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Voltage-gated L-type calcium channels (VLCC) are distributed widely throughout the brain. Among the genes involved in schizophrenia (SCZ), genes encoding VLCC subunits have attracted widespread attention. Among the four subunits comprising the VLCC (α − 1, α −2/δ, β, and γ), the γ subunit that comprises an eight-member protein family is the least well understood. In our study, to further investigate the risk susceptibility by the γ subunit gene family to SCZ, we conducted a large-scale association study in Han Chinese individuals. The SNP rs17645023 located in the intergenic region of  CACNG4  and  CACNG5  was identified to be significantly associated with SCZ (OR = 0.856,  P  = 5.43 × 10 −5 ). Similar results were obtained in the meta-analysis with the current SCZ PGC data (OR = 0.8853). We also identified a two-SNP haplotype (rs10420331-rs11084307, P = 1.4 × 10 −6 ) covering the intronic region of  CACNG8  to be significantly associated with SCZ. Epistasis analyses were conducted, and significant statistical interaction (OR = 0.622,  P  = 2.93 × 10 −6 ,  P  perm  < 0.001) was observed between rs192808 ( CACNG6 ) and rs2048137 ( CACNG5 ). Our results indicate that  CACNG4 ,  CACNG5 ,  CACNG6  and  CACNG8  may contribute to the risk of SCZ. The statistical epistasis identified between  CACNG5  and  CACNG6  suggests that there may be an underlying biological interaction between the two genes.

Evaluation of voltage-dependent calcium channel γ gene families identified several novel potential susceptible genes to schizophrenia