These genes include GRM7, previously associated to major depression disorder and bipolar disorder, SLC6A13, in anxiety disorders, and S100B, SSTR5 and COMT in schizophrenia.
There is increasing evidence to suggest that metabotropic glutamate (mGlu) receptors including mGlu(7) receptor are important in the pathophysiology of stress-related psychiatric disorders such as anxiety and major depression. mGlu(7) receptor is highly expressed in the hippocampus, a key region involved in the modulation of depression-related behaviour.
A meta-analysis of 3,957 case subjects with major depressive disorder and 3,428 control subjects from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D), Genetics of Recurrent Early-onset Depression (GenRED), and the Genetic Association Information Network-MDD (GAIN-MDD) data sets demonstrated a region of association for major depressive disorder within GRM7.
We aimed to gather more evidence that rs2522833 is indeed the causal variant in the GAIN-MDD cohort or to find a previously undetected common variant in either PCLO, GRM7, or SLC6A4 with a higher association in this cohort.