Common variants on 2p16.1, 6p22.1 and 10q24.32 are associated with schizophrenia in Han Chinese population
Common variants on 2p16.1, 6p22.1 and 10q24.32 are associated with schizophrenia in Han Chinese population
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2p16.1、6p22.1和10q24.32的常见变异与中国汉族人群的精神分裂症相关
DOI：
10.1038/mp.2016.212
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发表时间：
2017
影响因子：
11
通讯作者：
Yue W
中科院分区：
文献类型：
--
作者：
Yu H;Yan H;Li J;Li Z;Zhang X;Ma Y;Mei L;Liu C;Cai L;Wang Q;Zhang F;Iwata N;Ikeda M;Wang L;Lu T;Li M;Xu H;Wu X;Liu B;Yang J;Li K;Lv L;Ma X;Wang C;Li L;Yang F;Jiang T;Shi Y;Li T;Zhang D;Yue W
通过全基因组关联研究（GWASs）在欧洲人群中发现了许多精神分裂症易感基因座。然而，直到最近，精神分裂症GWAS在非欧洲人群中仅限于小样本量，并产生了一些与精神分裂症相关的基因座。为了确定中国汉族人群中精神分裂症的遗传风险变异，我们对4384例精神分裂症患者和5770名对照者进行了两阶段GWAS，随后在另外4339例精神分裂症患者和7043名中国汉族对照者中进行了13个单核苷酸多态性的独立重复。此外，我们根据发现阶段的结果进行了额外的分析。综合分析证实了中国汉族人群中2p16.1的三个基因座的全基因组显著关联的证据。（rs 1051061，在VRK 2的一个外显子中，P=1.14 × 10-12，OR =1.17），6p22.1（rs 115070292在GABBR 1的内含子中，P=4.96 × 10-10，OR=0.77）和10q24.32（rs 10883795在AS 3 MT内含子中，P=7.94 × 10-10，OR=0.87; rs 10883765在ARL 3内含子中，P=3.06 × 10-9，OR=0.87）。基于精神病基因组学联盟精神分裂症GWAS数据的多基因风险评分适度预测中国人群的病例对照状态（Nagelkerke R2：1.7% ~5.7%）。我们的通路分析表明，神经生物学途径，如GABA能信号，多巴胺能信号，细胞粘附分子和髓鞘形成途径参与精神分裂症。这些发现为中国汉族人群精神分裂症的发病机制提供了新的见解。需要进一步的研究来建立这些发现的生物学背景和潜在的临床应用。
Many schizophrenia susceptibility loci have been identified through genome-wide association studies (GWASs) in European populations. However, until recently, schizophrenia GWASs in non-European populations were limited to small sample sizes and have yielded few loci associated with schizophrenia. To identify genetic risk variations for schizophrenia in the Han Chinese population, we performed a two-stage GWAS of schizophrenia comprising 4384 cases and 5770 controls, followed by independent replications of 13 single-nucleotide polymorphisms in an additional 4339 schizophrenia cases and 7043 controls of Han Chinese ancestry. Furthermore, we conducted additional analyses based on the results in the discovery stage. The combined analysis confirmed evidence of genome-wide significant associations in the Han Chinese population for three loci, at 2p16.1 (rs1051061, in an exon of VRK2, P=1.14 × 10-12, odds ratio (OR)=1.17), 6p22.1 (rs115070292 in an intron of GABBR1, P=4.96 × 10-10, OR=0.77) and 10q24.32 (rs10883795 in an intron of AS3MT, P=7.94 × 10-10, OR=0.87; rs10883765 at an intron of ARL3, P=3.06 × 10-9, OR=0.87). The polygenic risk score based on Psychiatric Genomics Consortium schizophrenia GWAS data modestly predicted case-control status in the Chinese population (Nagelkerke R2: 1.7% ~5.7%). Our pathway analysis suggested that neurological biological pathways such as GABAergic signaling, dopaminergic signaling, cell adhesion molecules and myelination pathways are involved in schizophrenia. These findings provide new insights into the pathogenesis of schizophrenia in the Han Chinese population. Further studies are needed to establish the biological context and potential clinical utility of these findings.