全基因组关联分析确定了 13 个精神分裂症的新风险位点。

Genome-wide association analysis identifies 13 new risk loci for schizophrenia.

机构信息

1] Analytical and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts, USA. [2] Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA. [3].

出版信息

Nat Genet. 2013 Oct;45(10):1150-9. doi: 10.1038/ng.2742. Epub 2013 Aug 25.

Abstract

Schizophrenia is an idiopathic mental disorder with a heritable component and a substantial public health impact. We conducted a multi-stage genome-wide association study (GWAS) for schizophrenia beginning with a Swedish national sample (5,001 cases and 6,243 controls) followed by meta-analysis with previous schizophrenia GWAS (8,832 cases and 12,067 controls) and finally by replication of SNPs in 168 genomic regions in independent samples (7,413 cases, 19,762 controls and 581 parent-offspring trios). We identified 22 loci associated at genome-wide significance; 13 of these are new, and 1 was previously implicated in bipolar disorder. Examination of candidate genes at these loci suggests the involvement of neuronal calcium signaling. We estimate that 8,300 independent, mostly common SNPs (95% credible interval of 6,300-10,200 SNPs) contribute to risk for schizophrenia and that these collectively account for at least 32% of the variance in liability. Common genetic variation has an important role in the etiology of schizophrenia, and larger studies will allow more detailed understanding of this disorder.

摘要

精神分裂症是一种特发性精神障碍,具有遗传成分,对公共健康有重大影响。我们进行了一项多阶段全基因组关联研究(GWAS),研究对象为精神分裂症,首先是一个瑞典全国性样本(5001 例病例和 6243 例对照),然后与以前的精神分裂症 GWAS 进行荟萃分析(8832 例病例和 12067 例对照),最后在独立样本中对 168 个基因组区域的 SNPs 进行复制(7413 例病例、19762 例对照和 581 对亲子三系)。我们确定了 22 个与全基因组显著相关的位点;其中 13 个是新的,1 个先前与双相情感障碍有关。对这些位点候选基因的检查表明,神经元钙信号参与其中。我们估计,8300 个独立的、大多数常见的 SNPs(95%可信区间为 6300-10200 SNPs)导致精神分裂症的风险,这些 SNPs 共同至少解释了发病倾向的 32%。常见的遗传变异在精神分裂症的病因学中起着重要作用,更大的研究将使我们能够更详细地了解这种疾病。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e6d9/3827979/5d93b4f77407/nihms512111f1.jpg

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