Liu Weiqing, Liu Fang, Xu Xiufeng, Bai Yan
Department of Psychiatry, the First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, PR China.
Department of Psychiatry, the First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, PR China.
Neurosci Lett. 2017 Apr 24;647:122-128. doi: 10.1016/j.neulet.2017.03.039. Epub 2017 Mar 24.
Schizophrenia is one of the most severe mental disorders with significant heritability. Recent genetic association studies including genome-wide association studies (GWAS) have identified multiple common variants conferring risk of schizophrenia. An intronic SNP within CSMD1, rs10503253, is one of the top risk SNPs for schizophrenia in Europeans discovered through large GWAS. However, whether rs10503253 is also a risk SNP for schizophrenia in other populations, such as Asians, is still unknown. To answer this question, we examined the association of rs10503253 with schizophrenia in a total of 7514 schizophrenia patients, 9058 healthy controls and 1115 nuclear families originated from Asia using a meta-analytic approach. In the meta-analysis of all the samples, we confirmed the association of rs10503253 A-allele with schizophrenia in Asian population (P-value=0.0093, odds ratio=1.062, 95% confidence interval=1.015-1.111), and no genetic heterogeneity between individual samples (P=0.810) was observed. Using the "Leave-one-out" sensitivity analysis, we further confirmed the association between rs10503253 and schizophrenia. These data show that rs10503253 is likely a common schizophrenia risk variant in multiple ethnic groups, and further studies regarding the underlying molecular mechanisms are needed.
精神分裂症是最严重的精神障碍之一，具有显著的遗传力。最近包括全基因组关联研究（GWAS）在内的遗传关联研究已经确定了多个导致精神分裂症风险的常见变异。CSMD1基因内的一个内含子单核苷酸多态性（SNP），即rs10503253，是通过大型GWAS在欧洲人中发现的精神分裂症的顶级风险SNP之一。然而，rs10503253在其他人群（如亚洲人）中是否也是精神分裂症的风险SNP仍不清楚。为了回答这个问题，我们采用荟萃分析方法，在总共7514名精神分裂症患者、9058名健康对照和1115个来自亚洲的核心家庭中，研究了rs10503253与精神分裂症的关联。在对所有样本的荟萃分析中，我们证实了rs10503253 A等位基因与亚洲人群精神分裂症的关联（P值=0.0093，优势比=1.062，95%置信区间=1.015-1.111），并且在各个样本之间未观察到遗传异质性（P=0.810）。使用“留一法”敏感性分析，我们进一步证实了rs10503253与精神分裂症之间的关联。这些数据表明，rs10503253可能是多个种族中常见的精神分裂症风险变异，需要进一步研究其潜在的分子机制。
