Major Depressive Disorder (MDD) is a frequently disabling, chronic disorder for which there is substantial evidence of a genetic contribution to its liability1. Until recently, the largest international mega-analysis of clinically diagnosed MDD (9240 MDD cases and 9519 controls) yielded no genome-wide significant findings2. Given the success of similarly sized studies for other adult psychiatric disorders3,4, this study suggested that MDD is an extensively heterogeneous phenotype. This heterogeneity, in addition to the relatively high prevalence and low heritability of MDD, impacts substantially on the statistical power to detect genetic effects1,5. Possible means of improving statistical power include stratifying the phenotype into potentially more homogeneous subtypes, or considerably increasing the sample size whilst accepting a broader phenotype. Both of these approaches have since identified associations between genetic variants and MDD6–9.
