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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, Freeze 8 (GRCh38) and Freeze 9b (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 8, Phases 1-4" and "TOPMed Whole Genome Sequencing Project - Freeze 9b, Phases 1-4". Please check the study list at the top of each of these methods documents to determine whether it applies to this study accession.

The Framingham Heart Study (FHS) is a prospective cohort study of 3 generations of subjects who have been followed up to 65 years to evaluate risk factors for cardiovascular disease. Its large sample of ~15,000 men and women who have been extensively phenotyped with repeated examinations make it ideal for the study of genetic associations with cardiovascular disease risk factors and outcomes. DNA samples have been collected and immortalized since the mid-1990s and are available on ~8000 study participants in 1037 families. These samples have been used for collection of GWAS array data and exome chip data in nearly all with DNA samples, and for targeted sequencing, deep exome sequencing and light coverage whole genome sequencing in limited numbers. Additionally, mRNA and miRNA expression data, DNA methylation data, metabolomics and other 'omics data are available on a sizable portion of study participants.

This project will focus on deep whole genome sequencing (mean 30X coverage) in ~4100 participants and imputed to all with GWAS array data to more fully understand the genetic contributions to cardiovascular, lung, blood and sleep disorders. Also available are aptamer proteomic profiling, RNAseq and 850K array DNA methylation data that predominantly overlap with participants with WGS data.

Comprehensive phenotypic and pedigree data for study participants are available through dbGaP phs000007.

Authorized Access
Publicly Available Data (Public ftp)
Study Inclusion/Exclusion Criteria

The inclusion criteria for selection of participants for the FHS study were full informed consent and sufficient DNA for sequencing. For WGS and related projects, we focused on selecting individuals informative in families for sequencing, using ExomePicks.

Study History

The Framingham Heart Study is a prospective longitudinal investigation of the development of atherosclerosis and its clinical sequelae. Study participants were recruited at three time periods. The study was initiated in 1948-50 with the recruitment of 5209 individuals ages 28-62 (including some spouse pairs, parent-offspring pairs and siblings) for the purpose of investigating the multiple factors involved in the development of cardiovascular disease. This group, known as the Original Cohort, has been examined every two years with a total of thirty-two examinations to date. In 1971-1975, offspring of the Original Cohort and the offspring spouses were recruited to examine among other goals the familial components of cardiovascular disease and its risk factors. In 2002-2005, the third generation (children of the Offspring and grandchildren of the Original Cohort) was recruited. The Offspring Cohort totaled 5124 and the Third Generation totaled 4095 at recruitment and have been examined every 4 to 8 years. The Offspring Cohort now has 9 examinations completed and the Third Generation has 2 examinations completed. Additionally, there are two minority cohorts totaling ~900 study participants that have been followed since the mid-1990s.

Selected publications
Diseases/Traits Related to Study (MeSH terms)
Links to Related Resources
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See research articles citing use of the data from this study
Study Attribution
  • Principal Investigator
    • Vasan Ramachandran. Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
  • Co-Investigators
    • Martin G. Larson. Framingham Heart Study, Boston University, Boston, MA, USA.
    • Nancy Heard-Costa. Framingham Heart Study, Boston University, Boston, MA, USA.
  • Funding Source
    • National Institutes of Health, Bethesda, MD, USA.