Framingham Heart Study 100K project: genome-wide associations for cardiovascular disease outcomes


Show simple item record Larson, Martin en_US Atwood, Larry en_US Benjamin, Emelia en_US Cupples, L Adrienne en_US D'Agostino, Ralph en_US Fox, Caroline en_US Govindaraju, Diddahally en_US Guo, Chao-Yu en_US Heard-Costa, Nancy en_US Hwang, Shih-Jen en_US et al. en_US 2009-04-13T23:24:27Z 2009-04-13T23:24:27Z 2007 en_US
dc.identifier.citation 2007. "Framingham Heart Study 100K project: genome-wide associations for cardiovascular disease outcomes," BMC Medical Genetics. vol. 8 issue. Suppl 1 . en_US
dc.identifier.uri 10.1186/1471-2350-8-S1-S5 en_US
dc.description.abstract BACKGROUND:Cardiovascular disease (CVD) and its most common manifestations - including coronary heart disease (CHD), stroke, heart failure (HF), and atrial fibrillation (AF) - are major causes of morbidity and mortality. In many industrialized countries, cardiovascular disease (CVD) claims more lives each year than any other disease. Heart disease and stroke are the first and third leading causes of death in the United States. Prior investigations have reported several single gene variants associated with CHD, stroke, HF, and AF. We report a community-based genome-wide association study of major CVD outcomes.METHODS:In 1345 Framingham Heart Study participants from the largest 310 pedigrees (54% women, mean age 33 years at entry), we analyzed associations of 70,987 qualifying SNPs (Affymetrix 100K GeneChip) to four major CVD outcomes: major atherosclerotic CVD (n = 142; myocardial infarction, stroke, CHD death), major CHD (n = 118; myocardial infarction, CHD death), AF (n = 151), and HF (n = 73). Participants free of the condition at entry were included in proportional hazards models. We analyzed model-based deviance residuals using generalized estimating equations to test associations between SNP genotypes and traits in additive genetic models restricted to autosomal SNPs with minor allele frequency [greater than or equal to]0.10, genotype call rate [greater than or equal to]0.80, and Hardy-Weinberg equilibrium p-value [greater than or equal to] 0.001.RESULTS:Six associations yielded p <10-5. The lowest p-values for each CVD trait were as follows: major CVD, rs499818, p = 6.6 x 10-6; major CHD, rs2549513, p = 9.7 x 10-6; AF, rs958546, p = 4.8 x 10-6; HF: rs740363, p = 8.8 x 10-6. Of note, we found associations of a 13 Kb region on chromosome 9p21 with major CVD (p 1.7 - 1.9 x 10-5) and major CHD (p 2.5 - 3.5 x 10-4) that confirm associations with CHD in two recently reported genome-wide association studies. Also, rs10501920 in CNTN5 was associated with AF (p = 9.4 x 10-6) and HF (p = 1.2 x 10-4). Complete results for these phenotypes can be found at the dbgap website association attained genome-wide significance, but several intriguing findings emerged. Notably, we replicated associations of chromosome 9p21 with major CVD. Additional studies are needed to validate these results. Finding genetic variants associated with CVD may point to novel disease pathways and identify potential targeted preventive therapies. en_US
dc.relation.ispartof BMC Medical Genetics en_US
dc.relation.ispartofseries vol. 8 issue. Suppl 1 en_US
dc.title Framingham Heart Study 100K project: genome-wide associations for cardiovascular disease outcomes en_US
dc.type article en_US

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