Abstract
IntroductionSchizophrenia is a serious mental illness with a genetic predisposition. Genome‐wide association studies (GWAS) have identified the α‐1C subunit of the L‐type voltage‐gated calcium channel (CACNA1C) gene as a significant risk gene for schizophrenia. However, there are inconsistent conclusions in case–control studies.MethodsWe performed a comprehensive meta‐analysis of all available samples from existing studies under four different genetic models (recessive model, dominant model, additive model and allele model) to further confirm whether CACNA1C rs1006737 is an authentic risk single nucleotide polymorphism (SNP) for schizophrenia.ResultsA statistically significant difference under the four models (all p < 0.05) was observed by pooling nine Asian and European studies, including a total of 12,744 cases and 16,460 controls. For European‐decent samples, a significant difference was identified between patients and controls for the four models (all p < 0.05). We observed a significant difference between patients and controls for the recessive model and allele model (GG vs. GA + AA: p < 0.00001; G vs. A: p < 0.00001) using a fixed effect model, but the dominant model (GG + GA vs. AA: OR: p = 0.15) and additive model (GG vs. AA: p = 0.11) showed no significant difference between patients and controls in the Asian samples.ConclusionOur findings provide important evidence for the establishment of CACNA1C as a susceptibility gene for schizophrenia across world populations, but its roles in the pathogenesis of schizophrenia need to be further investigated.
Highlights
Schizophrenia is a serious mental illness with a genetic predisposition
According to the neurodevelopmental hypothesis of schizophrenia (Fatemi & Folsom, 2009), any factor that can affect the development of the nervous system may be the cause of schizo‐ phrenia; the CACNA1C gene may be involved in schizophrenia by regulating the development of the nervous system
We observed a significant difference between patients and controls for the recessive model and allele model (GG vs. GA + AA: odds ratio (OR): 0.83, 95% confidence interval (95% CI): 0.77–0.89, p < 0.00001; G vs. A: OR: 0.84, 95% CI: 0. 78–0.90, p < 0.00001) using a fixed effect model but the dominant model (GG + GA vs. AA: OR: 0.78, 95% CI: 0.56– 1.09 p = 0.15) and additive model (GG vs. AA: OR: 0.76, 95% CI: 0.55–1.06, p = 0.11) showed no significant difference between pa‐ tients and controls
Summary
Schizophrenia is a severe psychiatric disease that has a serious ad‐ verse impact on society, families, and patients, affecting approxi‐ mately 1% of the worldwide population (Sukanta, David, Joy, & John, 2005). Based on the potential possibility of shared risk variants in schizo‐ phrenia, studies from Europe reported a significant association of the A‐allele of SNP rs1006737 with schizophrenia in a Danish cohort (Nyegaard et al, 2010), a British cohort (Green et al, 2010), and a Spanish cohort (Ivorra et al, 2014) These results were successfully replicated in some Asian studies (Guan et al, 2014; Guanchen, Zhang, Fuquan, Zhiqiang, & Wei, 2017; Kuanjun et al, 2014; Porcelli et al, 2015; Zheng et al, 2014). We there‐ fore conducted a meta‐analysis integrating nine studies under four different genetic models to evaluate the association of rs1006737 in the CACNA1C gene with schizophrenia
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