Purcell Shaun M, Wray Naomi R, Stone Jennifer L, Visscher Peter M, O'Donovan Michael C, Sullivan Patrick F, Sklar Pamela
Nature. 2009 Aug 6;460(7256):748-52. doi: 10.1038/nature08185. Epub 2009 Jul 1.
Schizophrenia is a severe mental disorder with a lifetime risk of about 1%, characterized by hallucinations, delusions and cognitive deficits, with heritability estimated at up to 80%. We performed a genome-wide association study of 3,322 European individuals with schizophrenia and 3,587 controls. Here we show, using two analytic approaches, the extent to which common genetic variation underlies the risk of schizophrenia. First, we implicate the major histocompatibility complex. Second, we provide molecular genetic evidence for a substantial polygenic component to the risk of schizophrenia involving thousands of common alleles of very small effect. We show that this component also contributes to the risk of bipolar disorder, but not to several non-psychiatric diseases.
精神分裂症是一种严重的精神障碍,终生患病风险约为1%,其特征为幻觉、妄想和认知缺陷,遗传度估计高达80%。我们对3322名患有精神分裂症的欧洲个体和3587名对照进行了全基因组关联研究。在此我们使用两种分析方法展示了常见基因变异在精神分裂症风险中所起作用的程度。首先,我们发现主要组织相容性复合体与之相关。其次,我们提供了分子遗传学证据,表明精神分裂症风险存在大量多基因成分,涉及数千个效应极小的常见等位基因。我们表明这一成分也会导致双相情感障碍的风险增加,但不会导致几种非精神疾病的风险增加。