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

• Published in: Translational psychiatry Vol. 7; no. 8; p. e1196
• Main Authors: Saini, S M, Mancuso, S G, Mostaid, Md S, Liu, C, Pantelis, C, Everall, I P, Bousman, C A
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 08-08-2017; Nature Publishing Group
• Subjects: 45; 631/208; 692/53/2421; Alleles; Behavioral Sciences; Biological Psychology; Gene Frequency; Genetic Predisposition to Disease; Genome-Wide Association Study; Genotype; Humans; Medicine; Medicine & Public Health; Meta-analysis; Neurosciences; Original; original-article; Pharmacotherapy; Polymorphism; Polymorphism, Single Nucleotide; Psychiatry; Receptors, Metabotropic Glutamate - genetics; Schizophrenia; Schizophrenia - genetics
• ISSN: 2158-3188; 2158-3188
• DOI: 10.1038/tp.2017.172

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.