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Study Description

This substudy phs000363 Framingham SABRe contains expression data. 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.

Systems Approach to Biomarker Research in Cardiovascular Disease in the NHLBI's Framingham Heart Study: The SABRe CVD Initiative

The NHLBI's Framingham Heart Study (FHS), one of the world's preeminent observational study settings, is devoted to increasing scientific knowledge by establishing a public resource of data and samples. For nearly 60 years, the people of Framingham have generously volunteered their time to this high-profile study and remain deeply committed to its success. The Systems Approach to Biomarker Research in Cardiovascular Disease Initiative (SABRe CVD Initiative) will generate extensive biomarker data from 7000 FHS participants using multiple high throughput platforms including immunoassays, proteomics, metabolomics/lipomics, and gene expression and microRNA profiling. SABRe will generate thousands of new biomarkers from each participant, with data deposited with the NCBI and linked to the extensive phenotype and genotype data already in an NCBI data repository (as part of the NHLBI SHARe Genome-wide Association Project). All data from the SABRe, SHARe, and the nearly 60 years of phenotypic data from the FHS will be integrated into a massive resource that will be accessible to the outside scientific community in a manner consistent with the informed consent preferences of the Framingham participants.

SABRe CVD Projects

  • Project 1: Discovery proteomics and metabolomics/lipomics in case-control studies of subclinical atherosclerosis, metabolic syndrome (300 cases, 300 controls), and predicting new cardiovascular events using samples obtained prior to event (150 cases, 300 controls).
  • Project 2: Immunoassays of 180 circulating protein biomarkers of atherosclerosis and metabolic syndrome in 7400 FHS participants.
  • Project 3: Gene expression profiling of WBC derived RNA to characterize the genomic signatures of atherosclerosis and metabolic syndrome in 5000-7000 FHS participants (lab work to take place at NHLBI Core Microarray Lab).
  • Project 4: MicroRNA profiling of WBC derived RNA to characterize microRNA regulation of gene expression and the relations of microRNA to clinical traits and diseases. microRNA profiling will be conducted in 5000-7000 FHS participants.

The SABRe Initiative is a state-of-the-art research enterprise to advance personalized medicine through biomarker discovery and validation. This project holds great promise for identifying mechanisms of disease and promoting the development of new diagnostics and therapeutics for diseases of high impact.

The specific aims for SABRe CVD are as follows:
1. To identify the biomarker signatures of atherosclerosis as determined by: a) aortic and coronary calcification on CT (data available in 3500 people), b) aortic plaque burden by MRI (n=2000), c) carotid intimal-medial thickness by ultrasound (n=3500), d) clinical atherosclerotic CVD (n=500), and e) the dynamic balance between arterial calcification and bone demineralization (n=3500).

2. To identify the biomarker signatures of metabolic risk factors related to cardiovascular risk: a) systolic and diastolic blood pressure (n=7000), b) body mass index (n=7000) and visceral adiposity by CT (n=3500), c) dyslipidemia (lipid levels, n=7000), and d) impaired fasting glucose, diabetes, and insulin resistance (glucose and insulin levels, n=7000).

3. To identify genomic convergence (convergence of signals from genetic variation and gene expression) with SABRe biomarker levels and clinical traits and diseases.

To accelerate the research opportunities for gene expression experiments from SABRe CVD Project 3, we front-loaded a CVD case-control study at the beginning of the laboratory work. In doing this, we anticipated that this effort would lead to early discoveries and publications.

The CVD case-control study includes 221 matched CVD case-control pairs. Cases were defined on the basis of a hospital-based diagnosis of atherosclerotic CVD (recognized MI, coronary revascularization, or atherothrombotic stroke).

  • Study Weblink: The Framingham Heart Study
  • Study Type: Case-Control
  • Number of study subjects that have individual level data available through Authorized Access: 0

Authorized Access
Publicly Available Data (Public ftp)

Note: Access to publicly available data is available on the public ftp site for study phs000007.v14.p6.

Study Inclusion/Exclusion Criteria

Cases and controls with CVD events at FHS Offspring Exam 8 were matched on age, sex, smoking, and statin use

Endpoint Cases Controls
Coronary disease 190 190
      *MI       *99       *99
      *CABG-bypass       *43       *43
      *PTCA-stent       *48       *48
ABI-stroke 31 31
Total CVD 221 221

Total CVD: Clinical characteristics of the CVD cases and matched controls are provided in the table below

Category Cases (N=221) Controls (N=221)
Mean age 71 71
Mean systolic BP 129 131
Mean diastolic BP 69 73
Mean total cholesterol 152 174
Mean HDL 48 53
Mean triglyceride 126 115
Mean BMI 28.9 28.7
Mean glucose 115 110
Hypertensive meds 186 134
Cholesterol meds 204 150
Diabetes meds 53 41

Molecular Data
TypeSourcePlatformNumber of Oligos/SNPsSNP Batch IdComment
Gene Expression Affymetrix GeneChip Human Exon 1.0 ST Array 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
  • Co-Principal Investigator
    • Christopher O'Donnell, MD. National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA
  • Principal Investigator-Bioinformatics
    • Peter J. Munson, PhD. Center for Information Technology, National Institutes of Health, Bethesda, MD, USA
  • Principal Investigator-Lab Operation
    • Nalini Raghavachari, PhD. National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA
  • Principal Investigator-Statistics
    • Martin G. Larson, SD. Department of Mathematics, Boston University, Boston, MA, USA
  • Investigators
    • Roby Joehanes, PhD. National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA
    • Sai-xia Ying, PhD. Center for Information Technology, National Institutes of Health, Bethesda, MD, USA
    • Andrew Johnson, PhD. National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA
  • Funding Source
    • Division of Intramural Research. National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA