Abstract 1785: Two New Susceptibility Loci for Coronary Artery Disease on Chromosomes 2p24.3 and 10q24.32
Recently, genome-wide association studies (GWAS) identified a total of 12 genes robustly associated with coronary artery disease (CAD) and myocardial infarction (MI). However, these genes explain only a small proportion of the heritability of the disease. The aim was to identify additional CAD/MI loci by conducting a GWAS with subsequent in-silico replication in two independent GWAS data sets for MI (GerMIFS I and GerMIFS II). In stage 1, we genotyped 1,359 MI cases and 1,883 population-based controls (GerMIFS III (KORA)) with the Affymetrix® Genome-Wide Human SNP Array 5.0 and 6.0, respectively. The inflation factor estimated by all genotyped SNPs that passed QC is 1.10. Of these, 384 SNPs showed association with MI at P≤ 1×10 −3 in the two-sided trend test. These SNPs were evaluated by in-silico analysis in the GerMIFS I (875 cases/1644 controls) and GerMIFS II (1222 cases/1298 controls). We identified only 4 SNPs clustering in two regions which show exact replication in both studies. rs6732084 and rs7595264 are located on chromosome 2p24.32 and rs3740390 and rs11191580 on chromosome 10q24.32. The combined p-values for the lead SNPs in both regions are p=9.88 × 10 −9 for rs6732084 and P=1.61 × 10 −7 for rs3740390. Analysis of a GWAS followed by in-silico replication of all SNPs with P≤1×10 −3 in two GWAS data sets identified one new locus for CAD on 2p24.32 with compelling statistical evidence and a second locus on 10q24.32 with suggestive evidence. However, replication steps are needed to further establish the role of these loci in the etiology of CAD/MI.