Stroke and Dementia Research Centre, St Georges University of London, Cranmer Terrace, London, UK.
Hum Mol Genet. 2011 Oct 15;20(R2):R124-31. doi: 10.1093/hmg/ddr345. Epub 2011 Aug 10.
Stroke represents an enormous health problem worldwide. It describes a clinical syndrome which can be caused by a number of different pathologies, rather than a single disease. Over 80% of strokes are ischaemic, as opposed to haemorrhagic. This review covers advances in the genetics of both monogenic and multifactorial ischaemic stroke. Like many other complex diseases, progress in identifying genes for multifactorial stroke has been disappointing. However, genome-wide association study (GWAS) technology is starting to have a major impact on our understanding of the genetics of stroke. Early studies have shown that genetic associations identified with other diseases known to be associated with stroke, such as coronary heart disease and atrial fibrillation, are themselves genetic risk factors for stroke. A number of stroke GWASs are nearing completion; these have identified novel associations with ischaemic stroke. Most associations reported to date are with specific stroke subtypes. This parallels findings from monogenic causes of stroke where individual mutations usually predispose to specific stroke subtypes. This has implications for the understanding of the pathogenesis of stroke, and emphasizes the importance of careful stroke subtyping in genetic epidemiology studies. So far, studies have looked for genetic risk factors for stroke acting independently of environmental factors. However, we know that conventional environmental risk factors are important in stroke pathogenesis, and considerable evidence suggests that gene-environment interactions will be important. Identifying these is likely to require much larger sample sizes.
中风是一个全球性的重大健康问题。它描述了一种可以由多种不同的病理引起的临床综合征，而不是一种单一的疾病。超过 80%的中风是缺血性的，而不是出血性的。本综述涵盖了单基因和多因素缺血性中风的遗传学进展。像许多其他复杂疾病一样，确定多因素中风基因的进展令人失望。然而，全基因组关联研究（GWAS）技术开始对我们理解中风的遗传学产生重大影响。早期研究表明，与其他已知与中风相关的疾病（如冠心病和心房颤动）相关的遗传关联本身就是中风的遗传风险因素。一些中风 GWAS 即将完成；这些研究确定了与缺血性中风的新关联。迄今为止报告的大多数关联都与特定的中风亚型有关。这与中风的单基因病因学的发现相平行，在中风的单基因病因学中，单个突变通常会导致特定的中风亚型。这对中风发病机制的理解具有重要意义，并强调了在遗传流行病学研究中仔细进行中风亚型分类的重要性。到目前为止，研究一直在寻找独立于环境因素的中风遗传风险因素。然而，我们知道传统的环境风险因素在中风发病机制中很重要，而且有大量证据表明基因-环境相互作用将很重要。确定这些因素可能需要更大的样本量。
