Dataset Information

Association of the CACNA2D2 gene with schizophrenia in Chinese Han population.

ABSTRACT: 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 (CACNA2D2) 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 CACNA2D2 were genotyped by the MALDI-TOF-MS technology. Genotype distribution and allele frequency differences between cases and controls were tested by Chi-square (? 2 ) 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 (? 2 = 9.545, P adj = 0.006) and genotype distributions (? 2 = 9.275, P adj = 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 CACNA2D2 polymorphisms may influence the susceptibility to SCZ in Han Chinese women.

SUBMITTER: Fu Y

PROVIDER: S-EPMC7007731 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Association of the CACNA2D2 gene with schizophrenia in Chinese Han population.

Fu Yingli Y Zhou Na N Bai Wei W Sun Yaoyao Y Chen Xin X Wang Yueying Y Zhang Mingyuan M Kou Changgui C Yu Yaqin Y Yu Qiong Q

PeerJ 20200205

<h4>Background</h4>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 (<i>CACNA2D2</i>) and SCZ in the Han Chinese population of Northeast China.<h4>Methods</h ...[more]

PMID: 32071821

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Project description:ObjectivesSchizophrenia (SZ) is a complex psychiatric disorder with high heritability, and genetic components are thought to be pivotal risk factors for this illness. The glutamate decarboxylase 1 gene (GAD1) was hypothesized to be a candidate risk locus for SZ given its crucial role in the GABAergic neurotransmission system, and previous studies have examined the associations of single nucleotide polymorphisms (SNPs) spanning the GAD1 gene with SZ. However, inconsistent results were obtained. We hence examined the associations between GAD1 SNPs and SZ in two independent case-control samples of Han Chinese ancestry.Materials and methodsTwo Han Chinese SZ case-control samples, referred as the discovery sample and the replication sample, respectively, were recruited for the current study. The discovery sample comprised of 528 paranoid SZ cases (with age of first onset ≥ 18) and 528 healthy controls; the independent replication sample contained 1,256 early onset SZ cases (with age of first onset < 18) and 2,661 healthy controls. Logistic regression analysis was performed to examine the associations between GAD1 SNPs and SZ.ResultsTen SNPs covering GAD1 gene were analyzed in the discovery sample, and two SNPs showed nominal associations with SZ (rs2241165, P = 0.0181, OR = 1.261; rs2241164, P = 0.0225, OR = 1.219). SNP rs2241164 was also nominally significant in the independent replication sample (P = 0.0462, OR = 1.110), and the significance became stronger in a subsequent meta-analysis combining both discovery and replication samples (P = 0.00398, OR = 1.138). Nevertheless, such association could not survive multiple corrections, although the effect size of rs2241164 was comparable with other SZ risk loci identified in genome-wide association studies (GWAS) in Han Chinese population. We also examined the associations between GAD1 SNPs and SZ in published datasets of SZ GWAS in East Asians and Europeans, and no significant associations were observed.ConclusionWe observed weak associations between GAD1 SNPs and risk of SZ in Han Chinese populations. Further analyses in larger Han Chinese samples with more detailed phenotyping are necessary to elucidate the genetic correlation between GAD1 SNPs and SZ.

Project description:BACKGROUND: The expression of ?-opioid receptor has important role in cognitive dysfunction in Schizophrenia (SZ). The results of studies about the association of polymorphisms of ?-opioid receptor gene (OPRM1) with SZ were inconsistent. METHODS: We conducted a case-control study to investigate the genetic association between OPRM1 polymorphisms and SZ among the Han chinese population. 264 SZ patients and 264 age-matched control subjects were recruited. Four SNPs of OPRM1 were successfully genotyped by using PCR-RFLP. RESULTS: Of four polymorphisms, rs1799971 and rs2075572 were shown to associate with SZ. Compared with the A allele of rs1799971 and C allele of rs2075572, the G allele of rs1799971 and rs2075572 was associated with an almost 0.46-fold risk (OR=0.46, 95% CI: 0.357-0.59, P<0.01) and 0.7-fold risk (OR=0.707, 95% CI: 0.534-0.937, P=0.015) of the occurrence of SZ,. When subjects were divided by gender, rs1799971 remained significant difference only in males (OR=0.309, 95% CI: 0.218-0.439 for G allele, P<0.01), and rs2075572 only in females (OR=0.399, 95% CI: 0.246-0.648 for G allele, P<0.01). In secondary analysis with subsets of patients, the G allele of rs1799971 (compared to the A allele) was associated with a decreased risk of all patients and male patients with apathy symptoms (OR=0.086, 95% CI: 0.048-0.151, P=0.01; OR=0.083, 95% CI: 0.045-0.153, P<0.01), and the G allele of rs2075572 (compared to the C allele) was associated with a decreased risk of all patients and female patients with positive family history (OR=0.468, 95% CI: 0.309-0.71, P<0.01; OR=0.34, 95% CI: 0.195-0.593, P<0.01). In addition, haplotype analysis revealed that two SNP haplotypes (A-C-C-G and G-C-C-A) were associated with decreased risks of SZ (P<0.01). The other two (G-C-C-G and G-G-C-G) with increased risks of SZ (P<0.01). CONCLUSIONS: The present study demonstrated for the first time that the OPRM1 polymorphism may be a risk factor for schizophrenia in the Han Chinese. Further studies are needed to give a global view of this polymorphism in pathogenesis of schizophrenia in a large-scale sample, family-based association design or well-defined subgroups of schizophrenia.

Dataset Information

Association of the CACNA2D2 gene with schizophrenia in Chinese Han population.

Publications

Association of the CACNA2D2 gene with schizophrenia in Chinese Han population.

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