02878nas a2200517 4500008004100000022001400041245010500055210006900160260001300229300001000242490000700252520134800259653002201607653000901629653002201638653002101660653004001681653001101721653003801732653001101770653002501781653000901806653002601815653005301841653003601894653003201930653001801962100001801980700002201998700001902020700002402039700001902063700002302082700001902105700001802124700002002142700001702162700002302179700002002202700001802222700002202240700002202262700002102284700002002305856003502325 2008 eng d a1524-463600aAssociation of gene variants with incident myocardial infarction in the Cardiovascular Health Study.0 aAssociation of gene variants with incident myocardial infarction c2008 Jan a173-90 v283 a
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.
10aAfrican Americans10aAged10aAged, 80 and over10aCoronary Disease10aEuropean Continental Ancestry Group10aFemale10aGenetic Predisposition to Disease10aHumans10aLongitudinal Studies10aMale10aMyocardial Infarction10aNational Heart, Lung, and Blood Institute (U.S.)10aPolymorphism, Single Nucleotide10aProportional Hazards Models10aUnited States1 aShiffman, Dov1 aO'Meara, Ellen, S1 aBare, Lance, A1 aRowland, Charles, M1 aLouie, Judy, Z1 aArellano, Andre, R1 aLumley, Thomas1 aRice, Kenneth1 aIakoubova, Olga1 aLuke, May, M1 aYoung, Bradford, A1 aMalloy, Mary, J1 aKane, John, P1 aEllis, Stephen, G1 aTracy, Russell, P1 aDevlin, James, J1 aPsaty, Bruce, M uhttps://chs-nhlbi.org/node/995