Search Results - EGA European Genome-Phenome Archive

Institut Curie Neuroblastoma Whole Genome Sequencing Diagnosis Relapse

Neuroblastoma, a clinically heterogeneous pediatric cancer, is characterized by distinct genomic profiles but few recurrent mutations. As neuroblastoma is expected to have high degree of genetic heterogeneity, study of neuroblastoma's clonal evolution with deep coverage whole-genome sequencing of diagnosis and relapse samples will lead to a better understanding of the molecular events associated with relapse. Samples were included in this study if sufficient DNA from constitutional, diagnosis and relapse tumors was available for WGS. Whole genome sequencing was performed on trios (constitutional, diagnose and relapse DNA) from eight patients using Illumina Hi-seq2500 leading to paired-ends (PE) 90x90 for 6 of them and 100x100 for two. Expected coverage for sample NB0175 100x100bp was 30X for tumor and constitutional samples. For the seven other patients expected coverage was 80X for tumor samples with PE 100x100, 100X in the other tumor samples and 50X for all constitutional samples (see table 1). Following alignment with BWA (Li et al., Oxford J, 2009 Jul) allowing up to 4% of mismatches, bam files were cleaned up according to the Genome Analysis Toolkit (GATK) recommendations (Van der Auwera et al., Current Protocols in Bioinformatics, 2013, picard-1.45, GenomeAnalysisTK-2.2-16). Variant calling was performed in parallel using 3 variant callers: GenomeAnalysisTK-2.2-16, Samtools-0.1.18 and MuTect-1.1.4 (McKenna et al., Genome Res, 2010; Li et al., Oxford J, 2009 Aug; Cibulskis et al., Nature, 2013). Annovar-v2012-10-23 with cosmic-v64 and dbsnp-v137 were used for the annotation and RefSeq for the structural annotation. For GATK and Samtools, single nucleotide variants (SNVs) with a quality under 30, a depth of coverage under 6 or with less than 2 reads supporting the variant were filter out. MuTect with parameters following GATK and Samtools thresholds have been used to filter our irrelevant variants. .SNVs within and around exons of coding genes overlapping splice sites.. Then,variants reported in more than 1% of the population in the 1000 genomes (1000gAprl_2012) or Exome Sequencing Project (ESP6500) have been discarded in order to filter polymorphisms. Finally, synonymous variants were filtered out. MuTect focuses on somatic by filtering with constitutional sample. Mpileup comparison between constitutional and somatic DNAs allowed us to focus also on tumor specific SNVs with GATK and Samtools. Finally, every SNV called by our pipeline and also supported in any constitutional samples were filtered our in order to prevent putative constitutional DNA coverage deficiency. Then we analyzed CNVs (copy number variants) with HMMcopy-v0.1.1 (Gavin et al., Genome Res, 2012) and control-FREEC-v6.7 (Boeva et al., Bioinformatics 2011) with a respective window of 2000bp and 1000 bp, and auto-correction of normal contamination of tumor samples for Control-FREEC. Finally we explored Structural variants (SVs) including deletions, inversions, tandem duplications and translocations using DELLY-v0.5.5 with standard parameters (Rausch et al., Oxford J, 2012). In tumors, at least 10 supporting reads were required to make a call and 5 supporting reads for the sample NB0175 with a coverage of only 40X (see table 2). To predict SVs in constitutional samples for subsequent somatic filtering, only 2 supporting reads were required in order not to miss one. To identify somatic events, all the SVs in each normal sample were first flanked by 500 bp in both directions and any SVs called in a tumor sample which was in the combined flanked regions of respective normal sample was removed (see graph 1). Deletions with more than 5 genes impacted or larger than 1Mb and inversions or tandem duplications covering more than 4 genes, were removed. We focused on exonic and splicing events for deletions, inversions, and tandem duplications. For translocation, we keep all SVs that occurred in intronic, exonic, 5'UTR, upstream or splicing regions. Bioinformatics detection of variations with Deep sequencing approach Once PE reads merged and adaptors trimmed by SeqPrep with default parameters, merged reads were aligned via the BWA (Li H. and Durbin R. 2009 PMID 19451168) allowing up to 1 differences in the 22-base-long seeds and reporting only unique alignments. Only reads having a mapping quality 20 or more have been further analysed. Variant calling software was not used, since we aimed to predict variations at low frequencies, observed in less than 1% of reads. Such variants require a custom approach. Using DepthOfCoverage functions of the Genome Analysis Toolkit (GATK) v2.13.2 (McKenna A, et al., 2010 Genome Research PMID: 20644199), we focused on high quality coverage of bases A, C, G and T at the targeted variant position. Depth of coverage of each base following a mapping quality higher than 20 and a base quality higher than 10 have been taken into account in order to focus only on high quality data. Aiming to determine the background level of variability at the studied regions, 10 control samples were included in the analysis. The same approach and filtering criteria have been applied as introduced above over the entire amplicons. In order to highlight variants, for each sample the frequencies of each bases at each amplicon position were then compared to those observed in the set of controls. Statistical analyses were performed with the R statistical software (http://www.R-project.org). Fisher’s exact two-sided tests with a Bonferroni correction were performed to compare percentages of bases between the data sets, i.e. for a given base between a case and the controls. Finally, significant variations were filtered-in once (i) a significant increase in the percentage of avariant base and (ii) a significant decrease in the percentage of it's reference base following our p.values criteria was observed (p.val < 0.05).

Dataset EGAD00001001356

dbGaP Collection: NHLBI Heart Failure Related dbGaP Data (No IRB requirement)

The National Heart, Lung, and Blood Institute (NHLBI) Big Data Analysis Challenge: Creating New Paradigms for Heart Failure Research has concluded. The NHLBI will continue to make this collection of data available to the research community.Past information regarding the Data Collection for the NHLBI Big Data Analysis Challenge: Creating New Paradigms for Heart Failure Research is below.The National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health (NIH), is inviting novel Solutions for the NHLBI Big Data Analysis Challenge: Creating New Paradigms for Heart Failure Research. The goal of the challenge is to foster innovation in computational analysis and machine learning approaches utilizing large-scale NHLBI-funded datasets to identify new paradigms in heart failure research. The challenge aims to address the need for new open source disease models that can define sub-categorizations of adult heart failure to serve as a springboard for new research hypotheses and tool development in areas of heart failure research from basic to clinical settings. NHLBI has a history of making considerable investments in the creation of deep data resources including: long-standing, deeply-phenotyped epidemiological cohorts, innovative clinical trials, and large-scale precision medicine efforts that have generated whole genome sequencing and "other omics" data for more than one-hundred thousand individuals. To provide challenge participants with streamlined access to data across NHLBI's numerous studies containing heart failure data, the NHLBI has created this dbGaP study collection. Data access for this collection is controlled by NHLBI's Data Access Committee. Challenge participants are required to follow the use restrictions and acknowledgement instructions from the original dataset(s). Please note that the data in this collection are not harmonized across studies or otherwise altered from the original study. The NHLBI Big Data Analysis Challenge: Heart Failure Data Collection contains all NHLBI studies currently in dbGaP that contain data that may be relevant to research on heart failure. The studies in this collection are approved for General Research Use (GRU), Health/Medical/Biomedical Use (HMB), or Disease-Specific Use (DS) that permits research on heart failure. These studies span a variety of study designs, inclusion and exclusion criteria, sample sizes, and provide a wide breadth and depth of phenotype data on study participants. The available genomic data in these studies also varies, including genotyping arrays, sequencing (targeted, exome, whole genome), and additional -omic data (e.g., RNA or metabolite profiles). Please refer to each study's individual accession page to learn more about how study data were collected. Challenge participants are reminded that in addition to dbGaP, NHLBI's Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC) contains other studies that have collected data relevant to heart failure and may wish to utilize BioLINCC data in the development of their Solution. Please refer to the individual accession page for each study in this collection to learn more about the history of each study.

Study phs001991

FHS-Net Social Networks

Note: Data Use Restrictions: The data must only be used for genetic research projects solely in the area of health-related social-network research. This study compiles detailed information on family and social ties linked to participants in the offspring cohort of the Framingham Heart Study. The investigators took computerized information from self-report data used by the FHS for over 30 years to facilitate health exam scheduling. These tracking sheets asked participants to identify people close to them, which were assumed by the investigators to indicate a social tie. Individuals are listed as "egos" (if the ties are from their perspective) and/or "alters" (if they are linked as a friend or family members to one of the other participants). All egos were FHS offspring participants while alters could be FHS participants in any cohort or non-participants. This information was combined with internal FHS pedigree data on family ties to list family member alters (as well as the nature of their relationship). The resultant dataset therefore includes each ego-alter tie, the nature of their relationship and the start and end dates for their ties for each of seven waves for the offspring study. Due to privacy concerns, all exam dates for individuals are listed relative to the initial FHS exam date. The study investigators chose a random, confidential date, to which all initial exam dates are linked (by number of months from random date to initial exam date). With this information, researchers can have access to the temporal relationships among participants' exam dates while remaining unaware of the actual exam dates for individual participants. During each clinic exam cycle, the participants undergo a detailed examination including physical examination, medical history, laboratory testing, and electrocardiogram. Over the years, other tests (that may not be performed at every exam cycle) have included pulmonary function, lifestyle, physical function, cognitive function questionnaires, and various noninvasive cardiovascular tests including echocardiograms. This study involves phenotypic data from these exams including (when available) basic body measurements (height, weight, blood pressure), laboratory values (blood sugar levels, LDL levels), information on smoking and alcohol use, and tests of depression and cognitive functioning. Important links to apply for individual-level data Data Use Certification Requirements (DUC) Instructions to Request Authorized Access Apply here for controlled access to individual level data Participant Protection Policy FAQ In 1948, researchers recruited men and women from the town of Framingham, Massachusetts, beginning the first round of extensive physical examinations and lifestyle interviews that would later be analyzed for common patterns related to CVD development. Initially, the Framingham Heart Study enrolled 5,209 men and women from the Framingham area who were between the ages of 28 and 62 years. Beginning in 1971, the Framingham Heart Study enrolled 5,124 men and women, who were either offspring of the original cohort or spouses of those offspring. In 2002, 4,095 third generation participants (men and women) were enrolled.

Study phs000153

The NCAA-DoD Concussion Assessment, Research, and Education (CARE) Consortium

Study Description: Established in 2014, the U.S. Department of Defense (DoD) and the National Collegiate Athletic Association (NCAA) funded the Concussion Assessment, Research and Education (CARE) Consortium to inform science, clinical care and public policy related to concussion and repetitive head impact exposure (HIE) in U.S. Military Service Academy (MSA) cadets and collegiate student-athletes. The primary aims of the initial study were to: (1) establish a multisite research consortium to characterize the effects of concussion and repetitive head impact exposure on brain health, (2) characterize the clinical sequelae and natural history of concussion, (3) characterize the effect of concussion and repetitive head impacts on brain structure and brain function. The 30 member institutions of the CARE Consortium (26 civilian universities/colleges and 4 military service academies) agreed to invite all varsity athletes to undergo multimodal clinical assessments at preseason baseline, and at 5 additional timepoints after concussion diagnosis. At the service academies, non-varsity athlete cadets/midshipmen were also studied. Assessment Categories At Each Time Point Baseline: • Demographics • Personal and Family History • Neurocognitive Assessment • Neurological Status • Postural Stability • Symptoms ACUTE POST-INJURY FOLLOW-UP (CARE 1.0) (24 hrs; 48hrs; Asymptomatic; Unrestricted Return to Play (RTP); 6 mos) • Neurocognitive Assessment • Neurological Status • Postural Stability • Symptoms CUMULATIVE & PERSISTENT EFFECTS. (CARE 2.0) In-Person Exit Visit; Post-grad Online • Demographics • Personal and Family History • Neurocognitive Assessment • Neurological Status • Postural Stability • Symptoms • PROs • MROs (at academies only) LONG-TERM EFFECTS (CARE/SALTOS Integrated (CSI))Annual Online Assessment (at MSAs only); In-Person Research Visits • Demographics • Symptoms • Psychological health • PROs • MROs (at academies only)A subset of athletes at 6 of the CARE institutions underwent additional assessments including multimodal MRI, proteomic and genomic biomarker characterization, and head impact quantification (helmet-based sensors). Assessment time points for the ARC/pARC Neurocognitive and Behavioral Testing was done at Baseline, <48hrs Post-Injury, Cleared for Return to Play Progression (Asymptomatic), Unrestricted Return to Play, 7 days following Return to Play, and at >60 days after final game of junior year until end of collegiate career.Blood biomarker collection was done at Baseline, <48hrs Post-Injury, Cleared for Return to Play Progression (Asymptomatic), 7 days following Return to Play, and at >60 days after final game of junior year until end of collegiate career. Multi-modal MRI studies were done at Baseline, <48hrs Post-Injury, Cleared for Return to Play Progression (Asymptomatic), 7 days following Return to Play, and at >60 days after final game of junior year until end of collegiate career. However, please note that only athletes from one study performance site completed a multi-modal MRI study at baseline.

Study phs002175

INCLUDE Data Hub: NDA GUIDs for Down Syndrome Research

The INCLUDE (INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE) Project is an NIH-wide collaboration that seeks to improve health and quality of life for people with Down syndrome. The INCLUDE Project Data Coordinating Center (DCC) and partners created the INCLUDE Data Hub, a centralized data resource that allows access to large-scale clinical and multi-omics datasets specific to Down syndrome and supports collaborative, cloud-based analysis to accelerate scientific discoveries related to Down syndrome and its co-occurring conditions. The INCLUDE Data Hub includes an innovative researcher data repository, a portal, and a cloud-based platform for data analysis. The portal provides access to de-identified demographics and clinical metadata, as well as multi-omics datasets, including whole genome sequences, transcriptomes, proteomes, and metabolomes. The INCLUDE Data Hub uses a 'registered access' model, whereby users can access the portal and associated data after agreeing to terms of use. From the Data Hub, users can also reach 'controlled access' data (e.g., whole genome sequences) only for those studies for which they have obtained approval by an NIH Data Access Committee through the corresponding dbGaP study. A thoughtful linkage strategy to identify duplicate participants across studies enables researchers to merge multiple datasets and data types to create richer datasets and reduce costly redundancies in large-scale data generation (e.g., -omics) while mitigating potential risks introduced by linkage.Based on recommendations from the NICHD Office of Data Science and Sharing, which completed a comprehensive assessment of existing Privacy Protecting Record Linkage (PPRL) and associated data governance solutions, the INCLUDE DCC and the associated NIH Steering Committee have implemented NIMH Data Archive Global Unique Identifiers (NDA GUIDs) in the INCLUDE Data Hub. The NDA GUID Tool is a government-owned and operated PPRL technology that enables researchers to link data from multiple sources to the same individual without revealing personally identifiable information (PII). With the NDA GUID Tool, the same participant information will return the same GUID whenever or wherever it is entered. The GUID itself is not personally identifiable information or protected health information. Sharing data with NDA GUIDs allows approved researchers to link together data on a single participant, even if the data were collected at different locations or through different studies or are distributed from different data repositories. This dbGaP study enables researchers to access an INCLUDE GUID Mapping File that includes all available NDA GUIDs and their associations to study-specific Participant IDs across studies in the INCLUDE Data Hub. This dbGaP study only distributes NDA GUIDs associated with the INCLUDE Data Hub datasets. To access the associated controlled-access datasets, add the corresponding dbGaP studies to your Data Access Request. A list of these studies is available on the INCLUDE Data Hub Portal: https://portal.includedcc.org/studies.

Study phs003678

Immunophenotyping in a COVID-19 Cohort (IMPACC) Transcriptomics and Genotyping Assays

IMPACC (IMmunoPhenotyping Assessment in a COVID-19 Cohort) is a prospective longitudinal cohort study (NCT04378777) launched in May 2020 in response to the worldwide pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It was funded by the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institute of Health (NIH). Patient enrollment and sample analysis involved 20 hospitals associated with 15 U.S. biomedical research centers and 11 centralized Core immunoassay laboratories.The study aimed to enable the identification of potential biomarkers and inform future therapeutic interventions using a longitudinal approach encompassing the whole disease course for a comprehensive understanding of the contributions of the pathogen and host immune response in modulating the manifestations, severity, and post-acute sequelae of the infection. IMPACC enrolled close to 1200 adult symptomatic, molecularly confirmed hospitalized COVID-19 patients in the study within 48 hours of their hospital admission. Clinical data and biological samples (blood, mid-turbinate nasal swabs, and esophageal aspirant) were collected according to minimal risk guidelines at enrollment and on days 4, 7, 14, 21, and 28. Biological samples were collected at 3-month intervals up to 12 months after hospital discharge to assess functional and immunologic recovery measures. Sample collection, processing, and storage procedures were standardized across sites, and samples were transported to centralized assay-specific core laboratories (Core Labs) in batches for testing and analysis. The description of outcome severity was not limited to survival versus death but encompassed a clinical trajectory approach using 5 groups leveraging longitudinal data based on time in the hospital, disease severity by ordinal scale based on the degree of respiratory illness, and presence or absence of limitations at discharge. Disease severity was assessed based on the degree of respiratory illness using a 7-point ordinal scale adapted from the World Health Organization COVID-19 and NIAID disease ordinal severity scales. DNA for genetic analyses was collected from whole blood at a single time point. To identify any genomic determinants of severe COVID-19 disease, single-nucleotide polymorphism (SNP) genotyping and exome sequencing were conducted to assess genetic variants associated with individual susceptibility to severe disease. In addition, IMPACC included bulk transcriptomic analysis of upper airway (nasal swaps) samples, lower airway (esophageal aspirant) samples, and peripheral blood mononuclear cells (PBMCs) to evaluate dynamic changes in cellular composition and cellular response during the course of the disease. Reads were aligned to the GRCh38 human reference genome. Additional information for the IMPACC study has been submitted to The Immunology Database and Analysis Portal (ImmPort) under study accession SDY1760. Further information and requests for resources and reagents should be directed to and will be fulfilled by the Lead Contact, Dr. Steven Kleinstein (steven.kleinstein@yale.edu).

Study phs002686

Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be Heart Health Study (nuMoM2b Heart Health Study)

Participants from study sites that recruited during the original study funded by NICHD of pregnant people, called nuMoM2b, participated in this study. The nuMoM2b-HHS1 was a prospective observational follow-up study of the nuMoM2b cohort consisting of interval contacts via phone or web every 6 months to about a year, and an in-person visit 2 to 7 years after the end of the nuMoM2b pregnancy including: Demographics Self-administered questionnaires Clinical measurements Lab results An in-home sleep breathing assessment for the subset of participants with at least one valid sleep breathing assessment during nuMoM2b Abstraction of medical records for pregnancies subsequent to nuMoM2b involving self-reported adverse pregnancy outcomes or multiple births Abstraction of medical records of selected cardiovascular risk-related events or procedures reported by participants. The study capitalized on the rich and unique data prospectively collected during nuMoM2b (biomarkers, uterine artery Doppler studies, fetal growth, psychosocial determinants, sleep, and blood pressure) and rigorous definitions of adverse pregnancy outcomes. These data are stored in the NICHD repository DASH (https://dash.nichd.nih.gov/study/226675). A total of 8,838 nuMoM2b participants were targeted for contact during nuMoM2b-HHS and 7,872 participants were reached, of whom 7,003 completed one or more interval contacts. Of these, 5,206 agreed to the visit, and 4,508 attended an in-person visit.

Study phs002808

NHLBI and NIA The New England Centenarian Study (NECS)

Supercentenarians (age 110+ years old) generally delay or escape age-related diseases and disability well beyond the age one hundred and this exceptional survival is likely to be influenced by a genetic predisposition that includes both common and rare genetic variants. In this report, we describe the complete genomic sequences of male and female supercentenarians, both age >114 years old. We show that: (1) the sequence variant spectrum of these two individuals' DNA sequences is largely comparable to existing non-supercentenarian genomes; (2) the two individuals do not appear to carry most of the well-established human longevity enabling variants already reported in the literature; (3) they have a comparable number of known disease-associated variants relative to most human genomes sequenced to date; (4) approximately 1% of the variants these individuals possess are novel and may point to new genes involved in exceptional longevity; and (5) both individuals are enriched for longevity-associated variants that we discovered through a large genome-wide association study. These analyses suggest that there are both common and rare longevity associated variants that may counter the effects of disease predisposing variants and extend lifespan. The continued analysis of the genomes of these rare individuals who have survived to extremely old ages should provide insight into the processes that contribute to the maintenance of health during extreme ageing.

Study phs000451

NIMH Human Middle Temporal Gyrus (MTG) Cell Types

Elucidating the cellular architecture of the human neocortex is central to understanding our cognitive abilities and susceptibility to disease. In this study, we applied single nucleus RNA sequencing to perform a comprehensive analysis of cell types in the middle temporal gyrus of human cerebral cortex. We identify a highly diverse set of excitatory and inhibitory neuronal types, many of which are relatively sparse. Additionally, we found that excitatory types are less layer-restricted than expected based prior knowledge from cell morphologies and from mouse studies. Comparison to a similar mouse cortex single cell RNA-sequencing dataset revealed a surprisingly well-conserved cellular architecture that enables matching of homologous types and predictions of human cell type properties. Despite this general conservation, we also find extensive differences between homologous cell types in human and mouse, including dramatic alterations in proportions, laminar distributions, gene expression, and morphology. These species-specific features emphasize the importance of directly studying human brain. This study conducted by the Allen Institute for Brain Science was supported by the Allen Institute for Brain Science and by US National Institutes of Health grant U01 MH114812-02 to E.S.L. Collaborators request that publications resulting from these data cite their original publication: Hodge RD, Bakken TE, et al. Conserved cell types with divergent features between human and mouse cortex. bioRxiv. 2018 doi: 10.1101/384826.

Study phs001790

Population Genetic Testing and SERPINA1 Sequencing Identifies Unidentified Alpha-1 Antitrypsin Deficiency Alleles and Gene-Environment Interaction with Hepatitis C Infection

Design and aims: Data were available through an institutional effort to combine de-identified electronic health records (EHR) data with genomic information from a DNA biobank. The design of this work was a retrospective cohort study in which we investigated the rates of liver transplantation and hepatitis C infection as it relates to genotype risk for alpha-1 antitrypsin deficiency (AATD). We used regression analysis to look for relationships between these risks and outcomes. This led to further investigation of environmental exposures and phenotypes as it related to the underlying genotypic risk. Population information: The cohort consisted of 72,027 individuals of European ancestry for whom genotype and EHR data were available. Molecular technologies employed: Genome-wide genotyping was previously performed using the Illumina Infinium Expanded Multi-Ethnic Genotyping Array plus custom content (referred to as the Vanderbilt University Medical Center BioVU MEGAEX). Individuals' AATD-related alleles were inferred from the genotyping data. Principal findings of the study: Liver transplantation was associated with presence of the Z AATD allele and with hepatitis C infection. There was a significant interaction between AATD genotype groups and hepatitis C infection as it related to liver transplantation. Data available through dbGaP: Inferred AATD genotype status, sex, age, length of EHR in years, presence/absence of AATD clinical diagnosis, liver transplant status, and hepatitis C infection status.

Study phs003297

GWAS in African Americans, Latinos and Japanese

The Multiethnic Cohort Study is a population-based prospective cohort study (n=215,251) that was initiated between 1993 and 1996 and includes subjects from various ethnic groups - African Americans and Latinos primarily from Californian (great Los Angeles area) and Native Hawaiians, Japanese-Americans, and European Americans primarily from Hawaii. State drivers' license files were the primary sources used to identify study subjects in Hawaii and California. Additionally, in Hawaii, state voter's registration files were used, and, in California, Health Care Financing Administration (HCFA) files were used to identify additional African American study subjects. In the cohort, incident cancer cases are identified annually through cohort linkage to population-based cancer Surveillance, Epidemiology, and End Results (SEER) registries in Hawaii and Los Angeles County as well as to the California State cancer registry. Information on estrogen receptor status is also obtained through these registries. Blood sample collection in the MEC began in 1994 and targeted incident breast cancer cases and a random sample of study participants to serve as controls for genetic analyses. Subjects are frequency matched on age at blood draw and ethnicity. The following number of breast cancer cases and controls were genome-wide scanned as part of this study: African Americans, 473 cases and 464 controls; Japanese: 885 cases and 822 controls; Latinos, 520 cases and 544 controls.

Study phs000517

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

Genetic Determinants of Viral Clearance in HCV-Infected Populations

The World Health Organization estimates there are 170 million persons with HCV infection worldwide, and an estimated 4 million persons are infected in the United States. Persistent HCV infection can cause cirrhosis and hepatocellular cancer. Long term disease consequences do not occur in persons who spontaneously recover. It is not known why 10-40% recover from hepatitis C (and are not at increased risk of cirrhosis and cancer), but that knowledge would contribute to efforts to treat and/or prevent HCV infection. The overall purpose of this study is to investigate the host genetic basis for recovery from hepatitis C virus (HCV) infection. There is strong evidence that host genetic differences determine HCV recovery. After accidental exposure to the same HCV inoculum, some persons recover while others develop persistent infection. Recovery from HCV infection is an outstanding phenotype for genetic studies since both viral exposure and viral recovery can be ascertained with high sensitivity and specificity and since there are no known viral or environmental determinants. The study group is comprised of an ethnically and geographically diverse international population. All cohorts comprising this study group of 3350 individuals are well characterized. This case-control study is comprised of approximately 40% clearance individuals who are matched by age and HIV status within their respective cohorts at a ratio of 1:1 or 1:2 with HCV chronically infected individuals.

Study phs000248

NHLBI GO-ESP: Family Studies (JHMI-Molecular Genetics of Atypical Cystic Fibrosis (CF) Study)

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. Cystic fibrosis (CF) patients without detectable disease-causing mutations in CFTR present a clinical phenotype very similar to, but possibly discrete from, classic CF. We hypothesize that the phenotype of these atypical CF patients is not due only to mutations in the carbonic anhydrase gene CA12 or in the genes encoding the epithelium sodium ion channel ENaC, but is due to mutations in novel genes that have yet to be associated with CF. The goal of this study is to determine the molecular etiology of this atypical CF.

Study phs000556

The Human Gut Microbiome and Recurrent Abdominal Pain in Children

This project explores the nature of the human intestinal microbiome in healthy children and children with recurrent abdominal pain. The overall goal is to obtain a robust knowledge-base of the intestinal microbiome in children without evidence of pain or gastrointestinal disease, children with functional abdominal pain, and children with abdominal pain and changes in bowel habits (irritable bowel syndrome). Multiple strategies have been deployed to navigate and understand the nature of the intestinal microbiome in childhood. These strategies include 454 pyrosequencing-based strategies to sequence 16S rRNA genes and understand the detailed composition of microbes in healthy and disease groups. Microarray-based hybridization with the PhyloChip and quantitative real-time PCR (qPCR) probes are being applied as complementary strategies to gain an understanding of the intestinal microbiome from various perspectives. Data collected and analyzed during the HMP UH2 and UH3 Demo project, from a set of healthy and IBS children may enable the identification of core microbiomes in children in addition to variable components that may distinguish healthy from diseased pediatric states. We are currently analyzing the dataset for the presence of disease-specific signatures in the human microbiome, and correlating these microbial signatures with pediatric health or IBS disease status. This study explores the nature of core and variable human microbiomes in pre-adolescent healthy children and children with recurrent abdominal pain.

Study phs000265

Characterizing the Neurobehavioral Phenotype(s) in MPS III (Pilot Study)

Mucopolysaccharidosis III (MPSIII) syndrome is characterized by a severe cognitive decline ending in dementia and death. MPSIII is also associated with a range of abnormal and disruptive behaviors that can include, but go well beyond, childhood noncompliance and oppositionality. The purpose of this study is to conduct a cross-sectional investigation to identify the behavioral phenotype and its neural basis in MPSIII. An overall goal of this research is to develop easily administered, sensitive and specific neurobehavioral markers to characterize the behavioral phenotype(s) of MPSIII, track their progression, and to delineate their possible neural substrates. The study looks to develop develop a sensitive and specific behavioral rating of disease progression in MPS III which can be used for clinical outcome studies. The research objectives are: Develop a measure for the use of health professionals to use in tracking MPSIII phenotypes and disease progression. Test our model of MPSIII with objectively recorded behaviors in a well-defined experimental setting. Elucidate the neural bases of MPSIII by correlating behavioral profiles with changes in brain structures through quantitative neuroimaging. Determine the relationship between the loss of cognitive functions and development of behavioral abnormalities in MPSIII. This is an observational pilot study that will enroll 45 individuals with MPS III Type A or B. Those participating in the study will be evaluated during a one-day assessment and chart review.

Study phs001330

NHLBI TOPMed: Genome-Wide Association Study of Adiposity in Samoans

The individuals sequenced here represent a small subset of the parent study (described below) and were carefully selected for the purpose of creating a Samoan-specific reference panel for imputation back into the parent study. The INFOSTIP algorithm of Gusev et. al. (2012) (PMID: 22135348) was used to optimally choose the individuals for sequencing. The research goal of the parent study (dbGaP ID phs000914) is to identify genetic variation that increases susceptibility to obesity and cardiometabolic phenotypes among adult Samoans using genome-wide association (GWAS) methods. DNA from peripheral blood and phenotypic information were collected from 3,119 adult Samoans, 23 to 70 years of age. The participants reside throughout the independent nation of Samoa, which is experiencing economic development and the nutrition transition. Genotyping was performed with the Affymetrix Genome-Wide Human SNP 6.0 Array using a panel of approximately 900,000 SNPs. Anthropometric, fasting blood biomarkers and detailed dietary, physical activity, health and socio-demographic variables were collected. We are replicating the GWAS findings in an independent sample of 2,500 Samoans from earlier studies. After replication of genomic regions and informative SNPs in those regions, we will determine sequences of the important genes, and determine the specific genetic variants in the sequenced genes that are associated with adiposity and related cardiometabolic conditions. We will also identify gene by environment interactions, focusing on dietary intake patterns and nutrients.

Study phs000972

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

INSIGHT (Intervention Nurses Start Infants Growing on Healthy Trajectories) Cohort

This is a study of the biological risk factors for children enrolled in the INSIGHT (Intervention Nurses Start Infants Growing on Healthy Trajectories) study. INSIGHT is a randomized, controlled trial testing a responsive parenting intervention designed for the primary prevention of childhood obesity against a safety control. These first-born children were deeply studied in this time period with data collected on a wide variety of variables including mode of delivery, gender, weight and height (collected at 7 time points), medication usage, diet information, and maternal health information (gestational weight gain, gestational diabetes, smoking during pregnancy). This study includes a survey of the oral and gut microbiota from 226 mother-child dyads. It was designed to investigate the relationship between a cross-sectional view of the child's microbiome (at two years of age) and the patterns of growth between birth and 2 years. Microbiome samples from children (buccal swab and stool sample) and their mothers (buccal swab) are collected at the children's 2-year clinical research visit. Stool metabolites have also been assayed for a subset of the 226 children using 1H-NMR. Additionally, we genotyped the same individuals for SNPs across the genome. For a subset of 48 individuals we have added second-born siblings. For these additional 48 children, we characterized the methylation pattern across the genome using cord blood and placenta samples.

Study phs001498

The Bangladesh Environmental Enteric Dysfunction (BEED) Study

Environmental enteric dysfunction (EED), a sub-acute inflammatory condition of the small intestinal mucosa of unclear etiology, has been associated with a variety of environmental exposures and host factors and is implicated in growth faltering. Linear growth faltering usually occurs within the first two years of life and in most of the cases is irreversible demanding early diagnosis for treatment to be successful. The objectives of 'The Bangladesh Environmental Enteric Dysfunction Study (BEED)' are to investigate role of EED in malnutrition, examine the biology of EED to identify common biological pathways for potential interventions, to validate a system for histological scoring for EED and test the effectiveness of nutritional interventions in improving the growth parameters in children with stunting and or EED. In Bangladesh, participants are recruited from two age groups; a child cohort and a malnourished an adult cohort. In addition, two control groups are recruited for comparison consisting of a) children that are undergoing endoscopy as a part of their clinical care at the University of Virginia Health system (UVAHS) and b) an adult well-nourished control group recruited from the Gastroenterology Outpatient Department of Dhaka Medical College and Hospital in Bangladesh. The description of the study design and procedures of the study can be obtained from Mahfuz M, Das S, Mazumder RN, et al., 2017, PMID: 28801442.

Study phs001891

Investigating Host Genetic Risk Factors for Tuberculosis in Highly Endemic South African Populations

It is apparent from our recent population genetic and admixture mapping work 1–3 that a substantial part of the ancestral input into the South African Coloured (SAC) population is from the San or Khoe groups, which are not well represented in publicly available genetic databases. It is a reasonable assumption that the SAC population in the Western Cape may have derived more genetic input from the present KhoeSan population in the Northern Cape than the San residing in Namibia. It was concluded by our group that it is indeed the southern African KhoeSan group, the ≠Khomani, that best represent the KhoeSan contribution seen in the SAC 4. More recently, it has been shown that there are ancestry related increases in TB susceptibility, especially with increased Bantu-speaking African and KhoeSan ancestry 5. We aim to elucidate the epidemiological and human-host genetic risk factors for TB and the immunological pathways modulating TB infection. The proposed sub-study will enroll people evaluated for TB at Northern Cape community health clinics and their contacts from their households and/or community. We will conduct a demographic interview, collect saliva, which will be used for genetic analysis, and blood to determine latent TB infection status and capture immunological responses to mycobacterial infections at the cellular level and RNA sequencing.

Study EGAS00001007850

Finnish_population_cohort_genotyping_B

The FINRISK cohorts comprise the respondents of representative, cross-sectional populationsurveys that are carried out every 5 years since 1972, to assess the risk factors of chronicdiseases (e.g. CVD, diabetes, obesity, cancer) and health behavior in the working agepopulation, in 3-5 large study areas of Finland. DNA samples were collected in the followingsurvey years: 1987, 1992, 1997, 2002, 2007, and 2012. The MONICA and EHES (EU)procedures were applied in phenotype collection (cf. MORGAM) and a wide spectrum oflaboratory tests was carried out from serum and plasma samples. Background information onsocioeconomic status, medical history, diet, exercise, measured anthropometric measures,etc. was collected by questionnaires and during a clinical visit. Plasma/serum samples arestill available for the 2002-2012 cohorts. The cohort sizes are 6000-8800 per survey. Thecohorts have been followed up by linking them to the national hospital discharge register,causes-of-death register and cancer register.This project is an extension to previous efforts to build a catalogue of Finnish genome widedata on population-based Finsrisk samples with rich phenotypic characterisations and healthregistry link-up. These samples will extend the current Sequencing Initiative Suomi (SISu)samples with a combination of genotyping using Illumina HumanCoreExome array and SISu-based imputation. This will lead to high confidence common and low frequency variantcatalogue. The project will be funded by Aarno Palotie’s remaining faculty fundscomplemented by Finnish funding from FIMM.

Study EGAS00001001047

Mutational signatures of aflatoxin

Aflatoxin B1 (AFB1) is a mutagen and IARC (International Agency for Research on Cancer) Group 1 carcinogen that causes hepatocellular carcinoma (HCC). Here we present the first whole genome data on the mutational signatures of AFB1 exposure from a total of > 40,000 mutations in four experimental systems: two different human cell lines, and in liver tumors in wild-type mice and in mice that carried a hepatitis B surface antigen transgene – this to model the multiplicative effects of aflatoxin exposure and hepatitis B in causing HCC. AFB1 mutational signatures from all four experimental systems were remarkably similar. We integrated the experimental mutational signatures with data from newly-sequenced HCCs from Qidong County, China, a region of well-studied aflatoxin exposure. This indicated that COSMIC mutational signature 24, previously hypothesized to stem from aflatoxin exposure, indeed likely represents AFB1 exposure, possibly combined with other exposures. Among published somatic mutation data, we found evidence of AFB1 exposure in 0.7% of HCCs treated in North America, 1% of HCCs from Japan, but 16% of HCCs from Hong Kong. Thus, aflatoxin exposure apparently remains a substantial public health issue in some areas. This aspect of our study exemplifies the promise of future widespread resequencing of tumor genomes in providing new insights into the contribution of mutagenic exposures to cancer incidence.

Study EGAS00001002490

Genomic insights into the pathogenesis of Epstein-Barr virus-associated diffuse large B-cell lymphoma by whole-genome and targeted amplicon-based sequencing

Epstein–Barr virus (EBV)-associated diffuse large B-cell lymphoma not otherwise specified (DLBCL NOS) constitutes a distinct clinicopathological entity in the current World Health Organization (WHO) classification, yet its genomic features remain sparsely characterized. Combining whole-genome sequencing (WGS), targeted amplicon sequencing (tNGS) and fluorescence in-situ hybridization (FISH) of tumours from 47 cases of EBV+ DLBCL we delineate the genomic landscape of this rare disease. Interrogating WGS data by sequential gene-set enrichment and network-diffusion we describe an accumulation of mutations affecting the nuclear factor κB (NFκB) pathway (CSNK2A2, CARD10), IL-6/JAK/STAT (SOCS1/3, STAT3) and WNT signalling (FRAT1, SFRP5) alongside aberrations in immunological processes like interferon-response. Further, WGS uncovered structural aberrations including 6q deletions (5/8 patients), which were subsequently validated by FISH (14/32 cases). Integrated WGS and tNGS analysis emphasized a profile distinct from EBV-negative DLBCL enriched for mutations in ARID1A (45%), KMT2A/D (32/30%), ANKRD11 (32%), NOTCH2 (32%). Expanding on previous reports, we identified recurrent alterations in CCR6 (15%), DAPK1 (15%), TNFRSF21 (13%), CCR7 (11%) and YY1 (6%). Our comprehensive description of the mutational landscape in EBV+ DLBCL substantiates the evidence of its pathobiological independence. Further, these observations aid in the refinement of the molecular taxonomy for aggressive lymphomas and guides future therapeutic strategies.

Study EGAS00001004941

Genetic insights into the biological mechanisms governing human ovarian ageing

Reproductive longevity is critical for fertility and impacts healthy ageing in women, yet insights into the underlying biological mechanisms and treatments to preserve it are limited. Here, we identify 290 genetic determinants of ovarian ageing, assessed using normal variation in age at natural menopause (ANM) in ~200,000 women of European ancestry. These common alleles influence clinical extremes of ANM; women in the top 1% of genetic susceptibility have an equivalent risk of premature ovarian insufficiency to those carrying monogenic FMR1 premutations. Identified loci implicate a broad range of DNA damage response (DDR) processes and include loss-of-function variants in key DDR genes. Integration with experimental models demonstrates that these DDR processes act across the life-course to shape the ovarian reserve and its rate of depletion. Furthermore, we demonstrate that experimental manipulation of DDR pathways highlighted by human genetics increase fertility and extend reproductive life in mice. Causal inference analyses using the identified genetic variants indicates that extending reproductive life in women improves bone health and reduces risk of type 2 diabetes, but increases risks of hormone-sensitive cancers. These findings provide insight into the mechanisms governing ovarian ageing, when they act across the life-course, and how they might be targeted by therapeutic approaches to extend fertility and prevent disease.

Study EGAS00001004947

1169 results for "NHMRC+youth+mental+health+evaluation+2010..2025+Australia"

in 53.17 milliseconds.