조현병과 제1형 양극성장애의 진단 경계를 넘어선 공통적 후보유전자로서의CACNA1C 에 대한 단일염기다형성 연합 연구
Association between a Genetic Variant of CACNA1C and the Risk of Schizophrenia and Bipolar I Disorder Across Diagnostic Boundaries
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Objectives : Genome-wide association studies (GWASs) and meta-analyses indicate that single-nucleotide polymorphisms (SNPs) in the a-1C subunit of the L-type voltage-dependent calcium channel (CACNA1C) gene increase the risk for schizophrenia and bipolar disorders (BDs). We investigated the association between the genetic variants on CACNA1C and schizophrenia and/or BDs in the Korean population. Methods : A total of 582 patients with schizophrenia, 336 patients with BDs consisting of 179 bipolar I disorder (BD-I) and 157 bipolar II disorder (BD-II), and 502 healthy controls were recruited. Based on previous results from other populations, three SNPs (rs10848635, rs1006737, and rs4765905) were selected and genotype-wise association was evaluated using logistic regression analysis under additive, dominant and recessive genetic models. Results : rs10848635 showed a significant association with schizophrenia (p=0.010), the combined schizophrenia and BD group (p=0.018), and the combined schizophrenia and BD-I group (p=0.011). The best fit model was dominant model for all of these phenotypes. The association remained significant after correction for multiple testing in schizophrenia and the combined schizophrenia and BD-I group. Conclusion : We identified a possible role of CACNA1C in the common susceptibility of schizophrenia and BD-I. However no association trend was observed for BD-II. Further efforts are needed to identify a specific phenotype associated with this gene crossing the current diagnostic categories.
Abstract
Objectives : Genome-wide association studies (GWASs) and meta-analyses indicate that single-nucleotide polymorphisms (SNPs) in the a-1C subunit of the L-type voltage-dependent calcium channel (CACNA1C) gene increase the risk for schizophrenia and bipolar disorders (BDs). We investigated the association between the genetic variants on CACNA1C and schizophrenia and/or BDs in the Korean population. Methods : A total of 582 patients with schizophrenia, 336 patients with BDs consisting of 179 bipolar I disorder (BD-I) and 157 bipolar II disorder (BD-II), and 502 healthy controls were recruited. Based on previous results from other populations, three SNPs (rs10848635, rs1006737, and rs4765905) were selected and genotype-wise association was evaluated using logistic regression analysis under additive, dominant and recessive genetic models. Results : rs10848635 showed a significant association with schizophrenia (p=0.010), the combined schizophrenia and BD group (p=0.018), and the combined schizophrenia and BD-I group (p=0.011). The best fit model was dominant model for all of these phenotypes. The association remained significant after correction for multiple testing in schizophrenia and the combined schizophrenia and BD-I group. Conclusion : We identified a possible role of CACNA1C in the common susceptibility of schizophrenia and BD-I. However no association trend was observed for BD-II. Further efforts are needed to identify a specific phenotype associated with this gene crossing the current diagnostic categories.
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