Confirmation of genomewide association signals in Chinese Han population reveals risk loci for ischemic stroke.

Abstract

The first genomewide association study of ischemic stroke in whites has identified multiple susceptibility loci. We confirmed this study by examining associations with ischemic stroke in a Chinese Han population. Twenty-five common variants were genotyped in a relatively large sample size including 1123 subjects with ischemic stroke cases (thrombosis stroke=716, lacunar infarction=407) and 557 normal control subjects. The association analyses were performed at both single nucleotide polymorphism and haplotype levels. False discovery rate q value method was applied for multiple testing corrections. rs11052413, a intergenic single nucleotide polymorphism, was most significantly associated with ischemic stroke independent of traditional cardiovascular risk factors in additive (OR=1.51, 95% CI=1.19 to 1.92, P=7.4 x 10(-4), q=0.018) and dominant models (OR=1.59, 95% CI=1.20 to 2.08, P=9.2 x 10(-4), q=0.023). In addition, both ZNF650 rs10204475 and intergenic single nucleotide polymorphism rs10486776 were associated with ischemic stroke as well as independent of traditional cardiovascular risk factors in dominant models (OR=1.47, 95% CI=1.12 to 1.96, P=0.005, q=0.040 and OR=1.53, 95% CI=1.15 to 2.02, P=0.003, q=0.036, respectively). No significant results were found in stroke subtype analysis after multiple corrections. Our study confirmed previously reported associations between ischemic stroke and rs11052413, rs10486776, and ZNF 650 rs10204475 in a Chinese Han population. The mechanism whereby the genetic variants exert their effects on ischemic stroke remains to be further elucidated.