Evaluating the association between CACNA1C rs1006737 and schizophrenia risk: A meta-analysis

Introduction: Genetic analyses including genome-wide association studies have reported an intronic single nucleotide polymorphism (SNP) rs1006737 in CACNA1C gene (encoded calcium channel, voltage-dependent, L type, alpha 1C subunit) as a risk factor for schizophrenia in European populations. The replications in other ethnic populations such as East Asians have also been conducted, but the results were inconsistent, either likely due to the limited sample size of single study or genetic heterogeneity between continental populations on this locus.

Methods: We performed a comprehensive meta-analysis of all available samples from existing studies of East Asian populations, including a total of 9,432 cases and 10,661 controls, to further confirm whether CACNA1C rs1006737 is an authentic risk SNP for schizophrenia in East Asian populations.

Results: Our results revealed a significant association between rs1006737 and schizophrenia (allelic model, P = 4.39 × 10(-6) , pooled odds ratio [OR] = 1.20), and the results were much strengthened when the European and East Asian samples were combined together (P = 2.40 × 10(-17) , pooled OR = 1.12). There is no significant heterogeneity or publication bias between individual studies, and removal of any single study still remained significant associations between rs1006737 and schizophrenia.

Discussion: Our results further confirmed that rs1006737 should be categorized as an authentic risk SNP for schizophrenia in the general populations.