Evaluation of genetic susceptibility of common variants in CACNA1D with schizophrenia in Han Chinese

Sci Rep. 2015 Aug 10:5:12935. doi: 10.1038/srep12935.

Abstract

The heritability of schizophrenia (SCZ) has been estimated to be as high as 80%, suggesting that genetic factors may play an important role in the etiology of SCZ. Cav1.2 encoded by CACNA1C and Cav1.3 encoded by CACNA1D are dominant calcium channel-forming subunits of L-type Voltage-dependent Ca(2+) channels, expressed in many types of neurons. The CACNA1C has been consistently found to be a risk gene for SCZ, but it is unknown for CACNA1D. To investigate the association of CACNA1D with SCZ, we designed a two-stage case-control study, including a testing set with 1117 cases and 1815 controls and a validation set with 1430 cases and 4295 controls in Han Chinese. A total of selected 97 tag single nucleotide polymorphisms (SNPs) in CACNA1D were genotyped, and single-SNP association, imputation analysis and gender-specific association analyses were performed in the two independent datasets. None was found to associate with SCZ. Further genotype and haplotype association analyses indicated a similar pattern in the two-stage study. Our findings suggested CACNA1D might not be a risk gene for SCZ in Han Chinese population, which add to the current state of knowledge regarding the susceptibility of CACNA1D to SCZ.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Asian People / genetics*
  • Calcium Channels, L-Type / genetics*
  • Case-Control Studies
  • China
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genotype
  • Haplotypes
  • Humans
  • Linkage Disequilibrium
  • Male
  • Middle Aged
  • Odds Ratio
  • Polymorphism, Single Nucleotide
  • Schizophrenia / genetics*
  • Schizophrenia / pathology

Substances

  • CACNA1D protein, human
  • Calcium Channels, L-Type