Abstract 17557: Genetic Variants Primarily Associated eith Type 2 Diabetes Also Affect Coronary Artery Disease Risk
Multiple single nucleotide polymorphisms (SNPs) have been identified to associate with type 2 diabetes (T2DM). If T2DM is a causal risk factor for coronary artery disease (CAD), SNPs increasing T2DM risk should also increase CAD risk. We studied 38 common genetic variants previously associated with T2DM at a genomewide significant level (plt5x10-8) in CARDIoGRAM, a genomewide data set including 22,233 CAD cases and 64,762 controls. Two SNPs (rs4457053 (ZBED3), rs5945326 (DUSP9)) were excluded because of bad genotyping quality in CARDIoGRAM and no proxy SNP in linkage disequilibrium (r²gt0.8 within 500 bp). For 2 further SNPs pleiotropic effects on other cardiovascular risk factors (lipid traits) have been described by GWAS. These two SNPs (KLF14 (rs972283) and GCKR (rs780094) were also excluded from further analysis. Thus, 34 T2DM-SNPs were tested for association with CAD. Overall, nine T2DM SNPs were nominally significantly (plt0.05) associated with CAD in CARDIoGRAM, a proportion much higher than expected by chance (p=3.3*10-5). Adjusting for the number of SNPs tested (Bonferroni), 1 SNP achieved study-wide significant association with CAD (rs2943651, LOC64673/IRS1, p=3.4*10-5, OR=1.11). The average increase in CAD risk observed per individual T2DM risk allele was 1.08% (95% confidence interval (CI), 0.34-1.83%). Studying a weighted genetic risk score in a subgroup of 4030 cases and 5826 controls revealed that individuals in the top quintile of the T2DM risk score had a 14 % higher risk (CI 5-29 %) of CAD as compared to individuals in the bottom quintile of this score. We performed a second risk score analysis based on summary statistic data from the entire CARDIoGRAM data base. The respective associations with CAD in this by far larger sample were consistent with the analysis of individual data: the p-value for this second risk score was 1.0 * 10-4 confirming a significant association between T2DM SNPs and CAD.Our data indicate that multiple genetic variants associated with T2DM confer a small risk increase for CAD, strengthening the evidence that T2DM is a causal risk factor for CAD.
- © 2012 by American Heart Association, Inc.