title: Further evidence for genetic association of CACNA1C and schizophrenia: new risk loci in a Han Chinese population and a meta-analysis.
abstract: CACNA1C (12p13.3) has been implicated as a susceptibility gene for schizophrenia by several replicated genome wide association studies. While these results have been consistent among studies in European populations, the findings in East Asian populations have varied. To test whether CACNA1C is a risk gene for schizophrenia, we conducted a case-control study in 5897 schizophrenic patients and 6323 healthy control subjects selected from Han Chinese population. Our study replicated the positive associations of rs1006737 (P=0.0108, OR=1.16, 95% CI: 1.03-1.29) and rs1024582 (P=0.0062, OR=1.18, 95% CI: 1.05-1.33), and identified a novel risk locus, rs2007044 (P=0.0053, OR=1.08, 95% CI: 1.02-1.14). A meta-analysis of rs1006737 combining our study and previous studies was conducted in a total of 8222 schizophrenia cases and 24,661 healthy controls. In the meta-analysis, the association between rs1006737 and schizophrenia remained significant (OR=1.14, 95% CI: 1.07-1.22, P=0.0001). Stratified analysis showed no heterogeneity between East Asian and European ancestries (χ(2)[1]=0.07, P=0.795), and the difference in pooled ORs between ancestries was not significant (Z=0.25, P=0.801). Our results provide further support for associations of rs1006737 and rs1024582 with schizophrenia, identify a new risk locus rs2007044 in a Han Chinese population, and further establish CACNA1C as an important susceptibility gene for the disease across world populations.
authors.affiliation: Institute of Mental Health, Peking University, Beijing 100191, China; Key Laboratory of Mental Health, Ministry of Health, Peking University, Beijing 100191, China.
authors.forename: Fanfan
authors.initials: F
authors.lastname: Zheng
authors.affiliation: Institute of Mental Health, Peking University, Beijing 100191, China; Key Laboratory of Mental Health, Ministry of Health, Peking University, Beijing 100191, China; Department of Nephrology, Beijing Aerospace General Hospital, Beijing 100076, China.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Epidemiology, Capital Medical University Affiliated Beijing Anzhen Hospital, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, China.
authors.forename: Wuxiang
authors.initials: W
authors.lastname: Xie
authors.affiliation: Department of Psychiatry of the Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453002, China; Henan Mental Hospital, Henan Key Lab of Biological Psychiatry, Xinxiang, Henan 453002, China.
authors.forename: Wenqiang
authors.initials: W
authors.lastname: Li
authors.affiliation: Jinzhou Kangning Hospital, Jinzhou, Liaoning 121013, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Jin
authors.affiliation: Institute of Mental Health, Peking University, Beijing 100191, China; Key Laboratory of Mental Health, Ministry of Health, Peking University, Beijing 100191, China.
authors.forename: Weifeng
authors.initials: W
authors.lastname: Mi
authors.affiliation: Institute of Mental Health, Peking University, Beijing 100191, China; Key Laboratory of Mental Health, Ministry of Health, Peking University, Beijing 100191, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: Jinzhou Kangning Hospital, Jinzhou, Liaoning 121013, China.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Ma
authors.affiliation: Jinzhou Kangning Hospital, Jinzhou, Liaoning 121013, China.
authors.forename: Cuicui
authors.initials: C
authors.lastname: Ma
authors.affiliation: Department of Psychiatry of the Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453002, China; Henan Mental Hospital, Henan Key Lab of Biological Psychiatry, Xinxiang, Henan 453002, China.
authors.forename: Yongfeng
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Hebei Mental Health Center, Baoding, Hebei 071000, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Du
authors.affiliation: Hebei Mental Health Center, Baoding, Hebei 071000, China.
authors.forename: Keqing
authors.initials: K
authors.lastname: Li
authors.affiliation: Institute of Mental Health, Peking University, Beijing 100191, China; Key Laboratory of Mental Health, Ministry of Health, Peking University, Beijing 100191, China.
authors.forename: Chenxing
authors.initials: C
authors.lastname: Liu
authors.affiliation: Institute of Mental Health, Peking University, Beijing 100191, China; Key Laboratory of Mental Health, Ministry of Health, Peking University, Beijing 100191, China.
authors.forename: Lifang
authors.initials: L
authors.lastname: Wang
authors.affiliation: Institute of Mental Health, Peking University, Beijing 100191, China; Key Laboratory of Mental Health, Ministry of Health, Peking University, Beijing 100191, China.
authors.forename: Tianlan
authors.initials: T
authors.lastname: Lu
authors.affiliation: Institute of Mental Health, Peking University, Beijing 100191, China; Key Laboratory of Mental Health, Ministry of Health, Peking University, Beijing 100191, China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Neuroscience Research Institute and Department of Neurobiology, The Key Laboratory for Neuroscience of the Ministry of Education and Health, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: National Institute on Drug Dependence, Peking University, Beijing 100191, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Lu
authors.affiliation: Department of Psychiatry of the Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453002, China; Henan Mental Hospital, Henan Key Lab of Biological Psychiatry, Xinxiang, Henan 453002, China.
authors.forename: Luxian
authors.initials: L
authors.lastname: Lv
authors.affiliation: Institute of Mental Health, Peking University, Beijing 100191, China; Key Laboratory of Mental Health, Ministry of Health, Peking University, Beijing 100191, China; Peking-Tsinghua Center for Life Sciences, Beijing 100871, China; PKU-IDG/McGoven Institute for Brain Research, Peking University, Beijing 100871, China.
authors.forename: Dai
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Institute of Mental Health, Peking University, Beijing 100191, China; Key Laboratory of Mental Health, Ministry of Health, Peking University, Beijing 100191, China. Electronic address: dryue@bjmu.edu.cn.
authors.forename: Weihua
authors.initials: W
authors.lastname: Yue
mesh_terms: D000328:Adult; D044466:Asian People / Q000208:ethnology / Q000235:genetics; D020746:Calcium Channels, L-Type / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011569:Psychiatric Status Rating Scales; D012307:Risk Factors; D012559:Schizophrenia / Q000208:ethnology / Q000235:genetics*; D055815:Young Adult
chemical_list: C079146:CACNA1C protein, human; D020746:Calcium Channels, L-Type
keywords: CACNA1C; Case–control study; Genetic association; Meta-analysis; Schizophrenia; rs1006737