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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.
Figures and Tables
Fig. 1
Location of three SNPs on intron 3 in CACNA1C gene. A : Location of the single nucleotide polymorphisms (SNPs) on intron 3 in Calcium voltage-gated channel subunit alpha1C (CACNA1C) gene analyzed in the current study. B : Linkage disequilibrium (LD) structure of three SNPs. The number in each LD indicates the value of D' (D'=1 not shown) calculated from normal control data. Block 1 was determined using the default confidence interval algorithm of Haploview 4.2.
Table 1
Demographic characteristics of the subjects
* : After post-hoc analysis, BD-II group was older than the other groups and the control group was younger than the other groups. More males were in the schizophrenia group than in the BD-I and control groups, and the BD-II group had more females than the other groups. BD-I : Bipolar Disorder-I, BD-II : Bipolar Disorder-II
Table 2
Effects of single nucleotide polymorphisms (SNPs) in CACNA1C gene on schizophrenia and bipolar I and bipolar II disorder
Table 3
Effects of single nucleotide polymorphisms in CACNA1C gene on schizophrenia and bipolar I and bipolar II disorders : Summary results under the best-fit genetic model
* : Nominal P-value of the logistic regression analyses using age and sex as a covariate, †: The inheritance model with the least Akaike Information Criterion was accepted as the best fitting mode, ‡: p-values of <0.05 after Bonferroni correction. SNP : single nucleotide polymorphism, MAF : minor allele frequency based on the control group data, MM : major allele homozygote, Mm : heterozygote, mm : minor allele homozygote, BD : bipolar disorder, BD-I : Bipolar Disorder-I, BD-II : Bipolar Disorder-II : Schizophrenia+BD, group merged with Schizophrenia and Bipolar Disorder groups, Schizophrenia+BD-I : group merged with Schizophrenia and Bipolar Disorder-I groups
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