@article {995, title = {Association of gene variants with incident myocardial infarction in the Cardiovascular Health Study.}, journal = {Arterioscler Thromb Vasc Biol}, volume = {28}, year = {2008}, month = {2008 Jan}, pages = {173-9}, abstract = {

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.

}, keywords = {African Americans, Aged, Aged, 80 and over, Coronary Disease, European Continental Ancestry Group, Female, Genetic Predisposition to Disease, Humans, Longitudinal Studies, Male, Myocardial Infarction, National Heart, Lung, and Blood Institute (U.S.), Polymorphism, Single Nucleotide, Proportional Hazards Models, United States}, issn = {1524-4636}, doi = {10.1161/ATVBAHA.107.153981}, author = {Shiffman, Dov and O{\textquoteright}Meara, Ellen S and Bare, Lance A and Rowland, Charles M and Louie, Judy Z and Arellano, Andre R and Lumley, Thomas and Rice, Kenneth and Iakoubova, Olga and Luke, May M and Young, Bradford A and Malloy, Mary J and Kane, John P and Ellis, Stephen G and Tracy, Russell P and Devlin, James J and Psaty, Bruce M} } @article {1064, title = {Gene variants associated with ischemic stroke: the cardiovascular health study.}, journal = {Stroke}, volume = {40}, year = {2009}, month = {2009 Feb}, pages = {363-8}, abstract = {

BACKGROUND AND PURPOSE: The purpose of this study was to determine whether 74 single nucleotide polymorphisms (SNPs), which had been associated with coronary heart disease, are associated with incident ischemic stroke.

METHODS: Based on antecedent studies of coronary heart disease, we prespecified the risk allele for each of the 74 SNPs. We used Cox proportional hazards models that adjusted for traditional risk factors to estimate the associations of these SNPs with incident ischemic stroke during 14 years of follow-up in a population-based study of older adults: the Cardiovascular Health Study (CHS).

RESULTS: In white CHS participants, the prespecified risk alleles of 7 of the 74 SNPs (in HPS1, ITGAE, ABCG2, MYH15, FSTL4, CALM1, and BAT2) were nominally associated with increased risk of stroke (one-sided P<0.05, false discovery rate=0.42). In black participants, the prespecified risk alleles of 5 SNPs (in KRT4, LY6G5B, EDG1, DMXL2, and ABCG2) were nominally associated with stroke (one-sided P<0.05, false discovery rate=0.55). The Val12Met SNP in ABCG2 was associated with stroke in both white (hazard ratio, 1.46; 90\% CI, 1.05 to 2.03) and black (hazard ratio, 3.59; 90\% CI, 1.11 to 11.6) participants of CHS. Kaplan-Meier estimates of the 10-year cumulative incidence of stroke were greater among Val allele homozygotes than among Met allele carriers in both white (10\% versus 6\%) and black (12\% versus 3\%) participants of CHS.

CONCLUSIONS: The Val12Met SNP in ABCG2 (encoding a transporter of sterols and xenobiotics) was associated with incident ischemic stroke in white and black participants of CHS.

}, keywords = {African Continental Ancestry Group, Aged, Alleles, Brain Ischemia, Cardiovascular Diseases, Coronary Disease, Ethnic Groups, European Continental Ancestry Group, Female, Gene Frequency, Genetic Variation, Humans, Kaplan-Meier Estimate, Male, Polymorphism, Single Nucleotide, Prospective Studies, Risk Factors, Stroke, United States}, issn = {1524-4628}, doi = {10.1161/STROKEAHA.108.521328}, author = {Luke, May M and O{\textquoteright}Meara, Ellen S and Rowland, Charles M and Shiffman, Dov and Bare, Lance A and Arellano, Andre R and Longstreth, W T and Lumley, Thomas and Rice, Kenneth and Tracy, Russell P and Devlin, James J and Psaty, Bruce M} }