Validation of eight genetic risk factors in East Asian populations replicated the association of BRAP with coronary artery disease.

Coronary artery disease (CAD) is caused by a thrombotic occlusion or spasm of the coronary artery. Association of genetic variants with susceptibility to CAD has been reported in various populations, but the association should be replicated in other populations to establish the role of genetic variants in CAD. We conducted a case-control study with a total of 1480 CAD cases and 2115 controls from two East Asian populations, Japanese and Korean, to validate the associations of CAD with eight single nucleotide polymorphisms (SNPs) in eight loci, which were identified from large-scale whole-genome association studies in Europeans or East Asians. Among the tested SNPs, one SNP in BRAP (rs11066001) showed a significant association in allele frequency distribution with CAD in both the Japanese (Odds ratio (OR)=1.63, 95% confidence interval (CI); 1.41-1.89, P=5.0 x 10(-11), corrected P (Pc)=4.0 x 10(-10)) and Korean populations (OR=1.68, 95% CI; 1.41-2.00, P=6.5 x 10(-9), Pc=5.2 x 10(-9)), and a meta-analysis showed a significant association in the East Asian populations (OR=1.65, 95% CI; 1.48-1.85, P=1.8 x 10(-18), Pc=1.4 x 10(-17)), whereas no evidence of association was found for the other SNPs. In addition, a combined analysis of BRAP and another CAD locus on 9p21 suggested that these loci had a synergistic role in the susceptibility. Failure to replicate the association with the other SNPs, which were reported in the European populations, suggested that their contributions to CAD were not large enough to be readily captured in the East Asian populations.