A new lead from genetic studies in depressed siblings: assessing studies of chromosome 3

Studies by Breen et al. and Pergadia et al. find evidence for genetic linkage between major depressive disorder and the same region on chromosome 3. The linked region contains the gene GRM7, which encodes a protein for the metabotropic glutamate receptor 7 (mGluR7). Both studies used affected sibling pairs, and neither was able to replicate its finding using association studies in individuals from larger population-based studies. Other family-based studies have also failed to find a signal in this region. Furthermore, there are some differences in how the phenotype was classified, with Breen et al. finding evidence only in the most severely affected patients. Nonetheless, the finding is not without other substantive support. 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. Thus, the significance of this finding remains uncertain, although it points to a gene that might hold significant promise for further developments in studying the pathophysiology and treatment of major depressive disorder.