Genomic SEM was used to investigate relationships between MDD-META and 15 other mental health and neurocognitive phenotypes (Figure 4, Supplementary File 3); summary statistics come from the largest studies available. All traits tested except anorexia nervosa loaded onto at least one factor during exploratory analysis. We identified three factors, with MDD-META loading onto the first two independently of covariance with the other phenotypes. Factor 1 may be thought to represent internalizing phenotypes, with major contributions from MDD-META, anxiety symptoms, and posttraumatic stress disorder. MDD-META also loaded (but less strongly) onto factor 2, which broadly represents externalizing phenotypes and psychosis, with the major contributions coming from risky behavior and cannabis use disorder. MDD-META did not load onto factor 3, which was mostly contributed to by educational attainment and cognitive performance and thus may represent a neurocognitive domain. Many cross-disorder studies using GWAS, this one included, align themselves in ways consistent with existing theories of psychopathology.
