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Study Description

This study is part of the NHLBI Trans-Omics for Precision Medicine (TOPMed) Whole Genome Sequencing Program. TOPMed is part of a broader Precision Medicine Initiative, which aims to provide disease treatments that are tailored to an individual's unique genes and environment. TOPMed will contribute to this initiative through the integration of whole-genome sequencing (WGS) and other -omics (e.g., metabolic profiles, protein and RNA expression patterns) data with molecular, behavioral, imaging, environmental, and clinical data. In doing so, this program aims to uncover factors that increase or decrease the risk of disease, to identify subtypes of disease, and to develop more targeted and personalized treatments. Two genotype call sets derived from WGS are now available, one called Freeze 4 (GRCh37) and another called Freeze 5b (GRCh38), with largely overlapping sample sets. Information about how to identify other TOPMed WGS accessions for cross-study analysis, as well as descriptions of TOPMed methods of data acquisition, data processing and quality control, are provided in the accompanying documents, "TOPMed Whole Genome Sequencing Project - Freeze 4, Phase 1" and "TOPMed Whole Genome Sequencing Project - Freeze 5b, Phases 1 and 2". Please check the study list at the top of each of these methods documents to determine whether it applies to this study accession.

Participants from the Atherosclerosis Risk in Communities (ARIC) Study, a large population-based longitudinal cohort study, have been included in this Project and whole genome sequencing will be performed to contribute to analyses of early-onset atrial fibrillation and venous thromboembolism. Additional phenotype and genotype data are available for these individuals on dbGaP and can be accessed through the parent ARIC Cohort accession (phs000280.v3.p1). The National Heart, Lung and Blood Institute (NHLBI) Trans-Omics for Precision Medicine (TOPMed) program is designed to generate scientific resources to enhance understanding of fundamental biological processes that underlie heart, lung, blood and sleep disorders (HLBS). It is part of a broader Precision Medicine Initiative, which aims to provide disease treatments that are tailored to an individual's unique genes and environment. TOPMed will contribute to this initiative through the integration of whole genome sequencing (WGS) and other -omics (e.g., metabolic profiles, protein and RNA expression patterns) data with molecular, behavioral, imaging, environmental, and clinical data. In doing so this program seeks to uncover factors that increase or decrease the risk of disease, identify subtypes of disease, and develop more targeted and personalized treatments. The Whole Genome Sequencing (WGS) Project is part of NHLBI's TOPMed program and serves as an initial step for the larger initiative.

  • Study Type: Case-Control
  • dbGaP estimated ancestry components using GRAF-pop
  • Number of study subjects that have individual level data available through Authorized Access: 13546

Authorized Access
Publicly Available Data (Public ftp)

Connect to the public download site. The site contains release notes and manifests. If available, the site also contains data dictionaries, variable summaries, documents, and truncated analyses.

Study Inclusion/Exclusion Criteria

The inclusion criteria for selection of ARIC study participants for the TOPMed Whole Genome Sequencing Project were full consent or consent for cardiovascular disease-specific research, sufficient DNA for sequencing, and unrestricted use of DNA. Inclusion and exclusion criteria for the individual phenotypes assessed in this study are described below:

A. Venous Thromboembolism project (VTE)

VTE includes both deep vein thrombosis (DVT) in which a blood clot forms in a vein deep in the body, and pulmonary embolism (PE) where a blood clot travels to the lungs and blocks blood flow. Two hundred ninety-nine (299) VTE cases and 3,638 members of the comparison group were chosen for sequencing from the ARIC study. The objectively diagnosed DVT and PE cases were confirmed by venous or pulmonary imaging, pathology examination of the thrombus removed at surgery, or by autopsy.

B. Identification of Common Genetic Variants for Atrial Fibrillation and PR Interval - Atrial Fibrillation Genetics Consortium (AF Gen)

Eighty-four (84) individuals with early-onset atrial fibrillation were selected for sequencing.

Molecular Data
TypeSourcePlatformNumber of Oligos/SNPsSNP Batch IdComment
Whole Genome Sequencing Illumina HiSeq X Ten N/A N/A
Study History

The Atherosclerosis Risk in Communities (ARIC) Study is described below:

The ARIC study is a prospective longitudinal investigation of the development of atherosclerosis and its clinical sequelae in which 15,792 individuals aged 45 to 64 years were enrolled at baseline. At the inception of the study in 1986-1989, the participants were selected by probability sampling from four communities in the United States: Forsyth County, North Carolina; Jackson, Mississippi (African-Americans only); the northwestern suburbs of Minneapolis, Minnesota; and Washington County, Maryland. Four examinations have been carried out at three-year intervals (exam 1, 1987-1989; exam 2, 1990-1992; exam 3, 1993-1995; exam 4, 1996-1998), and subjects are contacted annually to update their medical histories between examinations. A second component of the study involves community surveillance of morbidity and mortality by abstracting hospital records and death certificates and investigating deaths that take place outside of hospitals.

Selected publications
Diseases/Traits Related to Study (MESH terms)
Links to Related Resources
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