on November 1, 2007
Published online before print November 1, 2007, doi: 10.1161/ATVBAHA.107.153981
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Submitted on August 16, 2007
Accepted on October 22, 2007
Association of Gene Variants With Incident Myocardial Infarction in the Cardiovascular Health Study
Dov Shiffman *;
From Celera (D.S., L.A.B., C.M.R., J.Z.L., A.R.A., O.I., M.M.L., B.A.Y., J.J.D.), Alameda, Calif; the Department of Biostatistics (E.S.O., T.L., K.R.), School of Public Health and Community Medicine, University of Washington, Seattle; the Cardiovascular Health Research Unit (T.L., B.M.P.), University of Washington, Seattle; the Cardiovascular Research Institute (M.J.M., J.P.K.), University of California San Francisco; The Cleveland Clinic Foundation (S.G.E.), Department of Cardiovascular Medicine, Cleveland, Ohio; the Departments of Pathology and Biochemistry (R.P.T.), College of Medicine, University of Vermont, Burlington; the Departments of Medicine, Epidemiology, and Health Services (B.M.P.), University of Washington, Seattle; and the Center for Health Studies (B.M.P.), Group Health, Seattle, Wash.
* To whom correspondence should be addressed. E-mail: dov.shiffman{at}celera.com.
Objective—We asked whether single nucleotide polymorphisms (SNPs) that had been nominally associated with cardiovascular disease in antecedent studies were also associated with cardiovascular disease in a population-based prospective study of 4522 individuals aged 65 or older.
Methods and Results—Based on antecedent studies, we prespecified a risk allele and an inheritance model for each of 74 SNPs. We then tested the association of these SNPs with myocardial infarction (MI) in the Cardiovascular Health Study (CHS). The prespecified risk alleles of 8 SNPs were nominally associated (1-sided P<0.05) with increased risk of MI in White CHS participants. The false discovery rate for these 8 was 0.43, suggesting that about 4 of these 8 are likely to be true positives. The 4 of these 8 SNPs that had the strongest evidence for association with cardiovascular disease before testing in CHS (association in 3 antecedent studies) were in KIF6 (CHS HR=1.29; 90%CI 1.1 to 1.52), VAMP8 (HR=1.2; 90%CI 1.02 to 1.41), TAS2R50 (HR=1.13; 90%CI 1 to 1.27), and LPA (HR=1.62; 90%CI 1.09 to 2.42).
Conclusions—Although most of the SNPs investigated were not associated with MI in CHS, evidence from this investigation combined with previous studies suggests that 4 of these SNPs are likely associated with MI.
Key words: coronary disease • myocardial infarction • genetics • polymorphisms
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