The evidence of shared genetic risk factors between different psychiatric disorders has been previously interpreted as a first step in moving beyond descriptive syndromes toward a biology-informed nosology(28). A project pursuing this aim is represented by the National Institute of Mental Health’s Research Domain Criteria (RDoC), which support research examining fundamental biobehavioral dimensions that cut across current heterogeneous disorder categories(45). The present study used a similar approach and results are the first to show partially different polygenic signatures across MDD subtypes. While typical had a stronger genetic overlap with psychiatric traits, particularly with schizophrenia (2.4% explained variance), atypical MDD showed an additional contribution of genetic signals from the metabolic traits of BMI (1.2% explained variance) and triglycerides (0.5% explained variance). These findings show intriguing consistencies with previous clinical and research observations. The overlap between schizophrenia genetic risk and typical MDD is consistent with the common presence of psychotic symptoms in patients with melancholic depression(46). Furthermore, previous findings from NESDA cohort showed that patients categorized as severe typical were more likely to be smoker(15;16;18); smoking is highly comorbid with psychiatric disorders,
