Substance use disorders (SUDs) are associated with substantial cost to affected individuals, their families, and society at large.1,2 Twin and family studies estimate the heritability of individual SUDs, including alcohol,3 cannabis,4 and opioid use disorders,5 to be around 50%, with a large portion of the heritability for each disorder shared across different substances.5 SUDs co-occur with other forms of psychopathology, personality and behavioural traits,6 most notably with disorders and traits characterized by under-controlled or impulsive action, often termed externalizing phenotypes.7,8 These phenotypes include psychiatric disorders, such as attention-deficit hyperactivity disorder (ADHD), conduct disorder, oppositional defiant disorder (ODD) and antisocial personality disorder,9,10 as well as personality and behavioural traits like risk taking,11 aggression,12 lack of constraint8 and antagonism.13 Mirroring phenotypic associations, SUDs are also genetically correlated with externalizing phenotypes.14–17
