An intriguing omission among the depression-associated genes identified in our study are genes linked with the serotonergic system, such as the serotonin transporter SLC6A4; the G protein subunit GNB3; the serotonin receptor HTR2A and tryptophan hydroxylase (TPH2). This is surprising, as interaction with the serotonergic system forms the basis of most antidepressant treatments. Our finding could indicate a functional separation between genetic pathways of depressive disease and pathways of antidepressant treatment. Thus, serotonin-associated genes, while potentially relevant for predicting efficacy and adverse effects of serotonergic antidepressants, may not be directly associated with the aetiology of depression itself (or at least that which is determined by common genetic variation identified in GWAS). Indeed, a recent review of the genetics studies of depression has remarked upon the failure to demonstrate association with depression for serotonergic and other popular candidate genes 49. It may also be that the pathways of depression and serotonergic antidepressant effect are separate but entwine through common intermediary genes. One such candidate is NRG1, identified here in depression, and also in a recent meta-analysis of antidepressant response 50. These
