Despite evidence that SUDs share phenotypic43 and genetic8,12,18 variance with each other and with other externalizing traits, gene identification efforts continue to study individual SUDs in isolation or treat them as distinct from externalizing. This leaves potentially important genetic variance untagged and may, in part, explain the slow progress in gene discovery for certain SUDs relative to other complex behavioral phenotypes44. The role of externalizing in SUDs is also important for prevention, intervention and treatment. If SUD genetic risk largely reflects broad externalizing risk, it suggests that individuals at risk for or current experiencing an SUD are also at risk for other externalizing problems, which should be taken into account in prevention and intervention efforts. Here, we drew from the phenotypic classification and twin literature on the nature of genetic influences on SUDs5,7,12 and capitalized on recent advances in multivariate statistical genetic methods16, to model the shared genetic architecture of SUDs and other externalizing phenotypes with the goal of improving gene discovery for SUDs.
