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

Area of Science:

• Neurogenetics
• Psychiatric Genomics

Background:

• Genome-wide association studies (GWAS) suggest the GRM3 gene may harbor schizophrenia risk variants.
• Previous meta-analyses have not consistently supported an association between GRM3 single-nucleotide polymorphisms (SNPs) and schizophrenia risk.

Purpose of the Study:

• To reconcile conflicting findings regarding the association between GRM3 genetic variants and schizophrenia risk.
• To conduct the largest and most comprehensive meta-analysis of GRM3 SNPs and schizophrenia.

Main Methods:

• Meta-analysis of 14 GRM3 SNPs.
• Inclusion of 11,318 schizophrenia cases, 13,820 controls, and 486 parent-proband trios.
• Analysis of linkage disequilibrium and population stratification.

Main Results:

• Significant associations found for three GRM3 SNPs: rs2237562 (OR=1.06), rs13242038 (OR=0.90), and rs917071 (OR=0.94).
• Two significant SNPs (rs2237562, rs917071) showed linkage disequilibrium with the top GRM3 GWAS SNP (rs12704290).
• Evidence of population stratification for rs2237562, with risk allele varying by population.

Conclusions:

• The findings support the GWAS-implicated link between GRM3 genetic variation and schizophrenia risk.
• The study suggests that genetic risk alleles for schizophrenia associated with GRM3 may be population-specific.