Association between a Genetic Variant of CACNA1C and the Risk of Schizophrenia and Bipolar I Disorder Across Diagnostic Boundaries.

Lee, Bora; Baek, Ji Hyun; Cho, Eun Young; Yang, So Yung; Choi, Yoo Jin; Lee, Yu Sang; Ha, Kyooseob; Hong, Kyung Sue

doi:2018.21.2.43

Korean J Schizophr Res > Volume 21(2); 2018 > Article

Original Article

Korean Journal of Schizophrenia Research 2018;21(2):43-50.
DOI: https://doi.org/10.16946/kjsr.2018.21.2.43 Published online October 31, 2018.

Association between a Genetic Variant of CACNA1C and the Risk of Schizophrenia and Bipolar I Disorder Across Diagnostic Boundaries.

Bora Lee, Ji Hyun Baek, Eun Young Cho, So Yung Yang, Yoo Jin Choi, Yu Sang Lee, Kyooseob Ha, Kyung Sue Hong

¹Department of Psychiatry, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Korea. hongks@skku.edu
²Center for Clinical Research, Samsung Biomedical Research Institute, Seoul, Korea.
³St. Andrew's Hospital, Icheon, Korea.
⁴Yong-In Mental Hospital, Yongin, Korea.
⁵Department of Psychiatry, Seoul National University College of Medicine, Seoul, Korea.

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.

Key Words: CACNA1C · Schizophrenia · Bipolar disorder · SNPs · Genetic association study