The current study sought to test this hypothesis, and in this way, extend the findings from (Hancock et al., 2015) to evaluate the relations of genetic variation in OPRM1 with alcohol use and measures of subjective response to alcohol. Given that rs1799971 was not significantly associated with heroin addiction in the absence of rs3778150, and rs3778150 was associated with both heroin addiction and reduced OPRM1 mRNA expression in the brain (Hancock et al., 2015), including these variants in association studies could potentially clarify the effect of rs1799971 on alcohol use phenotypes. The association of rs3778150 with reduced OPRM1 mRNA expression in the brain might reflect a genetic predisposition that reduces normal compensatory mechanisms in response to heroin exposure, requiring more of the substance to evoke a physiological effect and subsequently increased risk of addiction (Hancock et al., 2015). As such, we predicted that rs3778150 would be associated with lower subjective response to alcohol and higher levels of alcohol use, over and above any effects of rs1799971.
