Association of the CACNA2D2 Gene with Schizophrenia in Chinese Han Population

Background: Schizophrenia (SCZ) is a severely complex psychiatric disorder in which ~80% can be explained by genetic factors. Single nucleotide polymorphisms (SNPs) in calcium channel genes are potential genetic risk factors for a spectrum of psychiatric disorders including SCZ. This study evaluated the association between SNPs in the voltage-gated calcium channel auxiliary subunit alpha2delta 2 gene () and SCZ in the Han Chinese population of Northeast China.

Methods: A total of 761 SCZ patients and 775 healthy controls were involved in this case-control study. Three SNPs (rs3806706, rs45536634 and rs12496815) of were genotyped by the MALDI-TOF-MS technology. Genotype distribution and allele frequency differences between cases and controls were tested by Chi-square (χ ) in males and females respectively using SPSS 24.0 software. Linkage disequilibrium and haplotype analyses were conducted using Haploview4.2. The false discovery rate correction was utilized to control for Type I error by R3.2.3.

Results: There was a significant difference in allele frequencies (χ = 9.545, = 0.006) and genotype distributions (χ = 9.275, = 0.006) of rs45536634 between female SCZ patients and female healthy controls after adjusting for multiple comparisons. Minor allele A (OR = 1.871, 95% CI [1.251-2.798]) and genotype GA + AA (OR = 1.931, 95% CI [1.259-2.963]) were associated with an increased risk of SCZ. Subjects with haplotype AG consisting of rs45536634 and rs12496815 alleles had a higher risk of SCZ (OR = 1.91, 95% CI [1.26-2.90]) compared those with other haplotypes.

Conclusions: This study provides evidence that polymorphisms may influence the susceptibility to SCZ in Han Chinese women.