Rao Shuquan, Yao Yao, Zheng Chuan, Ryan Joanne, Mao Canquan, Zhang Fuquan, Meyre David, Xu Qi
School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, China.
Department of Fundamental Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Am J Med Genet B Neuropsychiatr Genet. 2016 Sep;171(6):896-903. doi: 10.1002/ajmg.b.32466. Epub 2016 Jun 3.
Major depressive disorder (MDD) is one of the most common psychiatric disorders with a relatively high heritability (35-40%). Though rs1006737 in the CACNA1C gene showed significant association with MDD in a British large-scale candidate association study, most of the replication analyses with relatively small sample size reported negative association. Moreover, this locus has never been identified in previous genome-wide association studies (GWAS) for MDD. Here, we conducted a comprehensive meta-analysis of the association between CACNA1C variants and MDD risk by combining all published data. Genetic data from one European GWAS and five individual follow-up studies, which include up to 12,629 patients of MDD and 28,653 controls, that is, the largest sample size on CACNA1C to date, were collected. Rs1006737 showed significant association with MDD in the fixed-effect model (Z = 2.56, P = 0.011, OR = 1.08, 95%CI = 1.04-1.12) and the association remained after reanalyzing the data according to ethnicity. We additionally analyzed other 25 SNPs, genotyped in only one replication study, across the CACNA1C locus, and found that two SNPs, rs4765905 (P = 0.041, OR = 1.05, 95%CI 1.00-1.09) and rs4765937 (P = 0.025, OR = 1.05, 95%CI 1.01-1.09) showed nominal association with MDD, while rs2239073 (P = 0.002, OR = 1.07, 95%CI 1.02-1.11) exhibited significant association with MDD, which survived from multiple corrections. Our study provides support for positive association between CACNA1C and MDD; however, the current data suggest the necessity of replication analyses in a larger-scale sample. © 2016 Wiley Periodicals, Inc.
重度抑郁症（MDD）是最常见的精神疾病之一，具有较高的遗传度（35%-40%）。尽管在一项英国大规模候选基因关联研究中，CACNA1C基因中的rs1006737与MDD存在显著关联，但大多数样本量相对较小的重复分析报告的是负相关。此外，在之前针对MDD的全基因组关联研究（GWAS）中，该位点从未被识别出来。在此，我们通过整合所有已发表的数据，对CACNA1C基因变异与MDD风险之间的关联进行了全面的荟萃分析。收集了来自一项欧洲GWAS和五项个体随访研究的基因数据，这些研究共纳入了多达12629例MDD患者和28653例对照，这是迄今为止关于CACNA1C的最大样本量。在固定效应模型中，rs1006737与MDD存在显著关联（Z = 2.56，P = 0.011，OR = 1.08，95%CI = 1.04-1.12），并且在根据种族重新分析数据后，该关联依然存在。我们还分析了仅在一项重复研究中进行基因分型的位于CACNA1C基因座上的其他25个单核苷酸多态性（SNP），发现两个SNP，rs4765905（P = 0.041，OR = 1.05，9%CI 1.00-1.09）和rs4765937（P = 0.025，OR = 1.05，95%CI 1.01-1.09）与MDD存在名义上的关联，而rs2239073（P = 0.002，OR = 1.07，95%CI 1.02-1.11）与MDD存在显著关联，且该关联在多次校正后仍然显著。我们的研究为CACNA1C与MDD之间的正相关提供了支持；然而，目前的数据表明有必要在更大规模的样本中进行重复分析。© 2016威利期刊公司
