GRM7 encodes metabotropic glutamate receptor 7 (mGluR7), which may be involved in mood regulation55, 56. Chronic treatment with mood stabilizers (lithium or valproate) decreased a hippocampal micro-RNA, increasing GRM7 expression.57 An mGluR7 agonist (AMN082) had antidepressant-like effects in mice that were blocked by knockout of GRM758, and chronic antidepressant treatment with citalopram in rodents decreased mGluR7 immunoreactivity in hippocampus and frontal cortex59. This is the third GWAS to report evidence of association to mood disorders in this long gene (880 kb). Our lowest P-value (7.11 × 10−7) was at 7.5 Mb (3p26.1), with P-values less than 10−4 extending to 7.56 Mb. In the German/Swiss recurrent MDD GWAS16, the lowest P-value (0.0001) was at 7.68 Mb, with P-values around 0.01 overlapping our signals. In the Wellcome Trust Case-Control Consortium bipolar disorder GWAS60, the best P-value in GRM7 (0.0001 in a genotypic analyses) was at 7.63 Mb. Larger samples will be required to determine the significance of these findings, but the biological evidence suggests that GRM7 merits further investigation.
