Both cannabis use and CUDs are complex genetic traits, influenced by multiple genetic variants of small effect (i.e., polygenicity) and aspects of the psychosocial environment (e.g., religiosity, trauma), which act independently and in concert. However, this information has not been effectively incorporated into genetic association studies. Polygenic risk scores (PRS), which aggregate genetic variants to reflect the underlying structure of complex traits, have been increasingly used to model the genetic architecture of substance use disorders12,13,27–30. In addition to the potential for identifying genetic risk markers for cannabis involvement31,32, these methods enable researchers to identify potential psychosocial mechanisms that modify genetic associations with CUD. Given that current findings from psychiatric genomics research are not yet at the point of clinical utility, identifying modifiable psychosocial risk and protective factors may be useful for downstream use in clinical and translational sciences.
