, Lung and Blood Institute and Boston University.Data Being Submitted Wave 1 questionnaire data includes 3967 variables for up to 3112 FHS participants in C4R.Wave 2 questionnaire data includes 448 variables for up to 2337 FHS participants in C4R.Dried Blood Spot/Serosurvey data includes 7 variables for up to 2189 FHS participants in C4R.Derived data includes 43 variables for up to 3151 FHS participants in C4R.Phenotype data includes 113 variables for up to 3151 FHS participants in C4R.

  Study phs002911

• Genome_Diversity_in_Africa_Project__Uganda

  Globally, human populations show structured genetic diversity as a result of geographical dispersion, selection and drift. Understanding this genetic variation can provide insights into the evolutionary processes that shape both human adaptation and variation in disease. Populations from SSA have the highest levels of genetic diversity. This characteristic, in addition to historical genetic admixture, can lead to complexities in the design of studies assessing the genetic determinants of disease and human variation. However, such studies of African populations are also likely to provide new opportunities to discover novel disease susceptibility loci and variants and refine gene–disease association signals. A systematic assessment of genetic diversity within SSA would facilitate genomic epidemiological studies in the region. The Genome Diversity in Africa Project (GDAP) aims to produce a comprehensive catalogue of human genetic variation in SSA, including single nucleotide polymorphisms (SNPs), structural variants, and haplotypes. This resource will make a substantial contribution to understanding patterns of genetic diversity within and among populations in SSA, as well as providing a global resource to help design, implement and interpret genomic studies in SSA populations and studies comprising globally diverse populations, complementing existing genomic resources. Specifically, we plan to carry out high depth whole genome sequencing of up to 2000 individuals across Africa (25 individuals from each ethnolinguistic group). Our scientific objectives are to: 1) develop a resource that provides a comprehensive catalogue of genetic variation in populations from SSA accessible to the global scientific community; 2) characterise population genetic diversity, structure, gene flow and admixture across SSA; 3) develop a cost-efficient, next-generation genotype array for diverse populations across SSA; and 4) facilitate whole genome-sequencing association studies of complex traits and diseases by developing a reference panel for imputation and resource for enhancing fine-mapping disease susceptibility loci. These scientific objectives will be supported by cross-cutting operational activities, including network and management of the consortium, research ethics, and research capacity building in statistical genetics and bioinformatics

  Study EGAS00001002523

• Providing safe access to sensitive human data across borders: Federated EGA becomes a reality

  Enabling discovery and access to sensitive data across national boundaries is vital for improving human health. It enables more powerful and efficient research by increasing the volume and diversity of data available for analysis. It allows us to better understand the causes of diseases – cancer, rare diseases, infectious diseases like COVID-19 – and develop new medicines and treatments. Sensitive human omics data are typically generated by research initiatives and shared using specialist repositories which provide services for data submission, discovery, and access. The EGA is one such repository. Established in 2008 at EMBL’s European Bioinformatics Institute (EMBL-EBI) in the UK, since 2012 the EGA (“Central EGA”) has been jointly managed by EMBL-EBI and the Centre for Genomic Regulation (CRG) in Spain. Many countries have emerging personalised medicine programmes which generate data from national initiatives. These programmes are driving a transition in human genomics from being research-driven to receiving funding through healthcare. Data generated in a clinical context are subject to stricter governance than research data and must follow national data protection legislation. To solve these challenges, the Federated EGA provides a network of connected resources to enable transnational discovery of and access to human omics data for research, while also respecting jurisdictional data protection regulations. In this way, the Federated EGA infrastructure supports the goals of European initiatives such as the 1+ Million Genomes initiative (1+MG), the European Health Data Space, and a number of EU-funded 1+MG implementation projects including Beyond 1 Million Genomes. The Federated EGA is made up of “Nodes” – typically nationally funded and operated – which store and manage data locally while allowing global discovery within the Federated EGA network. Since 2016, multiple parallel efforts, supported by ELIXIR and other transnational and national initiatives, have created technical and legal frameworks for establishing the Federated EGA. In 2022, the first five Nodes – Finland, Germany, Norway, Spain, and Sweden – officially joined the Federated EGA by signing Federated EGA Collaboration Agreements with Central EGA. The Finnish FEGA Node is operated by CSC - IT Center for Science and provides data management services according to national laws and the requirements of the EU General Data Protection Regulation (GDPR). These services provide tools and support for the whole life-cycle of sensitive research data from collating to analysis, publication, and authorised re-use. The development of the services has been a joint effort with the other Nordic nodes within NeIC's Tryggve and Heilsa projects, and funded by Finnish Ministry of Education and Culture and projects coordinated by ELIXIR Finland. Read more about Finnish FEGA signing. The German Human Genome-Phenome Archive (GHGA) strives to provide a national infrastructure as well as an ethical and legal framework that balances FAIR omics data usage and data protection needs for Germany. As a Germany-wide consortium funded by the German Research Foundation under the umbrella of the NFDI association, GHGA combines the expertise of 21 universities and research institutions to form a federated national infrastructure. Read more about GHGA signing. The German Human Genome-Phenome Archive (GHGA) strives to provide a national infrastructure as well as an ethical and legal framework that balances FAIR omics data usage and data protection needs for Germany. As a Germany-wide consortium funded by the German Research Foundation under the umbrella of the NFDI association, GHGA combines the expertise of 21 universities and research institutions to form a federated national infrastructure. Read more about GHGA signing. In Norway, a key component of the infrastructure is the services of The Sensitive Data Service (TSD) offered by USIT at University of Oslo. The Federated EGA Norway Node is developed by ELIXIR Norway and operated by the University of Oslo as the responsible legal entity. Core software modules are developed jointly with the other Nordic nodes in the NeIC Tryggve and Heilsa projects. Read more about FEGA Norway signing. The Spanish FEGA (es-FEGA) is a national service for storing sensitive biomedical data in Spain. Supported by the Spanish Institute of Bioinformatics (INB) in collaboration with Central EGA, sensitive research datasets are primarily hosted at the Barcelona Supercomputing Centre facilities. The Swedish Sensitive Data Archive is a secure data archive and sharing platform for sensitive datasets. It was developed by the National Bioinformatics Infrastructure Sweden (NBIS) in collaboration with other Nordic ELIXIR Nodes through the Tryggve and Heilsa projects funded by NeIC and coordinated with Central EGA through ELIXIR. Read more about the Swedish Node signing. The Swedish Sensitive Data Archive is a secure data archive and sharing platform for sensitive datasets. It was developed by the National Bioinformatics Infrastructure Sweden (NBIS) in collaboration with other Nordic ELIXIR Nodes through the Tryggve and Heilsa projects funded by NeIC and coordinated with Central EGA through ELIXIR. Read more about the Swedish Node signing. By providing a solution for secure and efficient management of human omics data, the Federated EGA aims to foster data reuse, enable reproducibility, accelerate biomedical research, and improve human health. Find out more Interested in setting up your own Federated EGA Node? Check out the FEGA Onboarding Knowledge Base for more information. The ELIXIR Federated Human Data Community is a great entry point for anyone interested in learning more about the Federated EGA. You can: Join the ELIXIR Federated Human Data Community mailing list (select “Human Data”) Attend the ELIXIR Federated Human Data Community calls

  Blog safe-access-to-sensitive-human-data-federated-ega

• Rapid Acceleration of Diagnostics - Digital Health Technologies (RADx-DHT): NIH Digital Health Solutions for COVID-19: Team SAE

  The goal of this project is to develop a smartphone-based platform to monitor and support individuals with COVID-19 symptoms (who may need testing) and those who have already tested positive. The app will integrate a Bluetooth-enabled thermometer and pulse oximeter into an approach uniquely designed for low-resource settings and underserved populations. This project will focus on the American Indian/Alaskan Native (AI/AN) underserved population and will determine the feasibility of the digital health solution to collect symptom survey data and vital data including temperature, pulse, and oxygen saturation level. The complete study will include 300 participants 100% medically underserved with at least 51% from the AI/AN community. A combination of hard and soft data will be collected consisting of vital data, medical history and questionnaire data, and participant COVID-19 viral and antibody testing results collected during the study.DOI: https://rapids.ll.mit.edu/10.57895/wv88-by98

  Study phs002534

• Functional Dynamics of the Elderly Gut Microbiome During Probiotic Consumption

  A mechanistic understanding of the health benefits conferred by consumption of probiotic bacteria has been limited by our knowledge of the resident gut microbiota and its interaction with the host. We used fecal samples from a study of twelve healthy individuals aged 65-80 to characterize the structure and functional dynamics of the gut microbiota associated with consumption of the single-organism probiotic, Lactobacillus rhamnosus GG ATCC 53103 (LGG). Samples were collected prior to probiotic consumption (day 0), on day 28 immediately after consuming 10^10 CFU of LGG twice daily for 28 days and day 56, one month after stopping LGG consumption. Our integrative approach incorporated bacterial 16S rRNA gene sequencing, whole-community expression profiling using RNA-seq, and metagenomic sequencing. We highlight the value of combinatorial 'omics methods and concomitant high-resolution informatics to probe the role that probiotics may play on the structure and function of the resident microbiota.

  Study phs000896

• MP2PRT: Genomic and Molecular Characterization of Biomarkers Associated with Tumor Angiogenesis, DNA Repair, and Immunologic Tolerance using Samples from the NRG Oncology Phase 3 Randomized Trial, GOG-0240 (NCT00803062)

  The Molecular Profiling to Predict Response to Treatment (MP2PRT) program is part of the NCI's Cancer Moonshot Initiative. The aim of this program is the retrospective characterization and analysis of biospecimens collected from completed NCI-sponsored trials of the National Clinical Trials Network and the NCI Community Oncology Research Program. This study is one of the selected studies under this program. For this study, genomic characterization (WGS, WXS, Total RNAseq, miRNAseq) has been performed on cervical tumor tissue from patients with advanced disease (persistent, recurrent, and metastatic) and matching germline samples. It is hypothesized that the characterization of these tissues using next generation sequencing will lead to the identification of relevant novel genetic aberrations within the immunologic, DNA repair, and tumor angiogenesis domains that dichotomize the study population into exceptional responders and non-responders to systemic therapy, with a spectrum of response manifesting between the two extremes.

  Study phs002293

• Exome sequencing of UK Birth Cohorts - Millennium Cohort Study

  Birth cohort studies involve repeated surveys of large numbers of individuals from birth and throughout their lives. They collect information useful for a wide range of life course research domains, and biological samples which can be used to derive data from an increasing collection of omic technologies. This rich source of longitudinal data, when combined with genomic data, offers the scientific community valuable insights from population genetics to rare disease associations. Avon Longitudinal Study of Parents and Children (ALSPAC)recruited 14,775 babies of predominantly White ethnicity in the Avon county of south-west England between 1991 and 1992. Born in Bradford (BiB) is similarly focused on a particular local area, the city of Bradford in the north of England, and recruited 13,858 babies between 2007 and 2011, of whom ~41% self-report as white British and ~59% as other ethnicities, predominantly Pakistani. Millennium Cohort Study (MCS) is a national cohort that recruited 18,827 children born between 2000 and 2002, intentionally over-sampling areas with high child poverty, large ethnic minority populations, and smaller UK nations (Wales, Scotland and Northern Ireland) Available here is a subset of exome-sequenced parents and children from these studies (CRAMS and post-QC VCFs) as detailed in https://doi.org/10.12688/wellcomeopenres.22697 [doi.org]. Phenotypic data is also available by submitting an application to the corresponding cohort: https://cls.ucl.ac.uk/cls-studies/millennium-cohort-study/ [cls.ucl.ac.uk]

  Dataset EGAD00001015372

• Exome sequencing of UK Birth Cohorts - Avon Longitudinal Study of Parents and Children

  Birth cohort studies involve repeated surveys of large numbers of individuals from birth and throughout their lives. They collect information useful for a wide range of life course research domains, and biological samples which can be used to derive data from an increasing collection of omic technologies. This rich source of longitudinal data, when combined with genomic data, offers the scientific community valuable insights from population genetics to rare disease associations. Avon Longitudinal Study of Parents and Children (ALSPAC)recruited 14,775 babies of predominantly White ethnicity in the Avon county of south-west England between 1991 and 1992. Born in Bradford (BiB) is similarly focused on a particular local area, the city of Bradford in the north of England, and recruited 13,858 babies between 2007 and 2011, of whom ~41% self-report as white British and ~59% as other ethnicities, predominantly Pakistani. Millennium Cohort Study (MCS) is a national cohort that recruited 18,827 children born between 2000 and 2002, intentionally over-sampling areas with high child poverty, large ethnic minority populations, and smaller UK nations (Wales, Scotland and Northern Ireland) Available here is a subset of exome-sequenced parents and children from these studies (CRAMS and post-QC VCFs) as detailed in https://doi.org/10.12688/wellcomeopenres.22697 [doi.org]. Phenotypic data is also available by submitting an application to the corresponding cohort: https://www.bristol.ac.uk/alspac/researchers/our-data/[bristol.ac.uk]

  Dataset EGAD00001015371

• H3Africa - Genomic and Environmental Risk Factors for Cardiometabolic Disease in Africans

  The long-term vision of the AWI-Gen Collaborative Centre (CC) is to build sustainable capacity in Africa for research that leads to an understanding of the interplay between genetic, epigenetic and environmental risk factors for obesity and related cardiometabolic diseases (CMD) in sub-Saharan Africa. The CC will be consolidated under the auspices of the University of the Witwatersrand (Wits) and the International Network for the Demographic Evaluation of Populations and Their Health in Developing Countries (INDEPTH). It will capitalize on the unique strengths of existing longitudinal cohorts, including the urban Soweto and rural Agincourt studies in South Africa (Wits based), and the well established INDEPTH demographic health and surveillance centers in Kenya, Ghana, Burkina Faso and South Africa. The centers offer established infrastructure, trained fieldworkers, long-standing community engagement, and detailed longitudinal phenotypic data, focusing on obesity and cardiometabolic health. Key strengths are harmonized phenotyping across sites, building on strong existing cohorts, and representation of the geographic and social variability of African populations. We aim to: 1. Build sustainable infrastructure (biobanks and laboratories) and capabilities (well characterized population cohorts, genotyping and bioinformatics) for genomic research on the African continent; 2. Understand the genomic architecture of sub-Saharan populations from west, east and south Africa to guide genomic studies (genome sequencing and high throughput SNP and CNV arrays using unrelated individuals and family trios to improve the accuracy of haplotype analyses) and; 3. Investigate the independent and synergistic genomic contributions to body fat distribution (BMI, hip/waist circumference, subcutaneous and visceral fat) in these populations considering the relevant environmental and social contexts (rural/urban communities, quickly transitioning obesity prevalence, differential HIV, TB, and malaria infection histories). We will investigate the effect of obesity and fat distribution on the risk for CMD in the longitudinal cohorts.

  Study EGAS00001002482

• European Genome-phenome Archive 15th Anniversary Celebration

  2023 marks the 15th Anniversary of the EGA, jointly managed by the European Bioinformatics Institute (EMBL-EBI) and the Centre for Genomic Regulation (CRG). To mark the occasion, a simultaneous celebration was held in both institutions on the 13th of December 2023. The teams gathered online to play a quiz game and celebrate all the achievements and milestones with two wonderful anniversary cakes. In 2008, the European Genome-phenome Archive was created at the EBI-EMBL in Cambridge to guarantee that human genome and phenome data were available to the international scientific community while data privacy was preserved. The six-person staff at the beginning of the project is now far behind us, with a team that reaches the number of 35 members. Since 2013, the European Bioinformatics Institute and the Centre for Genomic Regulation share responsibility for The European Genome-phenome Archive (EGA). At that time, the EGA had data for about 0,5 petabytes. Currently, the Archive contains more than 12 petabytes. 2023 comes to an end with several good news. The EGA has been renewed as an ELIXIR Core Data Resource. This was announced during the GA4GH 11th Plenary held in San Francisco last September when ELIXIR-Beacon was also confirmed to be a GA4GH Driver Project. Thus, the Beacon API has maintained this title since 2018. What’s more, the first Federated EGA dataset is now live on our website. This year we also launched new services for EGA users in September. By the numbers, in 2023 the EGA counts 2.5 PB archived, 371 studies published, 208 new submitters and 19 active projects in which the team is participating, among others. We look forward to continuing to support your research in 2024!

  Blog 15-anniversary

• NINDS-Genome-Wide Genotyping in Parkinson's Disease: First Stage Analysis and Public Release of Data

  Epidemiological studies have estimated a cumulative prevalence of PD of greater than 1 per thousand. When prevalence is limited to senior populations, this proportion increases nearly 10-fold. The estimated genetic risk ratio for PD is approximately 1.7 (70% increased risk for PD if a sibling has PD) for all ages, and increases over 7-fold for those under age 66 years. The role for genes contributing to the risk of PD is therefore significant. This study utilized the well characterized collection of North American Caucasians with Parkinson's disease, and neurologically normal controls from the sample population which are banked in the National Institute of Neurological Disorders and Stroke (NINDS Repository) collection for a first stage whole genome analysis. Genome-wide, single nucleotide polymorphism (SNP) genotyping of these publicly available samples was originally done in 267 Parkinson's disease patients and 270 controls, and this has been extended to include genome wide genotyping in 939 Parkinson's disease cases and 802 controls. The NINDS repository was established in 10-2001 towards the goal of developing standardized, broadly useful diagnostic and other clinical data and a collection of DNA and cell line samples to further advances in gene discovery of neurological disorders. All samples, phenotypic, and genotypic data are available to the research community including to academics and industry scientists. In addition, well characterized neurologically normal control subjects are a part of the collection. This collection formed the basis of this first stage study by Fung et al., and the expanded study by Simon-Sanchez et al. The genotyping data was generated and provided by the laboratory of Dr. Andrew Singleton NIA, and Dr. John Hardy NIA (NIH Intramural, funding from NIA and NINDS). Important links to apply for individual-level data Data Use Certification Requirements (DUC) Apply here for controlled access to individual level data Participant Protection Policy FAQ

  Study phs000089

• Center for Common Disease Genomics [CCDG] - Neuropsychiatric: Epilepsy: Epi25 Consortium

  Epilepsy genetics research is at an exciting stage where it is now feasible, with the power of a large cohort, to understand the more complex genetic components of epilepsy. The driving principle behind the Epi25 Consortium is collaboration and synergy - it is only possible to achieve this type of research by working together. The Epi25 Consortium was formed by the unification of various consortia, including Epi4K, EPIGEN, EuroEPINOMICS, the Epilepsy Phenome/Genome Project, EpiPGX, SANAD, and EpiCURE, and individual epilepsy investigators. The consortium's sample collection is the best resource in the world for this disease, both in terms of numbers of patients and quality of phenotypic information. As part of the NHGRI Centers for Common Disease Genomics (2016-2020), we aggregated a global sample collection from the various repositories for whole genome genotyping and whole exome sequencing (WES) at the Broad Institute (Cambridge, MA), initiating the largest and most ethnically diverse genetic study of epilepsy to date. The primary epilepsy phenotypes for Epi25 are based on strict standards agreed upon by the epilepsy community. The epilepsy cases contributed by Epi25 sites can be broadly defined as genetic generalized epilepsy (GGE), non-acquired focal epilepsy (NAFE), epileptic encephalopathies (EE), and lesional focal epilepsies. More information about eligibility criteria and phenotyping forms for Epi25, as well as the contributing centers, can be found here: epi-25.org The genomic data will be analyzed iteratively to identify genes and variants that explain these types of epilepsy. Summary clinical data compiled in the Epi25 clinical database will allow retrospective phenotypic analyses of groups of subjects with common genomic variant(s).

  Study phs001489

• Long-term Impact and Intervention with Micronutrients in Brazil, Parque Universitário, Community-Based Study

  The Parque Universitário Zinc-Vitamin A cohort was a prospective, double-blind, randomized placebo-controlled trial with 324 children enrolled between 2000 and 2004 and randomized into 8 treatment arms: Placebo, Vitamin A, Glutamine, Vitamin A + Glutamine, Zinc + Glutamine, Zinc, Vitamin A + Zinc, Vitamin A + Zinc + Glutamine.The Parque Universitário Zinc-Arginine study conducted between 2006 and 2010 enrolled 349 infants from the Parque Universitário favela in Fortaleza. Participants were randomized into Placebo, Zinc, and Zinc + Arginine arms.This submission includes genetic and corresponding anthropometric data on a subset of 210 participants from the Zinc-Vitamin A (96) and Zinc-Arginine cohorts (114). More information on this project and its related projects can be found here: Studies of diarrheal susceptibility, growth, and development, in pediatric populations in Northeastern Brazil

  Study phs003175

• Cancer Moonshot Biobank

  The National Cancer Institute initiated the Cancer Moonshot Biobank to accelerate research through the collection and distribution of biospecimens for key research efforts. The Biobank will engage with over one thousand cancer patients, being treated with standard-of-care therapies, for longitudinal biospecimen and data collection. Cancer patients will be enrolled into the study from a diverse participant population engaged at medical institutions throughout the U.S. The biospecimens will be distributed to qualified scientists to accelerate research progress. The Biobank program, working closely with Leidos Biomedical, Inc. (LBR), will partner with community hospitals and other medical institutions, designated as Biospecimen Source Sites (BSS), to engage and consent eligible participants and collect biospecimens and associated clinical data; work with a central Biospecimen Core Resource (BCR) to support biospecimen collection, processing and storage activities and perform pathology quality control; work with LBR's Molecular Characterization (MoCha) lab to perform clinical tumor molecular characterization assays and return results to patients and their physicians; and make the biospecimens and associated data available to researchers to accelerate cancer research progress. Return of clinical results, a dedicated Patient and Provider Engagement (PPE) website, electronic informed consent, local participant engagement projects, and an embedded ethical, legal and social issues sub-study will together support patient and provider engagement in the program. Cancer Moonshot Biobank imaging data is being made available in The Cancer Imaging Archive (TCIA) on a release schedule that is coordinated with the program releases of data to dbGaP. The imaging data can be found at the following link: Cancer Moonshot Biobank Imaging

  Study phs002192

• How mitochondrial DNA research can benefit from data reuse through EGA?

  Mitochondria are the only cellular organelles harbouring their own DNA, which encodes for proteins essentials in its respiration process. Despite its discovery in 1960, Mitochondrial DNA is often overlooked compared to nuclear DNA. Indeed, not all sequencing technologies capture a good representation of mtDNA (mitochondrial DNA). Recently, Ed Reznik's team (The Ed Reznik Lab | Memorial Sloan Kettering Cancer Center) carried out a massive analysis and reanalysis of single cells WGS (whole genome sequencing) produced with an amplification-free protocol (Direct library prep, DLP). As they demonstrated in the paper Single-cell mtDNA dynamics in tumors is driven by coregulation of nuclear and mitochondrial genomes - PMC, DLP is more effective in catching mtDNA compared to classical single-cell sequencing. These data allowed the team to unravel mtDNA dynamics in tumoral and normal samples, highlighting how mtDNA and nuclear DNA are co-regulated and their ratio is critical for phenotype. Data reuse to achieve the greatest results For this project, Reznik's team re-used data from 3 studies stored at the European Genome-phenome Archive (EGAS00001006343, EGAS00001004448 and EGAS00001003190) that comprised a total of 602 datasets. All of them were initially produced by the teams of Sam Aparicio and Sohrab P. Shah at the Memorial Sloan Kettering Cancer Centre, where Ed Reznik is a promising group leader. This demonstrates, once again, that networking, collaboration and data sharing can achieve the greatest results when coupled with innovative and smart ideas. At the EGA we are proud to provide the scientific community with an infrastructure to enable all those very smart ideas out there to find the right data to be tested.

  Blog mitochondrial-dna-research

• McGill Epigenomics Mapping Centre

  The McGill Epigenomics Mapping Centre (EMC) and Data Coordination Centre (EDCC) were established in 2012 at the McGill University and Genome Quebec Innovation Centre (Montreal, Canada) to support large-scale human epigenome mapping for a broad spectrum of cell types and diseases. Previous epigenetic studies have provided profiles of specific chromatin marks in relation to basic biological processes, and future studies of molecular mechanisms must build upon these proofs-of-concept by integrating sequence-based variation with multiple levels of epigenetic and transcriptional regulation across the genome of human tissues and animal disease models. This project leverages the high-throughput sequencing infrastructure and expertise in genomics and transcriptomics at the McGill Innovation Centre to carry out this research. Controlled access to the data by collaborators and the greater scientific community is gained via a portal, which takes advantage of Compute Canada high-performance computing cluster resources to manage the large volume of data associated from the generation of reference epigenome maps. McGill University is one of two Canadian mapping and data coordination centres, the other based at the Michael Smith Genome Sciences Centre in Vancouver, British Columbia. The generation of comprehensive epigenome maps at McGill University is part of a larger international effort that is coordinated by the International Human Epigenome Consortium (IHEC), whose overall long-term objective is to determine the extent to which the epigenome shapes human populations over generations and in response to the environment. This project is funded under the Canadian Epigenetics, Environment, and Health Research Consortium (CEEHRC) by the Canadian Institutes of Health Research and by Genome Quebec, with additional support from Genome Canada. The computing and networking infrastructure, and part of the software development, are provided by Compute Canada and CANARIE.

  Study EGAS00001000995

• MP2PRT: Comprehensive Genomic Profiling to Identify Alterations Associated with Relapse for NCI Standard Risk (SR) B-Lineage ALL and NCI High Risk (HR) B-Lineage ALL with Favorable Genetic Features

  The Molecular Profiling to Predict Response to Treatment (MP2PRT) program is part of the NCI's Cancer Moonshot Initiative. The aim of this program is the retrospective characterization and analysis of biospecimens collected from completed NCI-sponsored trials of the National Clinical Trials Network and the NCI Community Oncology Research Program. This study, titled "Comprehensive Genomic Profiling to Identify Alterations Associated with Relapse for NCI Standard Risk (SR) B-Lineage ALL and NCI High Risk (HR) B-Lineage ALL with Favorable Genetic Features," is one of the selected studies under this program. For this study, genomic characterization (WGS 30X, WXS, Total RNAseq) was performed on NCI Standard Risk B-lineage ALL patients who relapse and subsets of NCI High Risk B-lineage ALL patients who relapse as well as two non-relapse control cases for each relapse case. It was hypothesized that the comprehensive characterization of these sample sets will allow the identification of somatic genetic features that will facilitate early intervention to improve cure rates for those enrolled on future trials. Data were generated and genetic subtype was integrated with clinical variables, including age, presenting white blood cell count, sex, race, and levels of minimal residual disease at the end of induction. Additional secondary alterations were identified and included if they occurred in more than 10 patients. The study has been completed and a manuscript has been prepared.

  Study phs002005

• National Institute on Aging - Late Onset Alzheimer's Disease Family Study: Genome-Wide Association Study for Susceptibility Loci

  Alzheimer disease is the most common neurodegenerative disorder of the elderly affecting an estimated five million Americans. Genetic factors contribute to the risk for disease with heritability estimates ranging from 57% to 79%. More than a decade ago, the ε4 variant of APOE was identified and remains the most consistently replicated genetic variant influencing the risk of late onset Alzheimer disease. A segregation analysis suggests there may be four additional genes influencing the age-at-onset of Alzheimer disease. In 2007 there were 968 association studies in 398 candidate genes reported, but none replicated consistently. There are many reasons for the lack of consistency, but one important reason for the lack of progress is the paucity of a sufficient number of well characterized families and patients available to the entire scientific community. The extensive effort and expense required to ascertain such a population has been addressed by the NIA-LOAD Family Study. Its goal is to identify and recruit families with two or more siblings with the late-onset form of Alzheimer's disease and a cohort of unrelated, non-demented controls similar in age and ethnic background, and to make the samples, the clinical and genotyping data and preliminary analyses available to qualified investigators world-wide. Genotyping by the Center for Inherited Disease Research (CIDR) was performed using the Illumina Infinium II assay protocol with hybridization to Illumina Human 610Quadv1_B Beadchips. This genotyping represents the largest collection of families ever assembled with Alzheimer's disease combining the NIA-LOAD Genetics Initiative Multiplex Family Study, the National Cell Repository for Alzheimer's Disease (NCRAD) with additional controls from the University of Kentucky. These genotyping results will serve as a focal point for future research that will identify all of the remaining genetic variants in Alzheimer's disease.

  Study phs000168

• NHLBI GO-ESP: Early-Onset Myocardial Infarction (Broad EOMI)

  The NHLBI "Grand Opportunity" Exome Sequencing Project (GO-ESP), a signature project of the NHLBI Recovery Act investment, was designed to identify genetic variants in coding regions (exons) of the human genome (the "exome") that are associated with heart, lung and blood diseases. These and related diseases that are of high impact to public health and individuals from diverse racial and ethnic groups will be studied. These data may help researchers understand the causes of disease, contributing to better ways to prevent, diagnose, and treat diseases, as well as determine whether to tailor prevention and treatments to specific populations. This could lead to more effective treatments and reduce the likelihood of side effects. GO-ESP is comprised of five collaborative components: 3 cohort consortia - HeartGO, LungGO, and WHISP - and 2 sequencing centers - BroadGO and SeattleGO. In the Grand Opportunities Exome Sequencing Program Early MI Project (GO ESP - EOMI), we are sequencing cases with extremely early-onset MI drawn from 8 cohorts. These cohorts include five hospital or community-based studies that ascertained individuals based on MI status. These include PennCATH, Cleveland Clinic Genebank, Massachusetts General Hospital Premature Coronary Artery Disease Study (MGH-PCAD), Heart Attack Risk in Puget Sound (HARPS), and Translational Research Investigating Underlying Disparities in Myocardial Infarction Patients' Health Status (TRIUMPH). Cases were selected based on MI occurring in men aged ≤50 years and women aged ≤60 years. In addition, early-MI cases are being drawn from three population-cohort studies including the Framingham Heart Study, the Women's Health Initiative, and the Atherosclerosis Risk in Communities Study. MI-free controls are being drawn from five population-based cohort studies including the Framingham Heart Study, the Women's Health Initiative, Atherosclerosis Risk in Communities Study, Cardiovascular Health Study, and the Jackson Heart Study. Controls were selected based on two factors: (1) highest predicted risk for MI based on Framingham risk score; and (2) absence of prevalent or incident MI despite a high predicted risk.

  Study phs000279

• Data distribution Statistics

  EGA Statistics Bibliography Growth Community Archive Distribution Catalogue Here, we show the amount of data distributed by the EGA. Data Distributed / Live EGA Data Distribution / Live SFTP Aspera HTSGET lineChartLive("svg#ega-dist-live", document.querySelector("#ega-figure-dist-live figcaption")); Data Distributed The below figure represents the cumulative EGA data distribution via the download clients(v2 and v3.x api versions) using HTTPS, FTP, and download boxes using ASPERA. You can see cumulative values by clicking "Cumulative". EGA Data Distribution //lineChart('#ega-data-distribution svg.stats', 'https://stats.ega-archive.org/distribution', // ['Amount of Distributed Data', ['Aspera', 'Download Clients', 'Total']]) curveChart('#ega-data-distribution', [ { domId: 'stats-aspera', label: 'Aspera', url: 'https://stats.ega-archive.org/distribution/aspera' }, { domId: 'stats-sftp' , label: 'SFTP', url: 'https://stats.ega-archive.org/distribution/sftp' }, //{ domId: 'stats-htsget', label: 'HTSGET', url: 'https://stats.ega-archive.org/distribution/htsget' }, { domId: 'stats-streamer' , label: 'Download Client', url: 'https://stats.ega-archive.org/distribution/streamer' }, { domId: 'stats-total' , label: 'Total', url: 'https://stats.ega-archive.org/distribution/total' } ] );

  Documentation about/statistics/distribution

• Beacon v2 and Federated EGA, part of the GDI project Starter Kit to enable access to genomic and phenotypic data across borders

  The European Genomic Data Infrastructure project has released a ‘Starter Kit’ based on the rare disease and cancer proof-of-concepts from the Beyond 1 Million Genomes (B1MG) project. The Starter Kit, freely available to any interested parties, contains a set of software applications and components co-developed by the 20 GDI nodes and based on open community standards from the Global Alliance for Genomics and Health (GA4GH). Products in the Starter Kit give all countries the technical capability to access synthetic genomic and phenotypic data across borders. The image above shows the full workflow of the GDI Starter Kit user journey. The dotted circles are not included in the Starter Kit yet The EGA’s work is represented in the Starter Kit with Beacon v2 and Federated EGA among the software applications and components. About Beacon v2 Beacon is a protocol for data discovery. This API allows the search of genomic variants and associated information without breaching the datasets privacy. The European Genome-phenome Archive (EGA) is a key contributor to the Beacon v2 Protocol, the Beacon v2 Reference Implementation (B2RI) and the EGA Beacon(s). About Federated EGA The Federated EGA network offers a tool for data storage and sharing. Officially launched in 2022, this network of connected resources enables transnational discovery of and access to human omics data for research, while also respecting jurisdictional data protection regulations. The Federated EGA Onboarding Website contains all the information related to the establishment of a Federated Node.

  Blog beacon-v2-and-federated-ega-part-of-the-gdi-project-starter-kit

• Population Architecture using Genomics and Epidemiology (PAGE): Causal Variants Across the Life Course (CALiCo): Strong Heart Study (SHS) and Strong Heart Family Study (SHFS)

  The SHS is a study of cardiovascular disease and its risk factors among American Indian men and women. Using standardized methodology, it was designed to estimate cardiovascular disease mortality and morbidity and the prevalence of known and suspected cardiovascular disease risk factors and to assess the significance of these risk factors in a longitudinal analysis. The study included 13 American Indian tribes and communities in three geographic areas: an area near Phoenix, Arizona, the southwestern area of Oklahoma, and western and central North and South Dakota. The SHS included three components: The first was a survey to determine cardiovascular disease mortality rates from 1984 to 1994 among tribal members aged 35-74 years of age residing in the 3 study areas (the community mortality study). The second was the clinical examination of 4,500 tribal members aged 45-74. The SHS has completed three clinical examinations of the original Cohort (Phase I: 1989-1991; Phase II: 1993-1995; Phase III: 1998- 1999, respectively). The third component is the morbidity and mortality (M&M) surveillance of these 4,500 participants. Yearly SHS surveillance has only 0.2% loss to follow-up. All deaths and all nonfatal CVD events are classified by standardized criteria, including details of stroke and HF. The Strong Heart Family Study (SHFS) is a genetic epidemiological study designed to investigate the heritability of CVD and its risk factors and to localize genes that contribute to CVD risk in American Indians. SHFS participants include 3,838 family members that were >/=15 years old, and ascertained through sibships of the original SHS, from 94 extended (large, multigenerational) families. Exams have occurred in a pilot Phase III (1998-1999, 900 SHFS participants), in Phase IV (2001-2003), and Phase V (2006-2009). SHFS morbidity and mortality surveillance has occurred throughout the study phases, with 0.3% lost to follow-up. Genetic data includes complete pedigree information, DNA samples from all family members, a 10cM-spaced microsatellite map used for IBD estimation and to perform linkage analysis, genotypes for more than 12,000 SNPs in candidate regions, and genotypes from commercially available SNP assays.

  Study phs000580

• Genome_Diversity_in_Africa_Project___GemCode_libraries

  Globally, human populations show structured genetic diversity as a result of geographical dispersion, selection and drift. Understanding this genetic variation can provide insights into the evolutionary processes that shape both human adaptation and variation in disease. Populations from Africa have the highest levels of genetic diversity. This characteristic, in addition to historical genetic admixture, can lead to complexities in the design of studies assessing the genetic determinants of disease and human variation. However, such studies of African populations are also likely to provide new opportunities to discover novel disease susceptibility loci and variants and refine gene–disease association signals. A systematic assessment of genetic diversity within Africa would facilitate genomic epidemiological studies in the region.The Genome Diversity in Africa Project (GDAP) will extend and expand the African Genome Variation (AGV) project, an international collaboration aimed to produce a comprehensive catalogue of human genetic variation in Sub-Saharan Africa (SSA). Using a sequencing-based approach, GDA project aims to capture human genetic variation in Africa, including single nucleotide polymorphisms (SNPs), structural variants, and haplotypes. This resource will make a substantial contribution to understanding patterns of genetic diversity within and among populations in Africa, as well as providing a global resource to help design, implement and interpret genomic studies in African populations and studies comprising globally diverse populations, complementing existing genomic resources. Specifically, we plan to carry out whole genome sequencing at high depth (30x) of up to 1000 individuals across Africa (25 individuals from each ethnolinguistic group). We have already completed sequencing from 5 ethno-linguistic groups and we are now adding others.Our scientific objectives are to: 1) develop a resource that provides a comprehensive catalogue of genetic variation in populations from Africa accessible to the global scientific community; 2) characterise population genetic diversity, structure, gene flow and admixture across Africa; 3) develop a cost-efficient, next-generation genotype array for diverse populations across Africa; and 4) facilitate whole genome-sequencing association studies of complex traits and diseases by developing a reference panel for imputation and resource for enhancing fine-mapping disease susceptibility loci. These scientific objectives will be supported by cross-cutting operational activities, including network and management of the consortium, research ethics, and research capacity building in statistical genetics and bioinformatics.

  Study EGAS00001001589

• Genome_Diversity_in_Africa_Project__Benin

  Globally, human populations show structured genetic diversity as a result of geographical dispersion, selection and drift. Understanding this genetic variation can provide insights into the evolutionary processes that shape both human adaptation and variation in disease. Populations from SSA have the highest levels of genetic diversity. This characteristic, in addition to historical genetic admixture, can lead to complexities in the design of studies assessing the genetic determinants of disease and human variation. However, such studies of African populations are also likely to provide new opportunities to discover novel disease susceptibility loci and variants and refine gene–disease association signals. A systematic assessment of genetic diversity within SSA would facilitate genomic epidemiological studies in the region.The Genome Diversity in Africa Project (GDAP) aims to produce a comprehensive catalogue of human genetic variation in SSA, including single nucleotide polymorphisms (SNPs), structural variants, and haplotypes. This resource will make a substantial contribution to understanding patterns of genetic diversity within and among populations in SSA, as well as providing a global resource to help design, implement and interpret genomic studies in SSA populations and studies comprising globally diverse populations, complementing existing genomic resources. Specifically, we plan to carry out high depth whole genome sequencing of up to 2000 individuals across Africa (25 individuals from each ethnolinguistic group).Our scientific objectives are to: 1) develop a resource that provides a comprehensive catalogue of genetic variation in populations from SSA accessible to the global scientific community; 2) characterise population genetic diversity, structure, gene flow and admixture across SSA; 3) develop a cost-efficient, next-generation genotype array for diverse populations across SSA; and 4) facilitate whole genome-sequencing association studies of complex traits and diseases by developing a reference panel for imputation and resource for enhancing fine-mapping disease susceptibility loci. These scientific objectives will be supported by cross-cutting operational activities, including network and management of the consortium, research ethics, and research capacity building in statistical genetics and bioinformaticsThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/

  Study EGAS00001001688

• Genome Diversity in Africa Project: Uganda (2021-02-17)

  Globally, human populations show structured genetic diversity as a result of geographical dispersion, selection and drift. Understanding this genetic variation can provide insights into the evolutionary processes that shape both human adaptation and variation in disease. Populations from SSA have the highest levels of genetic diversity. This characteristic, in addition to historical genetic admixture, can lead to complexities in the design of studies assessing the genetic determinants of disease and human variation. However, such studies of African populations are also likely to provide new opportunities to discover novel disease susceptibility loci and variants and refine gene-disease association signals. A systematic assessment of genetic diversity within SSA would facilitate genomic epidemiological studies in the region. The Genome Diversity in Africa Project (GDAP) aims to produce a comprehensive catalogue of human genetic variation in SSA, including single nucleotide polymorphisms (SNPs), structural variants, and haplotypes. This resource will make a substantial contribution to understanding patterns of genetic diversity within and among populations in SSA, as well as providing a global resource to help design, implement and interpret genomic studies in SSA populations and studies comprising globally diverse populations, complementing existing genomic resources. Specifically, we plan to carry out high depth whole genome sequencing of up to 2000 individuals across Africa (25 individuals from each ethnolinguistic group). Our scientific objectives are to: 1) develop a resource that provides a comprehensive catalogue of genetic variation in populations from SSA accessible to the global scientific community; 2) characterise population genetic diversity, structure, gene flow and admixture across SSA; 3) develop a cost-efficient, next-generation genotype array for diverse populations across SSA; and 4) facilitate whole genome-sequencing association studies of complex traits and diseases by developing a reference panel for imputation and resource for enhancing fine-mapping disease susceptibility loci. These scientific objectives will be supported by cross-cutting operational activities, including network and management of the consortium, research ethics, and research capacity building in statistical genetics and bioinformatics . This dataset contains all the data available for this study on 2021-02-17.

  Dataset EGAD00001006976

• Exceptional Responders Initiative

  The Exceptional Responders Initiative is a pilot study to investigate the underlying molecular factors driving exceptional treatment responses of cancer patients to drug therapies. Study researchers will examine molecular profiles of tumors from patients either enrolled in a clinical trial for an investigational drug(s) and who achieved an exceptional response relative to other trial participants, or who achieved an exceptional response to a non-investigational chemotherapy. An exceptional response is defined as achievement of either a complete response or a partial response for at least 6 months duration in a trial or treatment where the overall response rate is < 10%. The hope is to discover underlying molecular features that can be further investigated and may eventually predict benefit from a given drug or class of drugs for a particular patient. This pilot project will successfully characterize approximately 100 cases of tumor tissue and, when available, case-matched germline DNA. All samples will undergo whole exome sequencing, and cases with sufficient nucleic acids will undergo additional analyses (e.g. whole genome sequencing, mRNA-sequencing, mi RNA sequencing, promoter methylation analysis, SNP etc). Each case will be annotated with demographic and clinical information, along with follow-up information minimally sufficient to correlate molecular profiles with response. Both retrospective and prospective collections will be considered. The project will also accept sequencing data and clinical data from patients who have had sequencing performed outside of this project. All data will be de-identified and placed in a controlled access database so other investigators may use them for additional insights. Clinically annotated tissue specimens meeting the criteria will be provided by groups participating in the Exceptional Cases Initiative to a Biospecimen Core Resource (BCR), which will perform quality control on the tissues, and will use a standard operating procedure to isolate nucleic acids. The nucleic acids will be shipped to a sequencing center to perform whole exome sequencing and analysis. These findings will be made available to the broader cancer research community in a controlled access database.

  Study phs001145

• Youth Drug Abuse, ADHD and Related Disorders

  There are two major aims with this study. 1. To describe the developmental trajectory of (a) a community-based sample of youth with a childhood diagnosis of ADHD that has been prospectively followed from childhood into adulthood (approximately a 17-year span), and (b) a clinical sample of youth that received drug abuse treatment during adolescence (variable time span). 2. To examine the association of phenotypes of drug involvement severity and risk alleles that prior research has suggested to be associated with drug abuse and externalizing disorders. The sample (N=607) consists of three groups based on youth status: Treatment, High Risk, and Control. These groups are defined as follows: Treatment - attended treatment or a brief intervention for a substance use disorder during adolescence (n=402); High Risk - elevated scores on standardized measures of disruptive behaviors during childhood based on teacher and parent reports (n=142); Control - normative scores during childhood on standardized measures of disruptive behaviors based on teacher and parent reports, and absent of any DSM-based behavioral/mental disorder when assessed during childhood based on parent report (n=66). Among the 610 participants who provided DNA, 607 are usable samples.

  Study phs001734

• 20 years after the first human genome release. Where are we heading?

  The genomic revolution equipped the scientists with millions of human genomes, entirely changing the way we envision, project and interpret science. Together with the amounts of data, it also evolved the need to respect the donors' right to privacy. Data protection laws flourished and, while they undeniably served to improve human rights and good practices in research, they added new layers of complication to the goal of data sharing. Nature Journal has dedicated a collection of remarkable articles to this 20th anniversary, where they portray how scientists did not fulfil the promise at the core of the HGP. The call for efficient sharing of human genomic data is nowadays more live than ever, with the animate issue regarding the faulty availability of data from COVID-19 patients, right when the pandemic is setting an unprecedented pressure on the scientific and medical community. Given its importance, this multi-faceted debate does not lack controversial opinions. Some researchers indeed consider that we should move toward more restrictive data access, giving more decisional power to the donors, despite that would inevitably diminish the usability and value of the data. Even if 20 years after we are still not there, at the EGA we are committed to make the dream behind the HGP a reality, working day by day to enable law-compliant data sharing.

  Blog 20-years-after-the-first-human-genome-release

• Youth-GEMs, the project using data to define the mental health trajectories of young people

  Mental health trajectories are shaped by genetic, cognitive, social, and environmental factors that are particularly influential during human development. How exactly the interplay between these factors is impacting mental health, however, is yet unknown. The project “Gene Environment interactions in Mental health trajectories of Youth (Youth-GEMs)”, funded by the European Commission under the Horizon Europe programme, aims to help reducing mental suffering among European youth. How do Youth-GEMs contribute to bettering mental health in young people? Youth-GEMs aims to identify specific neurological, (epi)genetic and environmental drivers on mental health trajectories of young people. To do so, the project is working on a public knowledge base on functional genomics of the developing human brain, between birth and 24 years old. Reliable predictive models for trajectories of onset and course of mental illness in young people of the general population in Europe will be developed. Additionally, a secure and FAIR data infrastructure in mental health is being produced. Engaging and empowering young people Youth-GEMs is also working on the engagement of young people in the scientific field of Psychiatry. For that, the project is developing initiatives such as Science Café, intended to create a learning community where ideas and stories are shared. The 10th Science Café will take place today, with the participation of Lauren Fromont from the EGA. How do the EGA contribute to Youth-GEMs? The contributions require careful data management and harmonisation: we are dealing with an extraordinary amount of data types, sources, and time points (since the studies are longitudinal). To analyse them together and to determine which factors and interactions are truly key to account for mental health trajectories, the variables need to be transformed in a common “language”, i.e., harmonised under a common data model. Further, to guarantee FAIRness of data storage and sharing for future projects that will further advance our knowledge in the mental health field, we are ensuring that data are processed securely but can also be discovered easily. Find out more information about the project in the Youth-GEMs website.

  Blog youth-gems-mental-health

• Coronary Artery Risk Development in Young Adults (CARDIA) Study - Gene Environment Association Studies Initiative (GENEVA)

  For the GENEVA CARDIA project, three genotype call sets were generated from a single set of array scans as a consequence of DNA sample quality problems. These call sets are designated "Birdsuite-1", "Birdsuite-2" and "Beaglecall". ("Beaglecall" used both Birdseed and BEAGLECALL calling algorithms.) An analysis-ready genotypic data set is provided in PLINK format for the "Beaglecall" set only, because it performs very well in QC analyses. Only raw CHP and ALLELE_SUMMARY files are provided for the two Birdsuite call sets because they have significant quality issues. Use of the Beaglecall set is highly recommended. Users of the other two call sets should proceed with caution. More details are given in the genotypic QC report. The CARDIA study, sponsored by the National Heart, Lung and Blood Institute (NHLBI), is a prospective, multi-center investigation of the natural history and etiology of cardiovascular disease in African-Americans and Whites 18-30 years of age at the time of initial examination. The initial examination included 5,115 participants selectively recruited to represent proportionate racial, gender, age, and education groups from 4 communities: Birmingham, AL; Chicago, IL; Minneapolis, MN; and Oakland, CA. Participants from the Birmingham, Chicago, and Minneapolis centers were recruited from the total community or from selected census tracts. Participants from the Oakland center were randomly recruited from the Kaiser-Permanente health plan membership. From the time of initiation of the study in 1985-1986, five follow-up examinations have been conducted at years 2, 5, 7, 10, 15, and 20. The Year 25 examination is scheduled to begin in 2010. This study is part of the Gene Environment Association Studies initiative (GENEVA, http://www.genevastudy.org) funded by the trans-NIH Genes, Environment, and Health Initiative (GEI). The overarching goal is to identify novel genetic factors associated with variation in longitudinal blood pressure profiles during the critical transition period from young adulthood to early middle-age; and to characterize their interactions with relevant environmental factors, such as body weight profiles. Genotyping was performed at the Broad Institute of MIT and Harvard, a GENEVA genotyping center. Data cleaning and harmonization were performed at the GEI-funded GENEVA Coordinating Center at the University of Washington.

  Study phs000309

• Genetic Testing to Understand and Address Renal Disease Disparities

  People of African ancestry (Blacks) have increased risk of kidney failure due to numerous socioeconomic, environmental, and clinical factors. Two variants in the APOL1 gene (GeneID: 8542) are now thought to account for much of the racial disparity associated with hypertensive kidney failure in Blacks. One in 7 AAs carry this risk allele, but it is nearly absent in other populations; the variants protect against infection with African trypanosomiasis which is endemic to Africa. However, this knowledge has not been translated into clinical care to help improve patient outcomes and address disparities. It is unknown whether patient or clinician knowledge of genetic risk impacts patient care (i.e., renal surveillance, BP medication use/intensification) or outcomes such as BP control and CKD. GUARDD is a randomized trial to evaluate the effects and challenges of incorporating genetic risk information into primary care. Hypertensive, nondiabetic, adults with self-reported African ancestry, without kidney dysfunction, are recruited from diverse clinical settings and randomized to undergo APOL1 genetic testing at baseline (intervention) or at one year (waitlist control). Prior to enrolling their patients, providers are educated about genomics and APOL1. Guided by a genetic counselor, trained staff return APOL1 results to patients and provide low-literacy educational materials. Real-time clinical decision support tools alert clinicians of their patients' APOL1 results and associated risk status at the point of care. Our academic - community clinical partnership designed a study to generate information about the impact of genetic risk information on our primary outcome - patient care (renal surveillance by clinicians, of serum creatinine and/or urine albumin tests. with a sub-aim of reduction of systolic blood pressure). Secondary outcomes include impact on primary outcomes at 12 months, psycho-behavioral differences of patients between groups and over time, clinician knowledge, attitudes and beliefs at baseline and 12 months, and differences in outcomes between those tested and not tested. GUARDD will help establish the effective implementation of APOL1 risk informed management of hypertensive patients at high risk of CKD, and will provide a robust framework for future endeavors to implement genomic medicine in diverse clinical practices. It will also add to the important dialog about factors that contribute to and may help eliminate racial disparities in kidney disease.

  Study phs001620

• dbGaP Collection: Compilation of Individual-Level Genomic Data for General Research Use

  This dbGaP Collection contains all authorized individual-level genomic datasets currently in dbGaP that are approved for General Research Use (GRU) and have no further limitations beyond those outlined in the model Data Use Certification Agreement. Access to this study will include any additional authorized individual-level GRU datasets that become available. Renewal of this study is required annually. Data Included in this Study Individual-level genomic data designated for general research use with no further use limitations or restrictions, that is, Data use does not require approval by an Institutional Review Board for secondary analyses Data have no publication embargo Data have no other use limitations (e.g., requirement for collaboration or publication; restricted for use by academic or not-for-profit organizations; restricted to health, medical, and/or biomedical research) In response to requests from the scientific community, the NIH implemented a change in the procedures for accessing individual-level GRU genomic data. Under the modified procedures, interested investigators can request GRU individual-level genomic datasets with a single application. However, please note that these data have not been harmonized. Additionally, to help expedite the processing of requests for individual-level GRU genomic datasets, the requests will be reviewed by a single, central Data Access Committee. The process for requesting these datasets is identical to the request process for non-GRU individual-level, controlled-access data, such as the expectation that investigators will abide by the NIH Policy for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies and Data Use Certification Agreement. Effective April 24, 2018, the Data Use Limitations (DUL) for the Genes and Blood Clotting Study (GABC) (phs000304) was updated to Health/Medical/Biomedical, Not-for-profit Use Only (HMB-NPU). Additionally, the submitting institutions have requested the removal of the National Heart, Lung, and Blood Institute (NHLBI) "Grand Opportunity" Exome Sequencing Project (GO-ESP) Lung Cohorts Exome Sequencing Project: Genetic modifiers of Pseudomonas aeruginosa (Pa) lung infection acquisition in cystic fibrosis (phs000254) from the dbGaP Compilation of Individual-Level Genomic Data for General Research Use (dbGaP Compilation) (phs000688). As such, data from studies phs000304 and phs000254 are no longer available as part of the dbGaP Compilation (phs000688). Investigators must submit separate Data Access Requests (DARs) for the two studies and be approved by the NHLBI Data Access Committee.

  Study phs000688