This article is part of the supplement: The Framingham Heart Study 100,000 single nucleotide polymorphisms resource

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The Framingham Heart Study 100K SNP genome-wide association study resource: overview of 17 phenotype working group reports

L Adrienne Cupples12*, Heather T Arruda1, Emelia J Benjamin1234, Ralph B D'Agostino125, Serkalem Demissie12, Anita L DeStefano123, Josée Dupuis12, Kathleen M Falls6, Caroline S Fox17, Daniel J Gottlieb38, Diddahally R Govindaraju13, Chao-Yu Guo15, Nancy L Heard-Costa13, Shih-Jen Hwang17, Sekar Kathiresan110119, Douglas P Kiel12, Jason M Laramie133, Martin G Larson15, Daniel Levy137, Chun-Yu Liu2, Kathryn L Lunetta12, Matthew D Mailman14, Alisa K Manning2, James B Meigs1516, Joanne M Murabito13, Christopher Newton-Cheh1119, George T O'Connor13, Christopher J O'Donnell1117, Mona Pandey1, Sudha Seshadri13, Ramachandran S Vasan134, Zhen Y Wang14, Jemma B Wilk13, Philip A Wolf13, Qiong Yang12 and Larry D Atwood123

Author Affiliations

1 National Heart Lung and Blood Institute's Framingham Heart Study, Framingham, MA, USA

2 School of Public Health, Boston University, Boston, MA, USA

3 School of Medicine, Boston University, Boston, MA, USA

4 Whitaker Cardiovascular Institute, Boston University, Boston, MA, USA

5 Department of Mathematics and Statistics, Boston University, Boston, MA, USA

6 Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA

7 National Heart, Lung and Blood Institute, Bethesda, MD, USA

8 VA Boston Healthcare System, Boston, MA, USA

9 Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA

10 Cardiovascular Disease Prevention Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA

11 Cardiology Division, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA

12 Hebrew SeniorLife: Institute for Aging Research and Harvard Medical School, Boston, MA, USA

13 Bioinformatics Program, Boston University, Boston, MA, USA

14 National Center for Biotechnology Information, Bethesda, MD, USA

15 General Medicine Division, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA

16 Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA

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BMC Medical Genetics 2007, 8(Suppl 1):S1  doi:10.1186/1471-2350-8-S1-S1

Published: 19 September 2007



The Framingham Heart Study (FHS), founded in 1948 to examine the epidemiology of cardiovascular disease, is among the most comprehensively characterized multi-generational studies in the world. Many collected phenotypes have substantial genetic contributors; yet most genetic determinants remain to be identified. Using single nucleotide polymorphisms (SNPs) from a 100K genome-wide scan, we examine the associations of common polymorphisms with phenotypic variation in this community-based cohort and provide a full-disclosure, web-based resource of results for future replication studies.


Adult participants (n = 1345) of the largest 310 pedigrees in the FHS, many biologically related, were genotyped with the 100K Affymetrix GeneChip. These genotypes were used to assess their contribution to 987 phenotypes collected in FHS over 56 years of follow up, including: cardiovascular risk factors and biomarkers; subclinical and clinical cardiovascular disease; cancer and longevity traits; and traits in pulmonary, sleep, neurology, renal, and bone domains. We conducted genome-wide variance components linkage and population-based and family-based association tests.


The participants were white of European descent and from the FHS Original and Offspring Cohorts (examination 1 Offspring mean age 32 ± 9 years, 54% women). This overview summarizes the methods, selected findings and limitations of the results presented in the accompanying series of 17 manuscripts. The presented association results are based on 70,897 autosomal SNPs meeting the following criteria: minor allele frequency ≥ 10%, genotype call rate ≥ 80%, Hardy-Weinberg equilibrium p-value ≥ 0.001, and satisfying Mendelian consistency. Linkage analyses are based on 11,200 SNPs and short-tandem repeats. Results of phenotype-genotype linkages and associations for all autosomal SNPs are posted on the NCBI dbGaP website at webcite.


We have created a full-disclosure resource of results, posted on the dbGaP website, from a genome-wide association study in the FHS. Because we used three analytical approaches to examine the association and linkage of 987 phenotypes with thousands of SNPs, our results must be considered hypothesis-generating and need to be replicated. Results from the FHS 100K project with NCBI web posting provides a resource for investigators to identify high priority findings for replication.