based on more homogenous symptom profiles have been proposed: typical/melancholic and atypical(11), reflected in the DSM-5 specifiers for melancholic and atypical depression. However, not all DSM criteria have been justified by research, and recent studies based on data-driven techniques highlighted the importance of vegetative symptoms (particularly appetite and weight) in distinguishing subtypes (decreased in typical, increased in atypical)(12–17). Increasing evidence suggests that subtypes are associated with different pathophysiological correlates: environmental stress (e.g. childhood trauma), smoking and HPA-axis hyperactivity appear more specific for typical depression, while obesity, metabolic dysregulations (e.g. abdominal adiposity, hypertriglyceridemia) and inflammation up-regulations appear more specific for atypical depression(11;18;19). In line with this observation, we recently showed(20) that the association between a variant in the FTO gene and MDD was completely driven by the atypical subtype. Based on these findings we hypothesized that MDD subtypes may be characterized by a partially distinct genetic liability, with genetic profiles for stress-related and psychiatric traits more specifically linked with typical MDD, and those for obesity-related metabolic dysregulations with atypical MDD. We tested our hypothesis in a sample of 3,230 Dutch adults with established psychiatric diagnoses and GWAS data. We examined for MDD and its subtypes: 1) the genetic overlap with major
