精神分裂症病因的探索新发现

报道：《Nature》2014年7月24日——精神疾病基因组学联盟精神分裂症工作组对接近4万个病例进行了一项多阶段精神分裂症全基因组关联研究，多个研究发现可能为精神分裂症病因提供全新见解。这篇文章刊登在最新一期《Nature》杂志上。

中文翻译

【题目】从108个与精神分裂症相关的遗传位点得到的生物学见解

【译文】

精神分裂症是高度遗传性疾病。很多等位基因会带来精神分裂症的遗传风险，包括能够用全基因组关联研究检测出来的常见的、只有小效应的等位基因。 在此我们报道一项多阶段精神分裂症全基因组关联研究，涉及36,989个病例 和 113,075个对照。我们进行了128个独立的关联鉴定，横跨108个保守定义的位点，并且均达到了全基因组显著水平，其中83个以前从未被报道过。在脑中表达的基因之间的关联性被加强，这为研究发现提供了生物学依据。多个研究发现可能为精神分裂症的病因提供全新的见解，DRD2与多个涉及谷氨酸能神经传递的基因的关联性突出了已知分子和精神分裂症治疗之间可能的关联性，并且与精神分裂症的主要病理生理学理论相符。在免疫中起重要作用并且在组织中表达的基因，它们之间的关联性被加强，并且这种关联性的加强不依赖于脑中表达的基因，这为免疫系统和精神分裂症之间存在联系的推测提供了支持。

英文原稿

[Title] Biological insights from 108 schizophrenia-associated genetic loci

[Author] Schizophrenia Working Group of the Psychiatric Genomics Consortium

[Abstract] 

Schizophrenia is a highly heritable disorder. Genetic risk is conferred by a large number of alleles, including common alleles of small effect that might be

detected by genome-wide association studies. Here we report a multi-stage schizophrenia genome-wide association study of up to 36,989 cases and 

113,075 controls. We identify 128 independent associations spanning 108 conservatively defined loci that meet genome-wide significance, 83 of which 

have not been previously reported. Associations were enriched among genes expressed in brain, providing biological plausibility for the findings. Many 

findings have the potential to provide entirely new insights into aetiology, but associations at DRD2 and several genes involved in glutamatergic 

neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological 

hypotheses. Independent of genes expressed in brain, associations were enriched among genes expressed in tissues that have important roles in immunity, 

providing support for the speculated link between the immune system and schizophrenia.

原文地址

http://www.nature.com/nature/journal/v511/n7510/full/nature13595.html