In conclusion, polygenic liability to cannabis use was nominally associated with cannabis ever use and with progression to DSM-5 CUDsx in an independent sample of individuals enriched for substance use problems. In addition, PRSxE was observed with trauma exposure, with less consistent moderation effects observed with religious service attendance that are driven by important interactions with ancestry and sex. These findings provide the first evidence of PRSxE effects for cannabis use and support previous findings that trauma exacerbates genetic risk for substance use, while religious service attendance may serve as a protective factor. This study also demonstrates that, by not modeling important aspects of the psychosocial environment, we may mask genetic influences on polygenic traits, such as cannabis use.
