Search Results - EGA European Genome-Phenome Archive

NHLBI Recipient Epidemiology Donor Evaluation Study (REDS)-III - Brazil Sickle Cell Disease Cohort (REDS-BSCDC)

The Recipient Epidemiology and Donor Evaluation Study (REDS)-III program established a Brazilian Sickle Cell Disease (SCD) Cohort to identify molecular determinants of response to transfusions, alloimmunization and risk factors associated with HIV infection. The Brazil population presents a complex admixture of African, European, Asian and Indigenous heritage and will provide insights into genetic, demographic, social, and healthcare system determinates of SCD outcomes. The REDS-III Brazil SCD cohort began in the Fall of 2013 and aimed to: Establish a cohort of SCD patients with a comprehensive centralized electronic database of detailed clinical, laboratory and transfusion information, as well as establish a repository of blood samples to support biological studies relevant to SCD pathogenesis and transfusion complications; Characterize changes in markers of inflammation in response to transfusion by analyzing chemokine/cytokine panels in serial post transfusion specimens; Identify single nucleotide polymorphisms (SNPs) that contribute to the risk of red blood cell alloimmunization in SCD by performing a genome-wide association (GWA) study in transfused SCD patients; Characterize risk of HIV and HIV outcomes in the Brazilian SCD population and compare SCD outcomes among HIV sero-positive and sero-negative SCD patients.

Study phs001972

Biological Determinants of Peritoneal Dialysis Outcomes

Peritoneal Dialysis (PD) is a technique for treating kidney failure where fluid is instilled into the body's peritoneal cavity. Fluid and solutes travel across the peritoneum, and this is critical to successful PD. Studies have shown that certain demographic and clinical variables explain a small part of the variability in baseline peritoneal solute transfer rate and water transfer function across the peritoneum. This study sought to identify the common genetic variants associated with the baseline peritoneal function in patients starting treatment with PD and change in function upon treatment with PD. This study has two specific aims: Aim 1: To identify and validate genetic loci that influence the peritoneal solute transfer rate (PSTR) at start of PD. Aim 2: To identify and validate genetic loci in pre-specified biologic pathways with change in peritoneal ultrafiltration capacity. This study incorporates data from participants' peritoneal solute transfer rate in their first ever peritoneal equilibrium test (PET) and changes in the transfer of water across the peritoneal membrane over time in a sub-group of participants, demographic information, and results from laboratory analysis of DNA, blood, and dialysate. This study comprises patient populations from pre-existing biorepositories in Europe, and prospectively enrolled participants in United States, Canada, United Kingdom, and Australia. Clinical data related to the participants' peritoneal solute transfer rate from their first ever Peritoneal Equilibrium Test (PET), demographic information, and change in ultrafiltration capacity over time, are correlated with various genetic markers of interest. For individuals enrolled prospectively, blood and dialysate were collected at the first study visit. Annually, subjects either underwent a PET as standard of care or perform an additional 4-hour dwell as part of the study. These subsequent measures were utilized to determine change in ultrafiltration capacity over time. Inclusion criteria included adults over the age of 20 who are able to provide consent and had a record of a PET within 6 months of starting PD. Subjects with missing outcome data and that did not pass genotyping QC were excluded. Genotyping was performed in two batches using the Illumina InfiniumOmni2-5-8v1-3_A1 array with 2,372,784 single nucleotide variants (SNVs) in the first batch (n=1957). The second genotyping batch (n=1053) was on the InfiniumOmni2-5-8v1-4_A1 array with 2,382,209 SNVs. Imputation was performed using the Michigan Imputation Server and the HRC1.1 genotype reference. The Institutional Review Board of the University of Washington has “dbGaP-certified” the consent forms used to enroll participants in Australia, Canada, and United States and the genotype-phenotype data from the participants (n=827) deposited in the public repository. Furthermore, it has been determined that under the EU-GDPR regulations, depositing data of participants enrolled in UK, Belgium, and Sweden (n=2,023) into dbGaP “serves no lawful purpose” as the consent form used for enrolling participants did not obtain explicit permission for depositing data in a public repository.

Study phs002996

CIDR: The Role of Rare Coding Variation in Prostate Cancer in Men of African Ancestry - RESPOND Project 2

In RESPOND Project 2, we seek to identify rare genetic factors that are associated with prostate cancer (PCa) risk and aggressiveness in men of African ancestry (AA). We will conduct exome sequencing of 15,000 prostate cancer cases and 5,000 controls from the RESPOND cohort and the African Ancestry Prostate Cancer Consortium (AAPC) with cases selected based on risk categories: high-risk (stage T3/T4 or Gleason 8+ or PSA>20 ng/ml), intermediate-risk (stage T2b/T2c or Gleason 7 or PSA 10-20 ng/ml) and low-risk disease (stage T1/T2a and Gleason ≤ 6 and PSA<10 ng/ml). We expect the findings from this Project to significantly advance knowledge of susceptibility to aggressive PCa and racial/ethnic disparities in PCa risk, and to guide the development of future preventive, early detection and prognostic measures for AA men. The first phase of the study will include exome sequence data for approximately 7,500 cases and 5,000 controls from AAPC. The second phase of the study will include exome data for 5,000 cases from RESPOND and AAPC.ACKNOWLEDGMENTS and CONTRIBUTING SITES Multiethnic Cohort (MEC): The MEC and the genotyping in this study were supported by National Institutes of Health (NIH) grants CA63464, CA54281, CA1326792, CA148085, and HG004726. Cancer incidence data for the MEC and Los Angeles Study of Aggressive Prostate Cancer (LAAPC) studies have been collected by the Los Angeles Cancer Surveillance Program of the University of Southern California with federal funds from the National Cancer Institute (NCI)/NIH/Department of Health and Human Services (DHHS) under Contract No. N01-PC-35139, and the California Department of Health Services as part of the state-wide cancer reporting program mandated by California Health and Safety Code Section 103885, and grant 1U58DP000807-3 from the Centers for Disease Control and Prevention (CDC). Ghana Prostate Study (GPS): The Ghana Prostate Study was funded by the Intramural Program of the NCI/NIH/DHHS under Contract No. HHSN261200800001E. Men of African Descent and Carcinoma of the Prostate (MADCaP): We thank all MADCaP study participants. This work is a product of the MADCaP network. This work was supported by NCI/NIH grant U01CA184374 to Timothy Rebbeck and National Institute of General Medical Sciences (NIGMS) MIRA grant R35GM133727 to Joseph Lachance. Additional funding includes a seed grant from the Integrated Cancer Research Center at Georgia Institute of Technology. UGANDA: The UGANDA study was supported by NIH grant R01CA165862. Southern Community Cohort (SCCS) is funded by NIH grant CA092447. SCCS sample preparation was conducted at the Epidemiology Biospecimen Core Lab that is supported in part by the Vanderbilt Ingram Cancer Center (CA68485). Data on SCCS cancer cases were provided by Alabama Statewide Cancer Registry, Kentucky Cancer Registry, Office of Cancer Surveillance at Tennessee Department of Health, Florida Cancer Data System, Central Cancer Registry at North Carolina Division of Public Health, Georgia Comprehensive Cancer Registry, Louisiana Tumor Registry, Mississippi Cancer Registry, South Carolina Central Cancer Registry, Virginia Cancer Registry at Virginia Department of Health, and Cancer Registry at Arkansas Department of Health. The Arkansas Central Cancer Registry is fully funded by a grant from National Program of Cancer Registries (NPCR)/Centers for Disease Control and Prevention (CDC). Data on SCCS cancer cases from Mississippi were collected by the Mississippi Cancer Registry which participates in the NPCR/CDC. The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the CDC or the Mississippi Cancer Registry. Karuprostate: The Karuprostate study was supported by the French National Health Directorate and by the Association pour la Recherche sur les Tumeurs de la Prostate. Séverine Ferdinand, Marc Romana. The North Carolina - Louisiana Prostate Cancer Project (PCaP) is carried out as a collaborative study supported by the Department of Defense contract DAMD 17-03-2-0052. The authors thank the staff, advisory committees and research subjects participating in the PCaP study for their important contributions. We would also like to acknowledge the UNC BioSpecimen Facility and the LSUHSC Pathology Lab for our DNA extractions, blood processing, storage and sample disbursement (https://genome.unc.edu/bsp). Gene-Environment Interaction in Prostate Study (GECAP) was supported by NIH grant ES011126. King County Prostate Cancer Study (KCPCS) was supported by NIH grants CA056678, CA082664, and CA092579, with additional support from the Fred Hutchinson Cancer Research Center. We thank the participants in these studies, and Ms. Suzanne Kolb for help with study management. The Los Angeles Study of Aggressive Prostate Cancer (LAAPC) was funded by grant 99-00524V-10258 from the Cancer Research Fund, under Interagency Agreement #97-12013 (University of California contract #98-00924V) with the Department of Health Services Cancer Research Program. Cancer incidence data for the MEC and LAAPC studies have been collected by the Los Angeles Cancer Surveillance Program of the University of Southern California with Federal funds from the NCI/NIH/DHHS under Contract No. N01-PC-35139, and the California Department of Health Services as part of the state-wide cancer reporting program mandated by California Health and Safety Code Section 103885, and grant 1U58DP000807-3 from the CDC. Prostate Cancer Studies at MD Anderson (MDA) was supported by grants CA68578, ES007784, DAMD W81XWH-07-1-0645, and CA140388.

Study phs002637

BC Cancer, part of the Provincial Health Services Authority, Technology Development Office, Data Access Committee (PHSA TDO DAC)

Dac EGAC00001003254

DAC Department of Neurology, TUM University Hospital, Technical University of Munich, School of Medicine and Health

Dac EGAC00001003508

eMERGE Network Phase III: HRC SNV and 1000 Genomes SV Imputed Array Data of 105,000 Participants

The Electronic Medical Records and Genomics (eMERGE) Network is a National Institutes of Health (NIH)-organized and funded consortium of U.S. medical research institutions. The primary goal of the eMERGE Network is to develop, disseminate, and apply approaches to research that combine biorepositories with electronic medical record (EMR) systems for genomic discovery and genomic medicine implementation research. eMERGE was announced in June 2007 and began its third phase in September 2015. eMERGE Phase III (June 2015 - June 2020) consists of 10 study sites, two central sequencing and genotyping facilities, and a coordinating center. Included in this study are: Human Reference Consortium (HRC) single nucleotide variants and 1000 Genomes structural variants imputed array data of 105,108 eMERGE participants from nine Phase III study sites and three Phase II study site collaborators. Corresponding demographics, body mass index measurements. Case/control status for the following phenotypes: Abdominal aortic aneurysm; Ace-Inhibitor/Cough; Attention Deficit Hyperactivity Disorder; Age-related macular disease; Appendicitis; Asthma; Atopic Dermatitis; Autism; Benign Prostatic Hyperplasia; Carotid artery disease as a Quantitative Measure; caMRSA; Cataract; Clostridium difficile colitis; Extreme Obesity; Chronic Kidney Disease; Chronic Kidney Disease and Type 2 Diabetes; Chronic Kidney Disease, Type 2 Diabetes and Hypertension; Colon Polyps; Cardiorespiratory Fitness; Dementia; Diverticulosis; Diabetic retinopathy; Gastroesophageal Reflux Disease; Glaucoma; Height; Heart failure; Hypothyroidism; Lipids; Ocular hypertension; Peripheral Arterial Disease; QRS duration; Red blood cell indices; Remission of Diabetes after ROUX-EN-Y gastric bypass surgery; Resistant hypertension; MACE while on Statins; Type 2 Diabetes; Venous Thromboembolism; White blood cell indices; and Zoster virus infection. Study sites and participants include: Boston Children's Hospital: The Gene Partnership (TGP) is a prospective longitudinal registry at Boston Children's Hospital (BCH) to study the genetic and environmental contributions to childhood health and disease, collect genetic information on a large number of children who have been phenotyped, and implement the Informed Cohort and the Informed Cohort Oversight Board (ICOB). The term "The Gene Partnership" reflects a partnership between researchers and participants. Children seen at BCH are offered enrollment, as are their parents and siblings. DNA is collected on all enrollees. BCH has a comprehensive EMR system, and virtually all inpatient and outpatient data are captured electronically. Clinical data in the BCH EMR is loaded in the i2b2 data warehouse which is available to investigators. Cases, phenotypes, and covariates are ascertained using the i2b2 database. Participants at BCH in TGP have consented to receive any research result and/or incidental finding that arises from studies using TGP that is approved by the Informed Cohort Oversight Board (ICOB) and is in accordance with the participants'preferences;results are returned through the Personally Controlled Health Record (PCHR). BCH and Cincinnati Children's Hospital Medical Center (CCHMC) have partnered as the Pediatric Alliance for Genomic and Electronic Medical Record (EMR) Research (PAGER) site for the eMERGE Phase II network for pediatric institutions, and the cohort for eMERGE at BCH is TGP. Children's Hospital of Pennsylvania (CHOP): The Center for Applied Genomics (CAG) at the Children's Hospital of Philadelphia (CHOP) is a high-throughput, highly automated genotyping and sequencing facility equipped with state-of-the-art genotyping and sequencing platforms. Children who are treated at the Children's Hospital Healthcare Network and their parents may be eligible to take part in a major initiative to collect more than 100,000 blood samples, covering a wide range of pediatric diseases. A large majority of participants consenting to prospective genomic analyses also consent to analysis of their de-identified electronic health records (EHRs). EHRs are longitudinal, with a mean duration of 6.5 years. Cincinnati Children's Hospital Medical Center/Boston's Children's Hospital (CCHMC/BCH): Cincinnati Children's Hospital Medical Center (CCHMC) is a pediatric institution dedicated to improving health and welfare of children and to the discovery and practical application of new genomic information to the ordinary care of children. CCHMC brings an extraordinary faculty to eMERGE III who are committed to gain a better understanding of the genesis of disease and to elucidate the mechanisms of diseases that afflict children, specifically pediatric disease phenotypes that will leverage the available eMERGE adult genomic data and electronic medical records (EMRs) to discover meaningful use results. Generation of EMR phenotype algorithms, informed by natural language processing, using heuristic and machine learning methods is ongoing. CCHMC has developed tools to evaluate adolescent return of results preferences, examined the ethical and legal obligations and potential to reanalyze results, and developed clinical decision support for phenotyping, test ordering, and returning sequencing results. The success of these eMERGE III studies is enhanced by the ongoing institutional investment made in the CCHMC Biobank, the comprehensive EMR (EPIC), the i2b2 de-identified medical record data warehouse, and hundreds of faculty and senior staff who make genomics or informatics an active focus of their research. Columbia University: Columbia University Medical Center/New York Presbyterian (CUMC/NYP) Hospital system is one of the nation's largest and most comprehensive hospital systems with over 2 million inpatient and outpatient yearly visits that serves a racially and ethnically diverse urban patient population. The Columbia University GENomic Integration with EHR (GENIE) research study contributed and shared phenotype and genotype data for individuals who were recruited as part of a diverse array of initiatives within the hospital, including Northern Manhattan Study (NOMAS), Pediatric Cardiac Genomic Consortium (PCGC), Caribbean Hispanics with Familial and Sporadic Late Onset Alzheimer's disease (AD), Alzheimer's Disease Sequencing Project (ADSP), and Genetics of Chronic Kidney Disease study. Some of these individuals had kidney or neurological problems, some were healthy adult volunteers with self-reported health status information from the medically underserved Northern Manhattan community, and others were pediatric patients with cardiac conditions. For the kidney disease cohort, patients with the diagnosis of Chronic Kidney Disease (CKD) and healthy controls were recruited to the Columbia University CKD biobank. For the NOMAS cohort, eligible participants were stroke-free, were 40 years old, and resided for at least 3 months in a Northern Manhattan household with a telephone. The PCGC study recruited parent-offspring trios with pediatric probands diagnosed with congenital heart defects (CHD). For the Caribbean Hispanics with Alzheimer's disease project, individuals from families affected by AD and with sporadic AD were recruited, along with unrelated controls. Samples for the ADSP study have been selected from well-characterized cohorts of individuals with AD diagnosis. Geisinger Health System: 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 patients 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. Partners Health Care (Harvard): The Partners HealthCare Biobank is a large research program designed to help researchers understand how people's health is affected by their genes, lifestyle, and environment. This large research data and sample repository provides access to high-quality, consented blood samples to help foster research, advance our understanding of the causes of common diseases, and advance the practice of medicine. For the Partners research community (Massachusetts General Hospital and Brigham and Women's Hospital), the Biobank provides: Banked samples (plasma, serum, and DNA) collected from consented patients Blood samples that were discarded after clinical testing in the Crimson Cores maintained in the Brigham and Women's Hospital and Massachusetts General Hospital Pathology Departments Sample handling and preparation services Link to the biobank data to the Partners Research Patient Data Registry (RPDR) a research instance of our electronic clinical chart Data access through our research portal. To date, over 60,000 Partners patients have given their consent to enroll, give a blood sample, receive research results and agreed to be re-contacted for additional research studies. The Biobank has enabled Partners investigators to compete for nationally recognized grants in personalized medicine such as a clinical electronic Medical Records and Genomics network (eMERGE) site and the national All of US program. The Biobank currently supports over 120 Partners investigators and over 100 million dollars in NIH research. Kaiser Permanente Washington with the University of Washington and the Fred Hutchinson Cancer Research Center: KPWA participants were enrolled in the eMERGE Network through the Northwest Institute of Genetic Medicine (NWIGM) biorepository, and provided the appropriate consent to receive clinically relevant genetic results (N~8,073.) NWIGM is based at the University of Washington and co-managed by the University of Washington and KPWA. The purpose of the NWIGM biorepository is to build infrastructure and resources to carry out a broad range of future genetic research. KPWA members enrolled in the biorepository are asked to provide informed consent to providing a DNA sample for storage in the NWIGM biorepository. The consent is purposefully broad to serve the dual purpose of reducing the burden on researchers who wish to use this biorepository and the IRB committees who will be responsible for reviewing these requests in the future. Participants were eligible if aged 50 - 65 years old at the time of their enrollment into the NWIGM repository, living, enrolled in KPWA's integrated group practice, and had completed an online Health Risk Appraisal. The selection algorithm was based on several data sources from the EHR at KPWA. 1) Demographics - participants with self-reported race as Asian ancestry were prioritized and selected to enrich for non-European ancestry. The KPWA eMERGE cohort includes n=1,245 members of Asian ancestry. 2) Participants were also selected for a history of colorectal cancer (n=1,002), in order to allow us to enrich germline pathogenic variants. Essentia Institute of Rural Health, Marshfield Clinic, Pennsylvania State University (Marshfield): The Marshfield Clinic Personalized Medicine Research Project is a population-based biobank in central Wisconsin with more than 20,000 adult subjects who provided written, informed consent to access their medical records and provided a blood sample from which DNA was extracted and plasma and serum stored. In addition to an average of 30 years of medical history data, a questionnaire about environmental exposures, including a detailed food frequency questionnaire, is available to facilitate gene/environment studies. Mayo Clinic: The Mayo Vascular Disease Biorepository is a disease-specific biobank for vascular diseases including peripheral arterial disease (PAD). PAD patients were identified from individuals referred to the non-invasive vascular laboratory for lower extremity arterial evaluation. Since 1997, laboratory findings have been recorded into an electronic database employing an in-house software package for data archiving and retrieval;this data becomes part of the Mayo EMR. Patients referred to the center with suspected PAD undergo a comprehensive non-invasive evaluation including the ankle-brachial index (ABI) - the ratio of blood pressure measured in the upper arms divided by blood pressure measured at the ankles. Controls subjects are identified from patients referred to the Cardiovascular Health Clinic for stress ECG. The prevalence of PAD in patients with normal exercise capacity who do not have inducible ischemia on the stress ECG , was <1%. Data regarding risk factors for atherosclerosis such as diabetes, dyslipidemia, hypertension, and smoking are ascertained from the EMR. Case control study of venous thromboembolism (PI John Heit) Controls from a case control study of pancreatic cancer (PI Gloria Petersen) Mayo Clinic Biobank. Icahn School of Medicine at Mount Sinai School (Mt. Sinai): The Institute for Personalized Medicine (IPM) Biobank Project is a consented, EMR-linked medical care setting biorepository of the Mount Sinai Medical Center (MSMC) drawing from a population of over 70,000 inpatients and 800,000 outpatient visits annually. MSMC serves diverse local communities of upper Manhattan, including Central Harlem (86% African American), East Harlem (88% Hispanic Latino), and Upper East Side (88% Caucasian/white) with broad health disparities. IPM Biobank populations include 28% African American (AA), 38% Hispanic Latino (HL) predominantly of Caribbean origin, 23% Caucasian/White (CW). IPM Biobank disease burden is reflective of health disparities with broad public health impact: average body mass index of 28.9 and frequencies of hypertension (55%), hypercholesterolemia (32%), diabetes (30%), coronary artery disease (25%), chronic kidney disease (23%), among others. Biobank operations are fully integrated in clinical care processes, including direct recruitment from clinical sites, waiting areas and phlebotomy stations by dedicated Biobank recruiters independent of clinical care providers, prior to or following a clinician standard of care visit. Recruitment currently occurs at a broad spectrum of over 30 clinical care sites. Northwestern University: The NUgene Project is a repository with longitudinal medical information from participating patients at affiliated hospitals and outpatient clinics from the Northwestern University Medical Center. Participants'DNA samples are coupled with data from a self-reported questionnaire and continuously updated data from our Electronic Medical Record (EMR) representing actual clinical care events. Northwestern has a state-of-the art, comprehensive inpatient and outpatient EMR system of over 2 million patients. NUgene has broad access to participant data for all outpatient visits as well as inpatient data via a consolidated data warehouse. NUgene participants consent to distribution and use of their coded DNA samples and data for a broad range of genetic research by third-party investigators. Vanderbilt University Medical Center: BioVU, Vanderbilt's DNA databank, was designed as an enabling resource for exploration of the relationships among genetic variation, disease susceptibility, and variable drug responses. BioVU acquires DNA from discarded blood samples collected from routine patient care. The biobank is linked to de-identified clinical data extracted from Vanderbilt's EMR, which forms the basis for phenotype definitions used in genotype-phenotype correlations. BioVU is currently the largest single site DNA collection world-wide, at >235,000 samples as of spring 2017.

Study phs001584

Center for Craniofacial and Dental Genetics (CCDG): Genetics of Orofacial Clefts and Related Phenotypes

The purpose of this study is to investigate the genetics of orofacial clefts (OFCs) in a large study population, and importantly, to incorporate subclinical phenotypic features into these studies. Orofacial clefts (OFCs) comprise a significant fraction of human birth defects (about 1/700 live births (Rahimov et al. 2012) and represent a major public health challenge, as individuals with these anomalies require surgical, nutritional, dental, speech, medical and behavioral interventions, thus imposing a substantial economic and personal burden (Berk and Marazita 2002*). The most common forms include OFCs of the lip alone (CL, Figure 1A), CL plus cleft palate (CL+CP, Figure 1B) or of the palate only (CP, Figure 1C). Individuals born with OFC may have their first surgical repair at age 3 months, but this initial surgery is just the beginning of a lifetime of health burdens. An individual born with an OFC has a hospital use rate increased for most ages (up to 233% increase for children ages 0-10 years and 16% for middle aged adults (Wehby et al. 2012). Healthcare costs for children with OFCs are estimated to be 800% greater compared with their unaffected peers (Boulet et al. 2009). Data from Denmark show that people born with CL with or without CP (CL/P) have an increased mortality up to age 55, which may be attributed to an increased risk of suicide and/or certain cancers (Christensen et al. 2004). The focus of most OFC genetic research has been CL and/or CP. Furthermore, the majority of OFC, i.e. about 70% of CL/P and 50% of CP is considered "nonsyndromic" (Jones 1988), i.e. isolated anomalies with no other apparent cognitive or structural abnormalities. Figure 1 Sample OFC Types A: Bilateral Cleft Lip; B:Cleft Lip plus Cleft Palate; C:Cleft Palate Alone The factors leading to the majority of nonsyndromic OFCs are still unclear, particularly at an individual family level. As is true for many complex traits, substantial progress in gene identification has occurred in the OFC field in the last two years (Dixon et al. 2011; Marazita 2012). Genome Wide Association Studies (GWAS) and sequencing studies to date by our research team and others have focused on genetic risk factors for overt CL/P and CPO-and have been very successful. A major finding from this work is that OFCs exhibit significant genetic heterogeneity, i.e., multiple genetic regions have been implicated (Beaty et al. 2010; Ludwig et al. 2012). Thus, approaches are needed to understand this genetic heterogeneity. Are there GxG interactions at work? Are there subsets of families, each due to a different gene? Our research group has shown that a promising approach to dissect the etiology of OFC is to focus on subclinical phenotypic features within entire cleft families (not just in affected cases, but also in their non-cleft relatives). These subtle features are believed to represent mild manifestations of the same underlying genetic susceptibility responsible for OFCs; as such, their inclusion in case-control and family-based genetic studies can help to clarify and refine the relationship between genotype and phenotype. The study population comprises a large number of families and individuals (~12,000 individuals) from multiple populations worldwide (Caucasians from the US and Europe, Asians from China and the Philippines, Mixed Native American/Caucasians from South America, and Africans from Nigeria and Ethiopia). There are cases, case families (nuclear families and extended kindreds), as well as controls with no history of OFC nor other developmental defects. *Berk NW, Marazita ML (2002) Costs of Cleft lip and Palate: Personal and Societal Implications. In: Wyszynski DF (ed) Cleft Lip and Palate: From Origin to Treatment. Oxford University Press, Inc., New York, pp 458-467.

Study phs000774

Rhode Island Child Health Study (RICHS)

Mother and infant pairs were enrolled in the Rhode Island Child Health Study (RICHS) at the Woman and Infant's Hospital from 2009 through 2014. This population consists of singleton, term infants (≥37 weeks gestation) born without serious pregnancy complications or congenital or chromosomal abnormalities. Given a priority interest to study fetal growth, the RICHS population was oversampled for both large for gestational age (LGA, >90% 2013 Fenton Growth Curve) and small for gestational age (SGA, <10% 2013 Fenton Growth Curve) infants.

Study phs001586

NHLBI TOPMed: Children's Health Study (CHS) Integrative Genomics and Environmental Research of Asthma (IGERA)

The Integrative Genomics and Environmental Research of Asthma (IGERA) Study was proposed to collect immortalized cell lines, RNA, cDNA and DNA from 400 well-characterized subjects who participated in the southern California Children's Health Study (CHS) and to develop an accompanying database for these samples consisting of extensive phenotype, exposure, genome-wide genotype, gene expression, and methylation data. A subset of Hispanic-White participants (n=160) were included in the TOPMed project, including 77 asthma cases and 83 controls.

Study phs001603

Gut 16S rRNA/FINRISK 2002

The main goal of the project is the study the associations between the gut 16S rRNA and human health. The dataset contains data for FINRISK 2002 participants (a random sample of individuals living in six geographic areas in Finland) who underwent fecal sampling.

Study EGAS50000000198

Comprehensive survey for the construction of an integrated database of food, gut microbiome, and health information (the "Sukoyaka Health Survey")

We conducted a cohort-based study to investigate the association between the genetic background and diet/lifestyle in 59 healthy Japanese. We analyzed some participants living in Nagasaki. Shotgun metagenomic sequencing of fecal microbiome were analyzed.

Study JGAS000681

BM

metabolite levels measured by Brainshake Metabolomics/Nightingale Health metabolic platform (log2)

Dataset EGAD00010002150

Drug screening of patient-derived organoids from colorectal peritoneal metastases

Colorectal cancer (CRC) patients with peritoneal metastases (CRPM) have limited treatment options and the lowest CRC survival rates. We trialed the possibility of organoid directed precision treatment for CRPM patients. CRPM organoids (peritonoids) isolated from patients underwent next-generation sequencing and medium-throughput drug panel testing ex vivo to identify specific drug sensitivities for each patient. We measured the utility of such a service including: success of peritonoid generation, time to cultivate peritonoids, reproducibility of the medium-throughput drug testing, and documented changes to clinical therapy as a result of the testing. Peritonoids were successfully generated and validated from 68% (19/28) of patients undergoing standard care. Genomic and drug profiling was completed within 8 weeks and a formal report ranking drug sensitivities was provided to the medical oncology team upon failure of standard care treatment. This resulted in a treatment change for 2 patients, one of whom had a partial response despite previously progressing on multiple rounds of standard care chemotherapy. The barrier to implementing this technology in Australia is the need for drug access and funding for off-label indications. In conclusion, our approach is feasible, reproducible and can guide novel therapeutic choices in this poor prognosis cohort, where new treatment options are urgently needed. This platform is relevant to many solid organ malignancies.

Study phs002023

CIDR Estrogen Receptor Negative Breast Cancer in African American Women: DNA Methylation, Reproductive Events, and Mammary Epithelial Cell Populations

We conducted methylation profiling of breast tumor DNA from Formalin-Fixed Paraffin-Embedded (FFPE) samples for 1,550 cases from a cohort of Black women from the Black Women’s Health Study (BWHS), the Women’s Circle of Health Study (WCHS), and from the Pathways Study using the Illumina MethylationEPIC array. We will examine differentially methylated loci (DML) between ER+ and ER- tumors, and by age at onset of breast cancer. Combining these data with previously analyzed samples (n=385), we will consider associations between reproductive risk factors and top DML by age at diagnosis and ER status, examining the complex relationships between methylation, tumor and patient characteristics, and reproductive risk factors using structural equation modeling.

Study phs002688

Effect of 28-day administration of Urolithin A to sedentary elderly on muscle gene expression

Urolithin A (UA) is a natural dietary, microflora derived, metabolite shown to stimulate mitophagy and improve muscle health in old animals and pre-clinical models of aging. UA was administered for 28-day in a first-in-human clinical trial to sedentary elderly subjects. Muscle biopsies were collected before the first dosing, and at the end of the 28-day period, under fasted conditions. Gene expression was measured by microarray. Gene-set enrichment analysis of the gene expression data showed that UA increased the transcription of mitochondrial related genesets. These observed effects on mitochondrial biomarkers show that UA induces a molecular signature of improved mitochondrial and cellular health following regular oral consumption in humans.

Study EGAS00001003638

The ClinSeq Project: Piloting Large-Scale Genome Sequencing for Research in Genomic Medicine

ClinSeq is a pilot project to investigate the use of whole-genome sequencing as a tool for clinical research. By piloting the acquisition of large amounts of DNA sequence data from individual human subjects, we are fostering the development of hypothesis-generating approaches for performing research in genomic medicine, including the exploration of issues related to the genetic architecture of disease, implementation of genomic technology, informed consent, disclosure of genetic information, and archiving, analyzing, and displaying sequence data. In the initial phase of ClinSeq, we are enrolling roughly 1000 participants; the evaluation of each includes obtaining a detailed family and medical history, as well as a clinical evaluation. The participants are being consented broadly for research on many traits and for whole-genome sequencing. Initially, Sanger-based sequencing of 300-400 genes thought to be relevant to atherosclerosis is being performed, with the resulting data analyzed for rare, high-penetrance variants associated with specific clinical traits. The participants are also being consented to allow the contact of family members for additional studies of sequence variants to explore their potential association with specific phenotypes. Here, we present the general considerations in designing ClinSeq, preliminary results based on the generation of an initial 826 Mb of sequence data, the findings for several genes that serve as positive controls for the project, and our views about the potential implications of ClinSeq. The early experiences with ClinSeq illustrate how large-scale medical sequencing can be a practical, productive, and critical component of research in genomic medicine. Reprinted from Genome Res. 2009 Sep; 19(9): 1665-1674, with permission from Genome Research, PMID: 19602640.

Study phs000971

RNA-seq FASTQ files studied in Generation of hypoimmunogenic induced pluripotent stem cells by CRISPR-Cas9 system and detailed evaluation for clinical application

This data set contains 12 paired fastq files (RNA-seq) from one wild-type iPS cell, two HLA-KO iPS clones and three CD14+ monocytes differentiated from them. The RNA-seq libraries were generated with Illumina TruSeq Stranded Total RNA library prep kit. The libraries were sequenced with Illumina NovaSeq 6000 in paired-end mode.

Dataset EGAD50000001700

Novel manifestations of immune dysregulation and granule defects in gray platelet syndrome

Gray Platelet Syndrome (GPS) is a rare recessive bleeding disorder resulting from biallelic variants in NBEAL2. As part of a comprehensive evaluation of the phenotype and genotype in 47 patients with GPS, four different blood cell-types (platelets, neutrophils, monocytes, and CD4-lymphocytes) were evaluated using bulk RNA-seq in five patients and five controls. These data are deposited in this archive in FASTQ format.

Dataset EGAD00001005950

National Eye Institute (NEI) Exfoliation Genotyping Study

The overall goal of our research is to elucidate the pathogenesis of exfoliation syndrome and the associated glaucoma, making it possible to implement effective screening and prevention strategies and to develop novel therapies. Cases genotyped for this project are from the Nurses Health Study (NHS), the Health Professionals Follow-up Study (HPFS), the Women's Genome Health Study (WGHS), the Massachusetts Eye and Ear Infirmary (MEEI), Mayo Clinic, the University of Iowa, the University of Miami and Duke University Medical Center. Exfoliation syndrome (XFS) is a common condition that is a major risk factor for high-tension open-angle glaucoma, pre-mature cataract formation, and increased risk of complications during cataract surgery. Previous studies suggest that exfoliation syndrome and the related glaucoma (XFG) are genetically complex, and one gene, LOXL1, has been identified as a major genetic risk factor. LOXL1 variants are found in up to 98% of affected patients; however, these same variants are also present in up to 80% of unaffected individuals, indicating that additional genetic and/or environmental factors are necessary for disease development. Samples genotyped for this study are a case set (1,096 samples) and 24 pedigrees (98 samples). Controls for association analyses are selected from the NEIGHBORHOOD study.

Study phs001053

Whole genome, exome and transcriptome analysis to guide individualized cancer interpretation

Study Design: The Cancer Alliance study was a collaboration of nine academic medical institutions in the New York city area and led by the New York Genome Center. Tumor-normal paired samples were submitted by the institutions for whole genome, whole exome and transcriptome sequencing and bioinformatics analysis at New York Genome Center. Relevant clinical histories were also collected. Raw sequence files were available to all collaborators. Variant call files were analyzed both manually by interpreters at NYGC and by IBM Watson Genome Analytics. This study was approved by a central institutional review board (IRB), Biomedical Research Alliance of New York, and by local IRBs, including Stony Brook University and Northwell Health. The study was supported in part by a grant from the IBM corporation (IBM Watson Health) to the New York Genome Center, New York Genome Center philanthropic funds and Rockefeller University grant # UL1TR000043 from the National Center for Advancing Translational Sciences (NCATS), and the National Institutes of Health (NIH) Clinical and Translational Science Award (CTSA) program. The principal investigator Robert B. Darnell MD, PhD., is a Howard Hughes Medical Institute Investigator. Results: Pending Publication of Analysis of Study Conclusions: Pending Publication of Analysis of Study

Study EGAS00001004013

Research Program on Genes, Environment and Health (RPGEH)

The Kaiser Permanente Research Program on Genes, Environment, and Health (RPGEH) is a resource developed to facilitate research on genetic and environmental factors on common diseases and healthy aging. The RPGEH resource links biospecimens, health surveys, and comprehensive electronic medical records on broadly consented adult members of Kaiser Permanente Medical Care Plan, Northern California Region (KPNC). KPNC is an integrated health care delivery system with a membership of approximately 3.3 million people in northern California. The membership of KPNC is representative of the general population in the 14 county area in which facilities are located, although extremes of income are underrepresented. At the end of 2013, the RPGEH resource included: (1) demographic and behavioral surveys from over 430,000 participants; (2) biospecimens (DNA, serum, plasma, and/or saliva) from over 204,000 participants, including over 13,000 pregnant women; (3) genome-wide genotype data (70 billion SNP genotypes) on over 100,000 participants, including the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort; and (4) the longitudinal electronic medical records of the participants. The RPGEH was developed beginning in 2005 at the Division of Research of Kaiser Permanente Northern California by Catherine Schaefer (Director), Neil Risch (Co-Director), Lisa Croen, Eric Jorgenson, Lawrence Kushi, Charles Quesenberry, Sarah Rowell, Carol Somkin, Stephen Van den Eeden, Larry Walter, and Rachel Whitmer. Funding of the RPGEH was provided to C. Schaefer (PI) and N. Risch (co-PI) by the Wayne and Gladys Valley Foundation, The Ellison Medical Foundation, the Robert Wood Johnson Foundation, Kaiser Permanente Northern California, and the Kaiser Permanente National and Regional Community Benefit Programs. The GERA cohort was funded by a grant from NIH to RPGEH and UCSF (RC2 AG036607; C. Schaefer and N. Risch, PIs). At the time of the award of the RC2 project in late 2009, the RPGEH had established a cohort of about 140,000 individuals who had answered a detailed survey, provided saliva samples for extraction of DNA, and given broad consent for the use of their data in studies of health and disease. Survey and Cohort Recruitment. Initially, the RPGEH developed electronic disease registries to enable identification of phenotypes, using algorithms applied to EMR data. In 2007, the RPGEH mailed a four page survey to 1.9 million adult (≥ 18 years old) members of KPNC who had been members for two years or more, to obtain data on demographic and behavioral factors complementary to the clinical data in the EMR. The survey materials included a cover letter introducing the RPGEH, a two page list of Frequently Asked Questions, and the survey, which included questions on demographic factors such as education, race-ethnicity, income and marital status, dietary factors, physical activity, smoking, and alcohol consumption, as well as reproductive history and reproductive health. Members whose electronic medical records indicated a preference for written communications in Chinese or Spanish received survey materials both in English and a Chinese or Spanish translation. Approximately 400,000 completed surveys were returned. Saliva Sample Collection. Beginning in July 2008, respondents to the survey were asked to sign and return a consent form and authorization for use and disclosure of protected health information. The consent form authorized broad use of biospecimens, survey data, and data from participants' electronic health records for use in studies of genetic and environmental influences on health and disease. Respondents who returned completed consent forms were mailed (Oragene) saliva collection kits; more than 132,000 saliva samples were collected in two years. Completed saliva kits were scanned and archived in a temporary biorepository at the KPNC Division of Research. In late 2009, the RPGEH began collection of saliva samples from the California Men's Health Study (CMHS), a cohort that had been previously assembled in 2002-2003 and had been excluded from the RPGEH survey mailing with the intent of later adding CMHS participants to the assembled RPGEH cohort. The CMHS was developed to facilitate research on prostate cancer and other conditions in older men; the study protocol is described in Enger, et al., 2006. It enrolled and surveyed more than 40,000 men in KPNC, ages 45-69 years, who were members of KPNC during 2002-2003. CMHS men completed two mailed surveys with demographic and behavioral data similar to that of the RPGEH. The data on analogous variables were reconciled and integrated with the data derived from the RPGEH cohort for use in the RPGEH resource. By 2011, RPGEH collected approximately 15,400 saliva samples from men participating in the CMHS. RPGEH Access and Collaborations Website and Procedures. The RPGEH maintains a web portal for inquiries and applications for collaboration and access to data. The url is: https://rpgehportal.kaiser.org/. RPGEH has an application process and an Access Review Committee that reviews applications for collaboration and use. For more information, please contact RPGEH through the website.

Study phs000788

The mutational characterization of adenoid cystic carcinoma

Adenoid cystic carcinoma (ACC) typically emanate from the major and minor salivary glands of the head and neck. ACCs have high rates of perineural invasion, locoregional recurrence, and distant metastasis. Here we report sequencing of 60 tumor/normal pairs and find substantial mutational diversity. On pathway analysis, a significant percentage of mutations involved chromatin remodeling, DNA damage, protein kinase A signaling, and FGF/IGF/PI3K signaling. Whole genome sequencing and FISH confirmed the MYB-NFIB translocation as the main structural variant in ACC. Evaluation of potential driver mutations KDM6A and PIK3CA reveal that specific, observed alterations impart functional consequences. Collectively, our data delineate the ACC mutational landscape and establish a molecular foundation for investigating new therapies for this disease.

Study phs000612

CRISPR-screening identifies mechanisms of resistance to KRASG12C and SHP2 inhibitor combinations in non-small cell lung cancer

Although KRASG12C inhibitors show clinical activity in patients with KRAS G12C mutated NSCLC and other solid tumor malignancies, response is limited by multiple mechanisms of resistance. The KRASG12C inhibitor JDQ443 shows enhanced preclinical antitumor activity combined with the SHP2 inhibitor TNO155, and the combination is currently under clinical evaluation. To identify rational combination strategies that could help overcome or prevent some types of resistance, we evaluated the duration of tumor responses to JDQ443 �� TNO155, alone or combined with the PI3K�� inhibitor alpelisib and/or the CDK4/6 inhibitor ribociclib, in xenograft models derived from a KRASG12C-mutant NSCLC line and investigated the genetic mechanisms associated with loss of response to combined KRASG12C/SHP2 inhibition.

Study JGAS000643

Integrated Genomic Analysis of Chronic Lymphocytic Leukaemia

Chronic lymphocytic leukaemia (CLL) is a frequent and heterogeneous disease whose genetic alterations determining the clinicobiological behaviour are not fully understood. Here, we describe a comprehensive evaluation of the genomic landscape of 452 CLLs and 54 monoclonal B-lymphocytosis (MBL), a precursor disorder. This study provides an integrated portrait of the genomic landscape of CLL, identifies new recurrent mutations acting as drivers of the disease, and suggests clinical interventions which may improve the management of patients with this neoplasia. The data here included was described in the ICGC-CLL manuscript published by Puente et al (Nature 2015). Note that complementary RNA-seq data generated within the IGCG-CLL can be found in EGAS00001000374.

Study EGAS00001001306

A PROSTATE TUMORGRAFT PANEL TO ACCELERATE PRECISION MEDICINE

The management of advanced prostate cancer (PCa) has strongly evolved in the last decade with the introduction of the next generation of androgen receptor pathway inhibitors which have considerably improved patient outcomes. Most recently, the investigation of genomic landscape has provided targetable molecular alterations such as homologous gene DNA repair defects correlated with response to PARP inhibitors. Despite these significant advances, while localized PCa is generally associated with favorable outcome, metastatic PCa is currently considered incurable. For further investigations in precision treatment, the development of preclinical models representing the complex prostate tumor heterogeneity are mandatory. Accordingly, we aimed to establish a resource of patient-derived xenograft (PDX) models that exemplify each phase of this multistage disease for accurate and rapid evaluation of candidate therapies.

Study EGAS00001007033

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

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