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 compri...

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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
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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
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creator Guan, Fanglin
Zhang, Tianxiao
Liu, Xinshe
Han, Wei
Lin, Huali
Li, Lu
Chen, Gang
Li, Tao
description 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  
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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  &lt; 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. 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Epistasis analyses were conducted and significant statistical interaction (OR = 0.622, P  = 2.93 × 10 −6 , P perm  &lt; 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. 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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
title Evaluation of voltage-dependent calcium channel γ gene families identified several novel potential susceptible genes to schizophrenia
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