The current analyses revealed four correlated psychiatric factors that account for extensive genetic overlap across disorders. We elucidate the composition of these factors by demonstrating patterns of correlations with external biobehavioral traits, develop and apply Stratified Genomic SEM to identify classes of genes that explain disproportionate levels of genetic risk sharing and uniqueness, and distinguish pleiotropic loci with directionally concordant effects on the individual factors from those acting heterogeneously across disorders within a factor. Our results offer critical insights into shared and disorder specific mechanisms of genetic risk and suggest possible avenues for revising a psychiatric nosology currently defined largely by clinical observation. Evidence derived from multivariate genetic analysis, alongside evidence at other levels of explanation (e.g., cognitive neuroscience, environmental stressors), could guide the development of novel treatments and revision of established diagnostic taxonomies.
