Taken together, our results indicate the utility of complementary strategy to intensive phenotyping for identifying common variant associations with phenotypically heterogeneous neuropsychiatric diseases. The inter-rater reliability of lifetime MDD diagnosis even with structured interview is modest, with a kappa of 0.32–0.5723,24; conversely, the reliance on treatment-seeking patients in the present analysis rather than volunteers responding to advertisements lends additional face validity to the phenotype25. The finding in other large-scale analyses that cohorts ascertained based on treatment rather than structured interview yield similar associations12, and that such phenotypes are consistent with structured interview26, adds confidence to the validity of this approach12. In light of the massive impact of such disorders on health worldwide, any approach that can help elucidate pathophysiology merits consideration. The finding that a locus previously linked to other neuropsychiatric disease increases MDD risk also adds to a burgeoning literature indicating the pleiotropy of such risk genes.
