Wellcome Trust Centre for Human Genetics, University of Oxford, UK.
Nat Genet. 2012 Feb 5;44(3):328-33. doi: 10.1038/ng.1081.
Genetic factors have been implicated in stroke risk, but few replicated associations have been reported. We conducted a genome-wide association study (GWAS) for ischemic stroke and its subtypes in 3,548 affected individuals and 5,972 controls, all of European ancestry. Replication of potential signals was performed in 5,859 affected individuals and 6,281 controls. We replicated previous associations for cardioembolic stroke near PITX2 and ZFHX3 and for large vessel stroke at a 9p21 locus. We identified a new association for large vessel stroke within HDAC9 (encoding histone deacetylase 9) on chromosome 7p21.1 (including further replication in an additional 735 affected individuals and 28,583 controls) (rs11984041; combined P = 1.87 × 10(-11); odds ratio (OR) = 1.42, 95% confidence interval (CI) = 1.28-1.57). All four loci exhibited evidence for heterogeneity of effect across the stroke subtypes, with some and possibly all affecting risk for only one subtype. This suggests distinct genetic architectures for different stroke subtypes.
遗传因素与中风风险有关，但报道的复制相关性很少。我们对 3548 名中风患者和 5972 名对照者（均为欧洲血统）进行了全基因组关联研究（GWAS），以研究缺血性中风及其亚型。在 5859 名中风患者和 6281 名对照者中进行了潜在信号的复制。我们复制了 PITX2 和 ZFHX3 附近与心源性栓塞性中风以及 9p21 位置与大血管性中风有关的先前关联。我们在 7p21.1 染色体上的 HDAC9（编码组蛋白去乙酰化酶 9）内鉴定出一个与大血管性中风有关的新关联（包括在另外的 735 名中风患者和 28583 名对照者中进一步复制）（rs11984041；合并 P = 1.87×10(-11)；比值比（OR）= 1.42，95%置信区间（CI）= 1.28-1.57）。所有四个位点都表明中风亚型之间存在效应异质性的证据，其中一些甚至可能所有都仅影响一种亚型的风险。这表明不同的中风亚型具有不同的遗传结构。
