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

## TL;DR

This study investigates whether genetic variants in CACNA1D are linked to schizophrenia in Han Chinese but finds no significant association.

## Contribution

The study is the first to evaluate the genetic susceptibility of CACNA1D to schizophrenia in the Han Chinese population.

## Key findings

- No significant association was found between CACNA1D variants and schizophrenia in Han Chinese.
- Genotype and haplotype analyses showed consistent patterns across testing and validation datasets.
- CACNA1D is likely not a risk gene for schizophrenia in this population.

## 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 Ca2+ 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.