Genome-wide association study identifies five new schizophrenia loci.
Genome-wide association study identifies five new schizophrenia loci.
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我们在一项大规模的全基因组关联研究中研究了常见遗传变异在精神分裂症中的作用：第一阶段的发现样本为21，856名欧洲血统的个体，第二阶段的复制样本为29，839名独立受试者。第1阶段和第2阶段的分析结果显示，7个基因座与精神分裂症有显著的全基因组关联，其中5个是新发现的（1p21.3、2q32.3、8p23.2、8q21.3和10q24.32-q24.33），2个是先前发现的（6p21.32-p22.1和18q21.2）。最强有力的新发现（P = 1.6 × 10−11）是在MIR 137（microRNA 137）的假定初级转录本的内含子中发现了rs 1625579，MIR 137是一种已知的神经元发育调节因子。实现全基因组意义的其他四个精神分裂症位点包含MIR 137的预测靶点，表明MIR 137介导的失调是精神分裂症中以前未知的病因机制。在对双相情感障碍样本（16，374名受影响个体和14，044名对照）的联合分析中，三个位点达到了全基因组显著性：CACNA 1C（rs 4765905，P = 7.0 × 10−9），ANK 3（rs 10994359，P = 2.5 × 10−8）和ITIH 3-ITIH 4区域（rs 2239547，P = 7.8 × 10−9）。
We examined the role of common genetic variation in schizophrenia in a genome-wide association study of substantial size: a stage 1 discovery sample of 21,856 individuals of European ancestry and a stage 2 replication sample of 29,839 independent subjects. The combined stage 1 and 2 analysis yielded genome-wide significant associations with schizophrenia for seven loci, five of which are new (1p21.3, 2q32.3, 8p23.2, 8q21.3 and 10q24.32-q24.33) and two of which have been previously implicated (6p21.32-p22.1 and 18q21.2). The strongest new finding (P = 1.6 × 10−11) was with rs1625579 within an intron of a putative primary transcript for MIR137 (microRNA 137), a known regulator of neuronal development. Four other schizophrenia loci achieving genome-wide significance contain predicted targets of MIR137, suggesting MIR137-mediated dysregulation as a previously unknown etiologic mechanism in schizophrenia. In a joint analysis with a bipolar disorder sample (16,374 affected individuals and 14,044 controls), three loci reached genome-wide significance: CACNA1C (rs4765905, P = 7.0 × 10−9), ANK3 (rs10994359, P = 2.5 × 10−8) and the ITIH3-ITIH4 region (rs2239547, P = 7.8 × 10−9).