NHLBI TOPMed: Genomic Activities such as Whole Genome Sequencing and Related Phenotypes in the Framingham Heart Study

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.]]>
TOPMed Whole Genome Sequencing Methods: Freeze 9Aptamer Proteomic Profiling Lab Assay (blood), Generation 3 Exam 2: Coding ManualAptamer Proteomic Profiling Lab Assay (blood), Generation 3 Exam 2: DescriptionAptamer Proteomic Profiling Lab Assay (blood), Generation 3 Exam 2: ProtocolAptamer Proteomic Profiling Lab Assay (blood), Generation 3 Exam 2: Version InfoTOPMed Whole Genome Sequencing Methods: Freeze 10The 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.]]>
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.]]>