Using bivariate MiXeR, we found extensive genetic overlap across mental disorders and cognitive and personality traits. This pattern was present in scenarios of weak genome-wide genetic correlation, such as MD and cognition, as well as strong genome-wide correlations, such as BIP and schizophrenia. The former is indicative of a balance of shared variants with concordant and discordant effect directions on each trait, a pattern we replicate using LAVA. These findings build on previous evidence demonstrating extensive genetic overlap between SCZ, BIP, MD and intelligence, with widespread mixed effect directions.11,17 Together, this indicates that most common variants which influence the genetic risk for diverse mental phenotypes are highly pleiotropic and may have both risk-enhancing and risk-reducing effects on different disorders and traits. Consequently, it may be the specific distribution of effect sizes of highly pleiotropic variants which predominantly contribute to the development of a given mental disorder rather than a set of phenotype-specific variants.
