Association of CACNA1C polymorphisms (rs1006737, rs4765905, rs2007044) with schizophrenia: A meta-analysis and trial sequential analysis

Schizophrenia is a complex neurological disorder characterized by significant impairment in the perception of reality and changes in behavior. Genetic and environmental factors influence the development of schizophrenia. CACNA1C, which encodes a subunit of a voltage-dependent calcium channel, has been associated with various neurological disorders, including schizophrenia. Several studies have been performed in different populations to explore the association of common genetic variants in the CACNA1C gene with susceptibility to the development of schizophrenia, but results remain contradictory. To draw a definitive conclusion on the association between CACNA1C polymorphisms and schizophrenia, we conducted a meta-analysis focusing on three commonly studied polymorphisms: rs1006737, rs4765905, and rs2007044. For the meta-analysis, a comprehensive literature search was performed using PubMed, Scopus, Science Direct and Google Scholar databases. Data was retrieved, and the meta-analysis was performed using CMA v4 software. The meta-analysis revealed a significant association between rs1006737 and rs2007044 and schizophrenia in the overall population, while no such association was found for rs4765905. Population-wise analysis suggested that all three polymorphisms were significantly associated with schizophrenia in the Asian population and that rs1006737 was significantly associated with schizophrenia in Europeans. We also performed a Trial Sequential Analysis (TSA), which supported our findings. Some report-based assay studies have suggested a role for these polymorphisms in schizophrenia, but further case-control studies are needed to confirm the association of rs4765905 and rs2007044 with the disorder.