(FDR: P = .018, P = .042, and P = .040, respectively).Our results indicated that genetic variants in the GRIK4 and GRM7 may associate with the treatment response in MDD patients treated by venlafaxine.
Three samples with major depressive disorder (total=671) were genotyped for 44 SNPs in 8 candidate genes (CACNA1C, CACNB2, ANK3, GRM7, TCF4, ITIH3, SYNE1, FKBP5).
Variants within three genes, BICC1, PCLO and GRM7 were selected for replication in our study based on the following criteria: they were identified in a prior MDD GWAS study; a subsequent study found evidence that they influenced depression risk; and there is a solid biological basis for a role in depression.
GRM7, ANGPT4, and LRFN5 have been previously implicated in psychiatric disorders, including the GRM7 region displaying association with major depressive disorder.
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.
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.
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.
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.
These genes include GRM7, previously associated to major depression disorder and bipolar disorder, SLC6A13, in anxiety disorders, and S100B, SSTR5 and COMT in schizophrenia.