Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia.
Nat Genet. 2012 Oct;44(10):1147-51. doi: 10.1038/ng.2397. Epub 2012 Sep 2.
Genome-wide association studies (GWAS) have not consistently detected replicable genetic risk factors for ischemic stroke, potentially due to etiological heterogeneity of this trait. We performed GWAS of ischemic stroke and a major ischemic stroke subtype (large artery atherosclerosis, LAA) using 1,162 ischemic stroke cases (including 421 LAA cases) and 1,244 population controls from Australia. Evidence for a genetic influence on ischemic stroke risk was detected, but this influence was higher and more significant for the LAA subtype. We identified a new LAA susceptibility locus on chromosome 6p21.1 (rs556621: odds ratio (OR)=1.62, P=3.9×10(-8)) and replicated this association in 1,715 LAA cases and 52,695 population controls from 10 independent population cohorts (meta-analysis replication OR=1.15, P=3.9×10(-4); discovery and replication combined OR=1.21, P=4.7×10(-8)). This study identifies a genetic risk locus for LAA and shows how analyzing etiological subtypes may better identify genetic risk alleles for ischemic stroke.
全基因组关联研究（GWAS）并未一致检测到可复制的缺血性中风遗传风险因素，这可能是由于该特征的病因异质性。我们使用来自澳大利亚的 1162 例缺血性中风病例（包括 421 例大动脉粥样硬化性中风病例）和 1244 名人群对照进行了缺血性中风和主要缺血性中风亚型（大动脉粥样硬化性，LAA）的 GWAS。证据表明遗传对缺血性中风风险有影响，但这种影响在 LAA 亚型中更高且更显著。我们在 6 号染色体 6p21.1 上确定了一个新的 LAA 易感位点（rs556621：比值比（OR）=1.62，P=3.9×10(-8)），并在来自 10 个独立人群队列的 1715 例 LAA 病例和 52695 例人群对照中复制了这种关联（meta 分析复制 OR=1.15，P=3.9×10(-4)；发现和复制联合 OR=1.21，P=4.7×10(-8)）。这项研究确定了 LAA 的遗传风险位点，并展示了如何分析病因亚型可以更好地识别缺血性中风的遗传风险等位基因。
