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Meta-analysis of GABRB2 polymorphisms and the risk of schizophrenia combined with GWAS data of the Han Chinese population and psychiatric genomics consortium.

ABSTRACT: Schizophrenia (SCZ) is a severe psychiatric disorder with evidence of a strong genetic component in the complex etiologies. Some studies indicated that gamma-aminobutyric acid (GABA)A receptor ?2 subunit gene (GABRB2) was associated with SCZ. Other studies reported a negative association. Moreover, the results of two previous meta-analyses of GABRB2 with SCZ were inconsistent and the sample sizes were limited. Therefore, an updated meta-analysis combined with genome-wide association study (GWAS) data of the Han Chinese population and Psychiatric Genomics Consortium (PGC) was performed. Available case-control and family-based genetic data were extracted from association studies, and the GWAS data were included. The findings showed no association between six single-nucleotide polymorphisms of GABRB2 (rs6556547, rs1816071, rs1816072, rs194072, rs252944, and rs187269) and SCZ in a total of 51,491 patients and 74,667 controls. The ethnic subgroup analysis revealed no significant association in Asian populations. Since the PGC data of SCZ (SCZ-PGC, 2014) contained 3 studies of Asian populations (1866 patients and 3418 controls), only the data of European samples in SCZ-PGC were used for the meta-analysis of the Caucasian population in the present study. The result still showed no association in the Caucasian population. In conclusion, the present meta-analysis on combined data from GWASs of the Han Chinese population and PGC suggested that GABRB2 polymorphisms might not be associated with SCZ.

SUBMITTER: Zhang T

PROVIDER: S-EPMC5997335 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Meta-analysis of GABRB2 polymorphisms and the risk of schizophrenia combined with GWAS data of the Han Chinese population and psychiatric genomics consortium.

Zhang Tian T Li Jun J Yu Hao H Shi Yongyong Y Li Zhiqiang Z Wang Linyan L Wang Ziqi Z Lu Tianlan T Wang Lifang L Yue Weihua W Zhang Dai D

PloS one 20180612 6

Schizophrenia (SCZ) is a severe psychiatric disorder with evidence of a strong genetic component in the complex etiologies. Some studies indicated that gamma-aminobutyric acid (GABA)A receptor β2 subunit gene (GABRB2) was associated with SCZ. Other studies reported a negative association. Moreover, the results of two previous meta-analyses of GABRB2 with SCZ were inconsistent and the sample sizes were limited. Therefore, an updated meta-analysis combined with genome-wide association study (GWAS) ...[more]

PMID: 29894498

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Project description:While 17% of US adults use tobacco regularly, smoking rates among persons with schizophrenia are upwards of 60%. Research supports a shared etiological basis for smoking and schizophrenia, including findings from genome-wide association studies (GWAS). However, few studies have directly tested whether the same or distinct genetic variants also influence smoking behavior among schizophrenia cases. Using data from the Psychiatric Genomics Consortium (PGC) study of schizophrenia (35476 cases, 46839 controls), we estimated genetic correlations between these traits and tested whether polygenic risk scores (PRS) constructed from the results of smoking behaviors GWAS were associated with schizophrenia risk or smoking behaviors among schizophrenia cases. Results indicated significant genetic correlations of schizophrenia with smoking initiation (rg = 0.159; P = 5.05 × 10-10), cigarettes-smoked-per-day (rg = 0.094; P = 0.006), and age-of-onset of smoking (rg = 0.10; P = 0.009). Comparing smoking behaviors among schizophrenia cases to the general population, we observe positive genetic correlations for smoking initiation (rg = 0.624, P = 0.002) and cigarettes-smoked-per-day (rg = 0.689, P = 0.120). Similarly, TAG-based PRS for smoking initiation and cigarettes-smoked-per-day were significantly associated with smoking initiation (P = 3.49 × 10-5) and cigarettes-smoked-per-day (P = 0.007) among schizophrenia cases. We performed the first GWAS of smoking behavior among schizophrenia cases and identified a novel association with cigarettes-smoked-per-day upstream of the TMEM106B gene on chromosome 7p21.3 (rs148253479, P = 3.18 × 10-8, n = 3520). Results provide evidence of a partially shared genetic basis for schizophrenia and smoking behaviors. Additionally, genetic risk factors for smoking behaviors were largely shared across schizophrenia and non-schizophrenia populations. Future research should address mechanisms underlying these associations to aid both schizophrenia and smoking treatment and prevention efforts.

Project description:BackgroundThe expression of μ-opioid receptor has important role in cognitive dysfunction in Schizophrenia (SZ). The results of studies about the association of polymorphisms of μ-opioid receptor gene (OPRM1) with SZ were inconsistent.MethodsWe 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.ResultsOf 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).ConclusionsThe 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.

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Dataset Information

Meta-analysis of GABRB2 polymorphisms and the risk of schizophrenia combined with GWAS data of the Han Chinese population and psychiatric genomics consortium.

Publications

Meta-analysis of GABRB2 polymorphisms and the risk of schizophrenia combined with GWAS data of the Han Chinese population and psychiatric genomics consortium.

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