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• NextGen Consortium: The iPSCORE (iPSC Collection for Omic Research) Resource for Studying the Impact of Genetic Variation on Molecular Phenotypes

  The iPSC Collection for Omic Research (iPSCORE) Resource was created as part of the Next-Gen Consortium funded by NHLBI. The overarching purpose of the resource is to provide a large collection of human induced pluripotent stem cells (iPSCs) for use in studying the impact of genetic variation on molecular and physiological phenotypes. The resource has been used in a number of studies in the Dr. Kelly A. Frazer's Lab examining both the characteristics of human iPSCs and a variety of iPSC-derived cell types including cardiovascular progenitor cells (iPSC-CVPCs), pancreatic precursor cells (iPSC-PPCs), and retina pigment epithelium cells (iPSC-RPEs). We have shown that the iPSCs, CVPCs, and PPCs are suitable surrogate models to identify genetic factors active in early developmental processes because they exhibit fetal-like molecular properties. A total of 273 individuals have participated in the study, of which 222 have had iPSCs generated from fibroblasts. Of the 273 individuals, 181 are part of 55 families that include 24 monozygotic twin pairs and 5 dizygotic twin pairs, allowing for the incorporation of familial relationships into genetic analyses. Germline DNA has been sequenced from blood or fibroblast samples for all 273 individuals (available through dbGaP phs001325) and other genomic data (RNA-seq, DNA methylation, genotype arrays, ATAC-seq, H3K27ac ChIP-seq, HiC-seq) have been generated from the 222 iPSCs as well as derived cell types (available through dbGaP phs000924). QTL analyses were conducted for multiple omics data types and summary statistics are available through dbGaP phs0001325. Important note: Of the 273 individuals, 268 are consented for general research use and 5 are consented for cardiac research only. For detailed information about iPSCORE Collection including samples, methods used to generate the data, and how to access the datasets visit the Frazer lab website.The 222 well characterized iPSC lines that constitute the iPSCORE resource are available, please contact Dr. Kelly A. Frazer (kafrazer@health.ucsd.edu) if you are interested in obtaining the collection.

  Study phs000924

• CSER: Clinical Implementation of Carrier Testing Using Next Generation Sequencing (NextGen)

  We will investigate the clinical implementation of genome sequencing (GS) for carrier screening to aid reproductive decision-making in adults. The study is organized into three inter-related Projects. The study population will include women and their partners who receive pre-conception testing. In Project 1, we will conduct a Randomized Clinical Trial to test clinical implementation of WGS compared with usual care. We will integrate WGS results with the electronic medical record (EMR), and measure outcomes from patient and physician perspectives. In Project 2, we will perform whole genome sequencing, including validation and interpretation of the identified variants to identify "actionable variants", meaning variants deemed worthy of reporting. This will include a robust approach using a Return of Results Committee (RORC) for determination of reportable results. In Project 3, we will evaluate the ethical and psychosocial implications of expanded carrier screening using WGS for the return of carrier status and secondary findings, and measure the impact on downstream healthcare utilization and cost. Two groups of women are identified through the electronic medical record. The first group has a clinical carrier screening test, usually Cystic Fibrosis (CF), ordered and completed as part of a preconception planning visit. The second group has a carrier screening test, usually CF, performed during pregnancy, they have delivered their baby and are planning a future pregnancy. Eligible women are randomized to either usual care or genome sequencing (GS). Women randomized into the usual care arm have already received their clinical genetic test. These women will not receive genome sequencing. Women in the GS arm will receive their carrier status results for about 700 gene/condition pairs approximately three months after randomization. If there are results to return, women come in for a genetic counseling session. If there are no results, a letter is sent in the mail. Incidental findings (IF) are returned about one month later. As with the carrier status results, all IF are returned in person, and if there are no results a letter is sent in the mail. If a participant is found to be a carrier of an autosomal recessive condition, her male partner is then eligible and invited to participate in the study and receive GS.

  Study phs000927

• GEnomics and Transcriptomics of Human INsulinoma (GETHIN)

  The Genomics and Transcriptomics of Human Insulinoma (GETHIN) The common forms of diabetes - Types 1 and 2 - ultimately result from a deficiency of insulin-producing pancreatic beta cells. The Genomics and Transcriptomics of Human Insulinoma (GETHIN) study was performed in order to identify novel approaches to inducing human pancreatic beta cells to replicate and regenerate. As a corollary, developing drugs that are able to expand human beta cell mass in people with diabetes should reverse diabetes. Unfortunately, identifying druggable pathways that can enhance human beta cell replication has been a major challenge. In 2017, there is only one class of drugs - the harmine analogues - that can induce human beta cells to replicate, and in this case, higher replication rates are desirable. Thus, identifying additional drugs and druggable pathways is a priority in diabetes research. Insulinomas are rare, benign adenomas of the pancreatic beta cell that cause excess insulin production and hypoglycemia: exactly the opposite of Types 1 and 2 diabetes. Beta cell proliferation rates in insulinomas are abnormally high. Thus, the premise for The Genomics and Transcriptomics of Human Insulinoma study is that benign human insulinomas hold the genomic and transcriptomic "recipe", and the repertoire of druggable pathways, that can be exploited to induce regeneration or replication of human beta cells in diabetes. Because, insulinomas are so rare, are almost always benign (non-malignant), and are easily resected by laparoscopic surgery, little attention has been paid to understanding the genomics or transcriptomics of insulinoma. There are at present only three published studies employing next-gen sequencing in insulinoma (PMID:24326773; PMID:25787250; and PMID:25763608). These studies contained 10, 7 and 8 insulinomas, respectively, and highlighted likely mutations in YY1 and MEN1. Our goal was to markedly expand the database and to add RNAseq to these earlier studies. The GETHIN study reports next-gen sequencing on 38 insulinomas, by far the largest series of human insulinomas subjected to next-gen sequencing (see the Selected publications section for reference). This includes paired (genomic plus tumor) whole exome sequencing on 26 human insulinomas (22 sequenced at Mount Sinai, 4 downloaded from Cao et al, PMID:24326773), and 25 sets of RNAseq from insulinomas, some of which also had paired whole exome sequencing, and some of which did not. The insulinoma RNAseq was compared to RNAseq from 22 sets of FACS-sorted normal human beta cells. Since insulinomas are so rare, the 38 insulinomas were collected by several investigators at several institutions over several decades, but most (22 whole exome sets, and all RNAseq) were sequenced at the Icahn School of Medicine at Mount Sinai in New York. The current dataset contains whole exome sequencing and RNAseq on the 11 insulinomas harvested at Mount Sinai. The four from Cao et al can be retrieved from Cao et al PMID:24326773. Fastq files from the remaining 23 insulinomas will be added as the local IRBs and Institutional Certifications are acquired. Complete patient data are provided in our Nature Communications report. Going forward, our intention is to expand this series, with the goal of sequencing 100 human insulinomas. These will be added to dbGaP as they accrue. Paired-end whole exome sequencing (mean usable sequencing depth 79X and 105X for blood and insulinoma, respectively) was performed using an Illumina HiSeq 2500. Insulinoma and sorted normal beta cell RNAseq was performed on Ribozero and polyA paired end libraries using the Illumina HiSeq 2500. Complete sequencing and bioinformatic details are provided in our Nature Communications report. The principal findings from the study are that although each insulinoma has a different set of presumptive driver mutations, the majority converge on genes that are members of the Polycomb Complex, Trithorax Complex and other epigenetic modifying enzymes. In addition, 20% of insulinomas have copy number loss or loss of heterozygosity of all or most of chromosome 11, and the majority display abnormalities in CpG methylation and imprinting control on the imprinted Chr 11 p15.5-15.4 region that contains INS, IGF2, CDKN1C, KCNQ1, and other genes involved in beta cell specification and proliferation.

  Study phs001422

• NextGen Consortium: The iPSCORE (iPSC Collection for Omic Research) Resource for Studying the Impact of Genetic Variation on Molecular and Physiological Phenotypes - Whole Genome Sequence

  The iPSC Collection for Omic Research (iPSCORE) Resource was created as part of the Next-Gen Consortium funded by NHLBI. The overarching purpose of the resource is to provide a large collection of human induced pluripotent stem cells (iPSCs) for use in studying the impact of genetic variation on molecular and physiological phenotypes. The resource has been used in a number of studies in the Dr. Kelly A. Frazer's Lab examining both the characteristics of human iPSCs and a variety of iPSC-derived cell types including cardiovascular progenitor cells (iPSC-CVPCs), pancreatic precursor cells (iPSC-PPCs), and retina pigment epithelium cells (iPSC-RPEs). We have shown that the iPSCs, CVPCs, and PPCs are suitable surrogate models to identify genetic factors active in early developmental processes because they exhibit fetal-like molecular properties.A total of 273 individuals have participated in the study, of which 222 have had iPSCs generated from fibroblasts. Of the 273 individuals, 181 are part of 55 families that include 24 monozygotic twin pairs and 5 dizygotic twin pairs, allowing for the incorporation of familial relationships into genetic analyses.Germline DNA has been sequenced from blood or fibroblast samples for all 273 individuals (available through dbGaP phs001325) and other genomic data (RNA-seq, DNA methylation, genotype arrays, ATAC-seq, H3K27ac ChIP-seq, HiC-seq) have been generated from the 222 iPSCs as well as derived cell types (available through dbGaP phs000924).QTL analyses were conducted for multiple omics data types and summary statistics are available through dbGaP phs0001325.Important note: Of the 273 individuals, 268 are consented for general research use and 5 are consented for cardiac research only.For detailed information about iPSCORE Collection including samples, methods used to generate the data, and how to access the datasets visit the Frazer lab website.The 222 well characterized iPSC lines that constitute the iPSCORE resource are available, please contact Dr. Kelly A. Frazer (kafrazer@health.ucsd.edu) if you are interested in obtaining the collection.

  Study phs001325

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

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

  Study phs000928

• NHLBI TOPMed: GOLDN Epigenetic Determinants of Lipid Response to Dietary Fat and Fenofibrate

  The GOLDN study was initiated to assess how genetic factors interact with environmental (diet and drug) interventions to influence blood levels of triglycerides and other atherogenic lipid species and inflammation markers (registered at clinicaltrials.gov, number NCT00083369). The study recruited Caucasian participants primarily from three-generational pedigrees from two NHLBI Family Heart Study (FHS) field centers (Minneapolis, MN and Salt Lake City, UT). Only families with at least two siblings were recruited and only participants who did not take lipid-lowering agents (pharmaceuticals or nutraceuticals) for at least 4 weeks prior to the initial visit were included. The diet intervention followed the protocol of Patsch et al. (1992). The whipping cream (83% fat) meal had 700 Calories/m2 body surface area (2.93 mJ/m2 body surface area): 3% of calories were derived from protein (instant nonfat dry milk) and 14% from carbohydrate (sugar). The ratio of polyunsaturated to saturated fat was 0.06 and the cholesterol content of the average meal was 240 mg. The mixture was blended with ice and flavorings. Blood samples were drawn immediately before (fasting) and at 3.5 and 6 hours after consuming the high-fat meal. The diet intervention was administered at baseline as well as after a 3-week treatment with 160 mg micronized fenofibrate. Participants were given the option to complete one or both (diet and drug) interventions. Of all participants, 1079 had phenotypic data and provided appropriate consent, and underwent whole genome sequencing through the Trans-Omics for Precision Medicine (TOPMed) program. Comprehensive phenotypic and pedigree data for GOLDN study participants are available through dbGaP phs000741.

  Study phs001359

• Hepatitis C Antiviral Long-term Treatment Against Cirrhosis (HALT-C)

  Reprinted from http://www.haltctrial.org/ Purpose The Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial is a randomized controlled trial designed to evaluate the safety and efficacy of long-term use of pegylated interferon for the treatment of chronic hepatitis C in patients who failed to respond to previous interferon therapy. The HALT-C Trial was developed to determine whether prolonged interferon therapy altered histological and clinical outcomes in a group of patients who had failed to eradicate hepatitis C virus with previous interferon treatment. Study Hypotheses In patients with chronic hepatitis C and bridging fibrosis who failed to eradicate the virus with previous interferon therapy, long-term treatment with interferon is safe and can prevent progression to cirrhosis. In patients with cirrhosis secondary to chronic hepatitis C who failed to eradicate the virus with previous interferon therapy, long-term treatment with interferon is safe and can reduce the risks of hepatic decompensation or of hepatocellular carcinoma. Study Design 1145 patients with chronic HCV and advanced hepatic fibrosis (Ishak stage 3-6) who failed to respond to previous treatment with interferon were enrolled at 10 clinical centers and entered into a Lead-in phase. They were treated with a combination of pegylated interferon (Pegasys®, Hoffmann-La Roche) 180 µg/week and ribavirin (1000-1200 mg/day) for 24 weeks. Patients who had no detectable HCV-RNA at week 20 continued on combination therapy until week 48. 662 patients who did not clear virus were randomly assigned at week 24 to either continue treatment with pegylated interferon alone (90 µg/week) for an additional 42 months, or to have treatment discontinued. All patients were followed at 3-month intervals following randomization. Liver biopsy was performed at baseline and after 1.5 and 3.5 years of treatment. Because of slower than expected enrollment and the approval by the FDA of peginterferon alfa-2b after the start of the trial, we modified the study protocol in three ways. First, criteria for admission to the trial were liberalized to allow patients to enter the trial with lower platelet and white blood cell counts than had been initially considered safe or tolerable. Second, 151 Lead-in patients and those continuing on therapy after 24 weeks who demonstrated return of viremia during or after their 48-week treatment period (called "Breakthrough" or "Relapse" patients, respectively) were allowed to return to enter the randomized trial. Third, 237 patients treated with peginterferon alfa-2b (or with peginterferon alfa-2a in licensing trials) outside the HALT-C Trial who in other respects met all study criteria, having received the equivalent of Trial Lead-in period therapy, were allowed to enter the long-term trial as "Express" patients. A total 1050 patients were randomized. Those patients who completed Month 48 were offered an "extended follow-up (observation only)" until October 2009. These visits will primarily be to identify outcome events, and to provide information to patients concerning the current status of the trial. Some questionnaires, blood tests, and an ultrasonogram will be performed. Quarterly (every 3 months) Interval history of complications, adverse events Current medications Brief physical examination Laboratory tests: liver panel, CBC, INR, AFP Child-Pugh Score Stored serum Annual Complete physical examination Ultrasound of liver 1.5 years (M24 visit, middle of study) Liver biopsy: formalin fixed histology, frozen liver tissue (subset of patients) 3.5 years (M48, end of study) Liver biopsy: formalin fixed histology, frozen liver tissue (subset of patients) Endoscopy: evaluate esophageal varices and portal hypertension After Month 48 Observation only (no treatment) to determine clinical outcomes Clinic visit every 6 months with current medications, brief PE, liver panel, CBC, AFP, stored Serum Ultrasound of liver every 6 months Outcome Variables Primary outcome variables to be assessed in the two groups of patients include: Development of cirrhosis on liver biopsy (progression of Ishak fibrosis score by 2 points or more) Development of hepatic decompensation, as shown by: Sustained increase in the Child-Turcotte-Pugh score to 7 points or higher Variceal hemorrhage Ascites Spontaneous bacterial peritonitis Hepatic encephalopathy Development of hepatocellular carcinoma Death Secondary outcomes include quality of life, serious adverse events, events requiring dose reductions, and development of presumed hepatocellular carcinoma.

  Study phs000430

• Genetic Basis of Early Onset Bicuspid Aortic Valve Disease

  The study protocol was approved by the Committee for the Protection of Human Subjects at the University of Texas Health Science Center at Houston (HSC-MS-11-0185). Study recruitment began on July 1, 2017, and concluded on March 30, 2022. After written informed consent, we enrolled probands with early onset BAV disease (EBAV), which we defined as individuals with BAV who were under the age of 30 at the time of first clinical event. Clinical events were defined as aortic replacement, aortic valve surgery, aortic dissection, moderate or severe aortic stenosis or aortic regurgitation, large aneurysm (Z > 4.5), or intervention for BAV-related conditions. Those with hypoplastic left heart, known genetic mutations, genetic syndromes, or complex congenital heart disease were excluded. Samples were collected and genotyped as previously reported. For comparison, we analyzed a cohort of older individuals of European ancestry with sporadic BAV disease selected from the International BAV Consortium (BAVGWAS). Phenotypes were derived from record review with confirmation of image data whenever possible [25-26]. The computational pipeline for CNV analysis of Illumina single nucleotide polymorphism (SNP) array data included three independent CNV detection algorithms.GenomeStudio was used to exclude samples with indeterminate sex or more than 5% missing genotypes, and single nucleotide polymorphisms (SNPs) with GenTrain = 0. Principal component analysis was used to remove outliers that did not cluster with European ancestry. Prior to CNV analysis, each dataset was trimmed by selecting a common set of 650,000 SNPs that were genotyped on each of the microarrays used in this study.Three independent algorithms (PennCNV, cnvPartition, and QuantiSNP) were used to generate CNV calls and sample-level quality statistics from SNP intensity data. PennCNV and QuantiSNP were run on Unix clusters and cnvPartition data were exported from GenomeStudio. The analysis was run using default configurations. PennCNV was used to generate QC data and remove CNV calls that intersect with polymorphic genomic regions. Samples that met any of the following criteria were excluded, standard deviation of the LogR ratio (obtained from PennCNV) > 0.35 or number of CNVs > 2 standard deviations above the mean for each data set. CNV calls less than 20 Kilobases in length and/or spanned by fewer than 6 probes were excluded. The overlap function for rare CNVs in PLINK was used to construct CNV regions (CNVRs) after adjacent regions were merged using PennCNV. LogR ratio (LRR) and B allele frequency (BAF) data at CNVRs and calls of interest were visualized in GenomeStudio for validation. For segregation analysis, GenomeStudio was used to determine the presence of CNVs in relatives.A total of 22,014 unselected control Illumina Genotypes obtained from the Database of Genotypes and Phenotypes were analyzed using identical methods (S1 Table). The Wisconsin Longitudinal Study (WLS) includes data on a cohort of 10,300 individuals who graduated from Wisconsin high schools in 1957. The Health and Retirement Study (HRS) includes data on 37,000 individuals aged 50 above from 23,000 households across the United States. Principal component analysis was used to select European ancestry genotypes from these datasets for analysis. Datasets were paired for case-control analysis based on the concordance of log-transformed sample-level quality control statistics (number of CNV calls and standard deviation of logR ratios). Chi-squared or Fisher exact tests were used to compare CNV frequencies in cases and controls.Rare CNV functions in PLINK (v1.7) were used to perform permutation-based burden tests or gene set-based enrichment tests. Case control burden tests were restricted to CNVs that were longer than 110 Kb and less than 0.1% in frequency. CNV overlap functions in PLINK were used to identify rare CNVs that intersect between datasets or involve specific BAV or CHD genes . The list of candidate genes included 190 CHD genes that have strong cumulative evidence to cause BAV or related congenital malformations from human or animal model data. Genome Reference Consortium Human Build 37 was used for CNV annotation [34].

  Study phs003705

• NHLBI TOPMed: The Cleveland Family Study (CFS)

  The Cleveland Family Study (CFS) is one cohort involved in the WGS project. The CFS was designed to provide fundamental epidemiological data on genetic and non-genetic risk factors for sleep disordered breathing (SDB). In brief, the CFS is a family-based study that enrolled a total of 2284 individuals from 361 families between 1990 and 2006. The sample was selected by identifying affected probands who had laboratory diagnosed obstructive sleep apnea. All first degree relatives, spouses and available second degree relatives of affected probands were studied. In addition, during the first 5 study years, neighborhood control families were identified through a neighborhood proband, and his/her spouses and first degree relatives. Each exam, occurring at approximately 4 year intervals, included new enrollment as well as follow up exams for previously enrolled subjects. For the first three visits, data, including an overnight sleep study, were collected in the participants' homes while the last visit occurred in a general clinical research center (GCRC). Phenotypic characterization of the entire cohort included overnight sleep apnea studies, blood pressure, spirometry, anthropometry and questionnaires. The GCRC exam (n=735 selected individuals) included more comprehensive phenotype data on a focused subsample of the larger cohort, to permit linking SDB phenotypes with cardio-metabolic phenotypes, with an interest in identifying genetic loci that are associated with these related phenotypes. In this last round of data collection, a subset of 735 individuals was selected based on expected genetic informativity by choosing pedigrees where siblings had extremes of the apnea hypopnea index (AHI). Participants underwent detailed phenotyping including laboratory polysomnography (PSG), ECG, spirometry, nasal and oral acoustic reflectometry, vigilance testing, and blood and urine collection before and after sleep and after an oral glucose tolerance test. A wide range of biochemical measures of inflammation and metabolism were assayed by a Core Laboratory at the University of Vermont. 994 individuals were sequenced as part of TOPMed Phase 1, including 507 African-Americans and 487 European-Americans. Among the sequenced individuals, 156 were probands with diagnosed sleep apnea, an additional 706 were members of families with probands, and 132 were from neighborhood control families. 298 individuals were sequenced as part of TOPMed Phase 3.5, including 169 African-Americans and 129 European-Americans. Among the newly sequenced individuals, 33 were probands with diagnosed sleep apnea, an additional 214 were members of families with probands, and 51 were from neighborhood control families. Please note: Phenotype and pedigree data are available through "NHLBI Cleveland Family Study (CFS) Candidate Gene Association Resource (CARe)", phs000284.

  Study phs000954

• National Sleep Research Resource (NSRR): Cleveland Family Study (CFS)

  The Cleveland Family Study (CFS) is a family-based study of sleep apnea, consisting of 2,284 individuals (46% African American) from 361 families studied on up to 4 occasions over a period of 16 years. The study began in 1990 with the initial aims of quantifying the familial aggregation of sleep apnea. National Institutes of Health (NIH) renewals provided expansion of the original cohort, including increased minority recruitment, and longitudinal follow-up, with the last exam occurring in February 2006. The CFS was designed to provide fundamental epidemiological data on risk factors for sleep disordered breathing (SDB). The sample was selected by identifying affected probands who had laboratory diagnosed obstructive sleep apnea. All first-degree relatives, spouses and available second-degree relatives of affected probands were studied. In addition, during the first 5 study years, neighborhood control families were identified through a neighborhood proband, and his/her spouses and first-degree relatives. Each exam, occurring at approximately 4-year intervals, included new enrollment as well as follow up exams for previously enrolled subjects. For the first three visits, data, including an overnight sleep study, were collected in participants' homes while the last visit occurred in a general clinical research center (GCRC). Phenotypic characterization of the entire cohort included overnight sleep apnea studies, blood pressure, spirometry, anthropometry and questionnaires. Currently, data of 710 individuals are available for use through BioData Catalyst (with genotype data available through dbGaP).The National Sleep Research Resource (NSRR) is a NIH-supported sleep data repository that offers free access to large collections of de-identified physiological signals and related clinical data from a large range of cohort studies, clinical trials and other data sources from children and adults, including healthy individuals from the community and individuals with known sleep or other health disorders. The goals of NSRR are to facilitate rigorous research that requires access to large or more diverse data sets, including raw physiological signals, to promote a better understanding of risk factors for sleep and circadian disorders and/or the impact of sleep disturbances on health-related outcomes. Data from over 15 data sources and more than 40,000 individual sleep studies, many linked to dozens if not hundreds of clinical data elements, are available (as of Feb. 2022). Query tools are available to identify variables of interest, and their meta-data and provenance.

  Study phs002715