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

BACKGROUND AND PURPOSE: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. METHODS: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. RESULTS: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. CONCLUSIONS: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.

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