导读：作为成人慢性致死疾病的一种重要病因，中风逐渐成为全球关注的公共健康问题。研究者Hugh Markus和同事使用全基因组关联分析手段发现，中风的易感性与若干遗传变异有关。
3月8日，国际著名杂志Nature Genetics在线刊登了德国、英国等国家研究人员的最新研究成果“Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke”，在这篇研究报告中，研究者揭示了中风的易感性与若干遗传变异有关。
作为成人慢性致死疾病的一种重要病因，中风逐渐成为全球关注的公共健康问题。世界上约有80%的中风属于缺血性中风——因血液供应不畅所致。其中，缺血性中风又包含三种常见子类型：大血管中风、心因性脑梗塞中风和小血管中风。
研究者Hugh Markus和同事使用全基因组关联分析手段，对具有欧洲血统的3548例缺血性中风病患以及5972例对照组进行研究，并通过临床评估，脑部和血管成像方法将患者进行子类型分类，他们鉴别出了一个与大血管中风有关的基因区域，其中包括一个名为HDAC9的基因，该基因可对组蛋白去乙酰化酶蛋白进行编码。同时，研究小组还复制出了三个已报道过的相关基因区域，他们发现这四个基因区域在中风的子类型中表现出异质性，这意味着中风子类型的发病机制并不相同。
Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke
Céline Bellenguez, Steve Bevan, Andreas Gschwendtner, Chris C A Spencer, Annette I Burgess, Matti Pirinen, Caroline A Jackson, Matthew Traylor, Amy Strange, Zhan Su, Gavin Band, Paul D Syme, Rainer Malik, Joanna Pera, Bo Norrving, Robin Lemmens et al.
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 nearPITX2 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; combinedP = 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.
文献链接：https://www.nature.com/ng/journal/v44/n3/full/ng.1081.html
