Although evidence for GxE on substance use behavior has been well established, translation of this research into useful risk-factor targets for public health and clinical intervention is lacking. Among the reasons is the complex etiology of cannabis use and problems, which involves multiple genetic and psychosocial influences, each having very subtle effects. Despite this challenge, evidence for the influence of GxEs on substance use behaviors is mounting. In this study, we show that polygenic liability to cannabis ever use predicted cannabis use but not progression to DSM-5 CUDsx in COGA. However, this accounts for an extremely limited (∼0.2%) portion of the total variance in cannabis use. Among the trauma exposed, this increased to ~1.4% of the total variance in cannabis use. Given the limited predictive utility of current genetic information for cannabis use and CUD, it is important to note that both of the psychosocial contexts measured in this study explained a significantly greater portion of the variance in CUD as compared with the PRS (trauma exposure R2: 0.026; frequency of service attendance R2: 0.058). Findings from this study suggest
