DNA sequence variants in the metabotropic glutamate receptor 3 and risk to schizophrenia: an association study

OBJECTIVES: Recent studies investigating the association of DNA variants in the metabotropic glutamate receptor gene (GRM3) with schizophrenia susceptibility revealed conflicting results. In this study, we focused on DNA sequence variants, for which association was reported and attempted to replicate association with schizophrenia or with cognitive deficits known to be present in patients with schizophrenia. METHODS: A sample of 242 families with affected offspring and five single nucleotide markers located in the genomic region of GRM3 has been used to replicate association with schizophrenia. In addition, results of neuropsychological tests, trail making test B and the Stroop color-naming task were available for a subgroup of these families (N=88) and an independent sample of 148 patients with schizophrenia. Correlation of these measurements with genotypic data was performed using analysis of variance. RESULTS: No statistical evidence for association with schizophrenia or correlation with cognitive deficits as measured by the trail making test B or the Stroop color-naming task and the five DNA sequence variants could be detected. A trend towards association with schizophrenia was revealed for a single marker (rs2237562, P=0.056) and for 2-marker and 3-marker haplotypes containing this variant. CONCLUSIONS: Our study of DNA sequence variants in the GRM3 gene did not provide further support for genetic association with schizophrenia or for correlation with cognitive deficits.