Meta-analysis supports GWAS-implicated link between GRM3 and schizophrenia risk

Suriati Mohamed Saini, S. G. Mancuso, Md S. Mostaid, C. Liu, C. Pantelis, I. P. Everall, C. A. Bousman

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Genome-wide association study (GWAS) evidence has identified the metabotropic glutamate receptor 3 (GRM3) gene as a potential harbor for schizophrenia risk variants. However, previous meta-analyses have refuted the association between GRM3 single-nucleotide polymorphisms (SNPs) and schizophrenia risk. To reconcile these conflicting findings, we conducted the largest and most comprehensive meta-analysis of 14 SNPs in GRM3 from a total of 11 318 schizophrenia cases, 13 820 controls and 486 parent-proband trios. We found significant associations for three SNPs (rs2237562: odds ratio (OR)=1.06, 95% confidence interval (CI)=1.02-1.11, P=0.017; rs13242038: OR=0.90, 95% CI=0.85-0.96, P=0.016 and rs917071: OR=0.94, 95% CI=0.91-0.97, P=0.003). Two of these SNPs (rs2237562, rs917071) were in strong-to-moderate linkage disequilibrium with the top GRM3 GWAS significant SNP (rs12704290) reported by the Schizophrenia Working Group of the Psychiatric Genomics Consortium. We also found evidence for population stratification related to rs2237562 in that the 'risk' allele was dependent on the population under study. Our findings support the GWAS-implicated link between GRM3 genetic variation and schizophrenia risk as well as the notion that alleles conferring this risk may be population specific.

Original languageEnglish
Pages (from-to)e1196
JournalTranslational psychiatry
Volume7
Issue number8
DOIs
Publication statusPublished - 8 Aug 2017
Externally publishedYes

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Genome-Wide Association Study
Single Nucleotide Polymorphism
Meta-Analysis
Schizophrenia
Odds Ratio
Confidence Intervals
Alleles
Population
Linkage Disequilibrium
Genomics
Psychiatry
Genes

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Biological Psychiatry

Cite this

Mohamed Saini, S., Mancuso, S. G., Mostaid, M. S., Liu, C., Pantelis, C., Everall, I. P., & Bousman, C. A. (2017). Meta-analysis supports GWAS-implicated link between GRM3 and schizophrenia risk. Translational psychiatry, 7(8), e1196. https://doi.org/10.1038/tp.2017.172

Meta-analysis supports GWAS-implicated link between GRM3 and schizophrenia risk. / Mohamed Saini, Suriati; Mancuso, S. G.; Mostaid, Md S.; Liu, C.; Pantelis, C.; Everall, I. P.; Bousman, C. A.

In: Translational psychiatry, Vol. 7, No. 8, 08.08.2017, p. e1196.

Research output: Contribution to journalArticle

Mohamed Saini, S, Mancuso, SG, Mostaid, MS, Liu, C, Pantelis, C, Everall, IP & Bousman, CA 2017, 'Meta-analysis supports GWAS-implicated link between GRM3 and schizophrenia risk', Translational psychiatry, vol. 7, no. 8, pp. e1196. https://doi.org/10.1038/tp.2017.172
Mohamed Saini, Suriati ; Mancuso, S. G. ; Mostaid, Md S. ; Liu, C. ; Pantelis, C. ; Everall, I. P. ; Bousman, C. A. / Meta-analysis supports GWAS-implicated link between GRM3 and schizophrenia risk. In: Translational psychiatry. 2017 ; Vol. 7, No. 8. pp. e1196.
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