Evaluation of voltage-dependent calcium channel γ gene families identified several novel potential susceptible genes to schizophrenia.
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), Pperm < 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.
Department of Forensic Psychiatry, School of Medicine &Forensics, Xi'an Jiaotong University, Xi'an, China.|Key Laboratory of National Ministry of Health for Forensic Sciences, School of Medicine &Forensics, Xi'an Jiaotong University, Xi'an, China.
Fanglin
F
Guan
Department of Psychiatry, School of Medicine, Washington University, Saint Louis, MO, USA.
Tianxiao
T
Zhang
Key Laboratory of National Ministry of Health for Forensic Sciences, School of Medicine &Forensics, Xi'an Jiaotong University, Xi'an, China.|Department of Forensic Medicine, School of Medicine &Forensics, Xi'an Jiaotong University, Xi'an, China.
Xinshe
X
Liu
Department of Forensic Psychiatry, School of Medicine &Forensics, Xi'an Jiaotong University, Xi'an, China.|Key Laboratory of National Ministry of Health for Forensic Sciences, School of Medicine &Forensics, Xi'an Jiaotong University, Xi'an, China.
Wei
W
Han
Xi'an Mental Health Center, Xi'an, China.
Huali
H
Lin
Key Laboratory of National Ministry of Health for Forensic Sciences, School of Medicine &Forensics, Xi'an Jiaotong University, Xi'an, China.
Lu
L
Li
Key Laboratory of National Ministry of Health for Forensic Sciences, School of Medicine &Forensics, Xi'an Jiaotong University, Xi'an, China.
Gang
G
Chen
Key Laboratory of National Ministry of Health for Forensic Sciences, School of Medicine &Forensics, Xi'an Jiaotong University, Xi'an, China.|Department of Forensic Medicine, School of Medicine &Forensics, Xi'an Jiaotong University, Xi'an, China.
Tao
T
Li
D044466:Asian People; D015220:Calcium Channels / Q000235:genetics*; D021901:DNA, Intergenic; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000235:genetics*
C521175:CACNG4 protein, human; C521176:CACNG5 protein, human; C521177:CACNG6 protein, human; C521178:CACNG8 protein, human; D015220:Calcium Channels; D021901:DNA, Intergenic