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

• Published in: Scientific reports 2016-04, Vol.6 (1), p.24914-24914, Article 24914
• Main Authors: Guan, Fanglin, Zhang, Tianxiao, Liu, Xinshe, Han, Wei, Lin, Huali, Li, Lu, Chen, Gang, Li, Tao
• Format: Article
• Language: English
• Subjects: 631/208/727/2000; 631/208/727/728; 692/699/476/1799; Asian Continental Ancestry Group; Calcium Channels - genetics; DNA, Intergenic; Genetic Association Studies; Genetic Predisposition to Disease; Humanities and Social Sciences; Humans; multidisciplinary; Polymorphism, Single Nucleotide; Schizophrenia - genetics; Science
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep24914

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