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

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.

Common variants of HTR1A and SLC6A4 confer the increasing risk of Schizophrenia susceptibility: A population‐based association and epistasis analysis

“…Based on early twin studies, SZ heritability was estimated to range from 60–80% [Cardno and Gottesman, ]. Follow‐up genetic epidemiology research focused on association mapping and identified several genes of interest SZ [Lichtenstein et al, ; Wan et al, ; Guan et al, ; Guan et al, , ; Chen et al, ]. Identifying potential genes has been accelerated with the use of genome‐wide association study (GWAS) designs [SZ Psychiatric GWAS Consortium, ; Ripke et al, ].…”

Evaluation of the Relationship Between Common Variants in the TLR-9 Gene and Hip Osteoarthritis Susceptibility

“…The difference may be due to the different phenotypes of OA (KOA and HOA) or the genetic heterogeneity of different ethnic populations (Liu et al, 2013). Although it is difficult to draw convincing conclusions only from SNP-based association analysis (Yang et al, 2013;Chen et al, 2015;Guan et al, 2015Guan et al, , 2016dZhang et al, 2015Zhang et al, , 2018bJia et al, 2016;Han et al, 2018), further haplotype association analyses confirmed the similar association pattern. These positive results indicated that rs187084 in the TLR-9 gene is associated with both KOA and HOA in the Han Chinese population, which suggests that TLR-9 may play an essential role in the etiology of OA.…”

Transcriptional regulation of voltage‐gated Ca2+ channels

“…Interestingly, these findings might have potential implications for neuropsychiatric diseases, because recent genomewide association studies have identified CACNA1C as a candidate gene in bipolar disorder, schizophrenia, autism and Parkinson's disease . In this context, different genetic studies have also suggested a contribution of Ca V 1.3 channels to neurodegenerative mechanisms associated with schizophrenia and autism …”

“…[36][37][38][39][40] In this context, different genetic studies have also suggested a contribution of Ca V 1.3 channels to neurodegenerative mechanisms associated with schizophrenia and autism. 36,41,42 Ca V 2 channel transcriptional regulation High voltage-activated channels of the Ca V 2 class regulate Ca 2+ entry into nerve cells and thereby contribute to regulate diverse physiological events in the nervous system including membrane excitability, gene expression, neurotransmitter release and synaptic plasticity. As mentioned earlier, four types of Ca V 2 channels (named N, P, Q and R) have been identified based on their physiological and pharmacological properties.…”