Jump to: Authorized Access | Attribution | Authorized Requests

Study Description

This substudy phs000724 Framingham DNA Methylation contains DNA methylation raw data only. Summary level phenotypes for the Framingham Cohort study participants can be viewed at the top-level study page phs000007 Framingham Cohort. Individual level phenotype data and molecular data for all Framingham top-level study and substudies are available by requesting Authorized Access to the Framingham Cohort study phs000007.

The risk of cardiovascular disease (CVD) is determined by the complex interaction of multiple genetic and environmental factors. Although genome-wide association studies (GWAS) have been highly successful in unraveling genes and pathways involved in multiple complex traits and diseases, common genetic variation only explains a small proportion of the heritability of these traits. It is believed that epigenetic factors (modifications in how our genes work that are not due to changes in DNA sequence) impact greatly on multiple complex traits. Epigenetic modifications, however, are largely unexplored in cardiovascular disease (CVD), where many of the causal genes are known to be regulated by epigenetic mechanisms, including DNA methylation. We seek to characterize DNA methylation in participants from the Framingham Heart Study in order to characterize the contribution of DNA methylation to CVD and other complex traits. This project, when combined with the vast data resources of the Framingham Heart Study (including gene expression and GWAS), will further the knowledge of CVD prevention, prediction, and therapy.

We propose to investigate DNA methylation in up to Framingham Heart Study Offspring cohort participants from the Offspring cohort who attended a recent clinic visit, provided a blood sample, and consented to genetic research. The Framingham DNA Methylation Initiative will build upon existing data being generated by the SABRe CVD Initiative and the Framingham SHARe GWAS. With the proposed DNA methylation data resource, we will have the ability to study DNA methylation from different perspectives - always leveraging existing resources to advance the scientific value of this investigation.

Project aims:

  1. To assess differences in DNA methylation across the genome, in relation to cardiovascular disease and other phenotypes - leveraging the extensive surveillance for events and comprehensive phenotype characterization in Framingham.
  2. To characterize the relations of site specific DNA methylation to transcription levels across the genome at a gene and exon level -- leveraging the genomic resources of the SABRe CVD Initiative.
  3. To relate lifestyle and environmental exposures (e.g. diet, smoking, obesity, sleep) and other factors (e.g. sex hormone status) to DNA methylation by investigating the locations, levels and frequency of DNA methylation in relation to these traits -- leveraging the phenotypic resources of Framingham.
  4. To relate common genetic variation from GWAS to variable DNA methylation -- leveraging the genetic resources of the Framingham SHARe GWAS.

Authorized Access
Publicly Available Data
Study Inclusion/Exclusion Criteria

Inclusion:

  • Provided informed consent for genetic research
  • Attended Framingham Offspring 8th exam and had buffy coat sample
  • Sufficient DNA quantity and quality for DNA methylation assay

Molecular Data
TypeSourcePlatformNumber of Oligos/SNPsSNP Batch IdComment
DNA Methylation Illumina Infinium HumanMethylation450 BeadChip N/A N/A
Study History

Research milestones of the Framingham Heart Study can be found at http://www.framinghamheartstudy.org/about/milestones.html.

The Generation 1 (or Original) cohort Exam 1 took place between 1948 and 1953. Biennial exams have continued to the present. Exam 29 took place between 2006 and 2007. Exam 30 began in 2008.

The Generation 2 (or Offspring) cohort Exam 1 took place between 1971 and 1975. This cohort on average has been examined every three to four years. However, there was an eight year gap between Exam 1 and Exam 2 and a seven year gap between Exam 7 and Exam 8. Exam 8 took place between 2005 and 2008.

The Generation 3 cohort Exam 1 took place between 2002 and 2005. Exam 2 began in 2008.

The New Offspring Spouse cohort Exam 1 took place between 2003 and 2005. Exam 2 began in 2008.

Selected Publications
Diseases/Traits Related to Study (MeSH terms)
Authorized Data Access Requests
Study Attribution
  • Principal Investigator
    • Daniel Levy, MD. National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
  • Funding Sources
    • DIR research budget. National Institutes of Health, Bethesda, MD, USA.