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Evaluation of a susceptibility gene for schizophrenia: genotype based meta-analysis of RGS4 polymorphisms from thirteen independent samples.

ABSTRACT: Associations between schizophrenia (SCZ) and polymorphisms at the regulator of G-protein signaling 4 (RGS4) gene have been reported (single nucleotide polymorphisms [SNPs] 1, 4, 7, and 18). Yet, similar to other SCZ candidate genes, studies have been inconsistent with respect to the associated alleles.In an effort to resolve the role for RGS4 in SCZ susceptibility, we undertook a genotype-based meta-analysis using both published and unpublished family-based and case-control samples (total n = 13,807).The family-based dataset consisted of 10 samples (2160 families). Significant associations with individual SNPs/haplotypes were not observed. In contrast, global analysis revealed significant transmission distortion (p = .0009). Specifically, analyses suggested overtransmission of two common haplotypes that account for the vast majority of all haplotypes. Separate analyses of 3486 cases and 3755 control samples (eight samples) detected a significant association with SNP 4 (p = .01). Individual haplotype analyses were not significant, but evaluation of test statistics from individual samples suggested significant associations.Our collaborative meta-analysis represents one of the largest SCZ association studies to date. No individual risk factor arose from our analyses, but interpretation of these results is not straightforward. Our analyses suggest risk due to at least two common haplotypes in the presence of heterogeneity. Similar analysis for other putative susceptibility genes is warranted.

SUBMITTER: Talkowski ME

PROVIDER: S-EPMC3133764 | biostudies-literature | 2006 Jul

REPOSITORIES: biostudies-literature

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Evaluation of a susceptibility gene for schizophrenia: genotype based meta-analysis of RGS4 polymorphisms from thirteen independent samples.

Talkowski Michael E ME Seltman Howard H Bassett Anne S AS Brzustowicz Linda M LM Chen Xiangning X Chowdari Kodavali V KV Collier David A DA Cordeiro Quirino Q Corvin Aiden P AP Deshpande Smita N SN Egan Michael F MF Gill Michael M Kendler Kenneth S KS Kirov George G Heston Leonard L LL Levitt Pat P Lewis David A DA Li Tao T Mirnics Karoly K Morris Derek W DW Norton Nadine N O'Donovan Michael C MC Owen Michael J MJ Richard Christian C Semwal Prachi P Sobell Janet L JL St Clair David D Straub Richard E RE Thelma B K BK Vallada Homero H Weinberger Daniel R DR Williams Nigel M NM Wood Joel J Zhang Feng F Devlin Bernie B Nimgaonkar Vishwajit L VL

Biological psychiatry 20060421 2

<h4>Background</h4>Associations between schizophrenia (SCZ) and polymorphisms at the regulator of G-protein signaling 4 (RGS4) gene have been reported (single nucleotide polymorphisms [SNPs] 1, 4, 7, and 18). Yet, similar to other SCZ candidate genes, studies have been inconsistent with respect to the associated alleles.<h4>Methods</h4>In an effort to resolve the role for RGS4 in SCZ susceptibility, we undertook a genotype-based meta-analysis using both published and unpublished family-based and ...[more]

PMID: 16631129

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Project description:BackgroundAccumulating studies have reported inconsistent association between ErbB4 single nucleotide polymorphisms (SNPs) and predisposition to schizophrenia. To better interpret this issue, here we conducted a meta-analysis using published case-control studies.MethodsWe conducted a systematic search of MEDLINE (Pubmed), Embase (Ovid), Web of Science (Thomson-Reuters) to identify relevant references. The association between ErbB4 SNPs and schizophrenia was assessed by odds ratios (ORs) and 95% confidence intervals (CIs). Between-study heterogeneity was evaluated by I squared (I) statistics and Cochran's Q test. To appraise the stability of results, we employed sensitivity analysis by omitting 1 single study each time. To assess the potential publication bias, we conducted trim and fill analysis.ResultsSeven studies published in English comprising 3162 cases and 4264 controls were included in this meta-analysis. Meta-analyses showed that rs707284 is statistically significantly associated with schizophrenia susceptibility among Asian and Caucasian populations under the allelic model (OR = 0.91, 95% CI: 0.83-0.99, P = 0.035). Additionally, a marginal association (P < 0.1) was observed between rs707284 and schizophrenia risk among Asian and Caucasian populations under the recessive (OR = 0.85, 95% CI: 0.72-1.01, P = 0.065) and homozygous (OR = 0.84, 95% CI: 0.68-1.03, P = 0.094) models. In the Asian subgroup, rs707284 was also noted to be marginally associated with schizophrenia under the recessive model (OR = 0.84, 95% CI: 0.70-1.00, P = 0.053). However, no statistically significant association was found between rs839523, rs7598440, rs3748962, and rs2371276 and schizophrenia risk.ConclusionThis meta-analysis suggested that rs707284 may be a potential ErbB4 SNP associated with susceptibility to schizophrenia. Nevertheless, due to the limited sample size in this meta-analysis, more large-scale association studies are still needed to confirm the results.

Dataset Information

Evaluation of a susceptibility gene for schizophrenia: genotype based meta-analysis of RGS4 polymorphisms from thirteen independent samples.

Publications

Evaluation of a susceptibility gene for schizophrenia: genotype based meta-analysis of RGS4 polymorphisms from thirteen independent samples.

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