The pattern of associations for rs3778150 with subjective response to alcohol and levels of alcohol use is consistent with prior observations that the rs3778150-C minor allele is associated with decreased OPRM1 expression levels in the human brain and increased risk for heroin addiction (Hancock et al., 2015). In their study, Hancock and colleagues suggested that the usual compensatory mechanism to upregulate OPRM1 expression in response to heroin exposure is disrupted by the presence of the rs3778150-C allele, necessitating increased use to acquire similar effects and thus increasing liability for addiction. Given the hypothesis that the endogenous opioid system modulates the reinforcing effects of alcohol, the results from the current study suggest that rs3778150 may directly influence a person’s subjective response to alcohol and subsequently increase risk for higher levels of alcohol use via similar mechanisms. Though rs1799971 did not show consistent association with any measure of subjective response to alcohol or alcohol consumption, this again replicates findings from Hancock et al. (2015) and lends further support to suggestions that specific haplotypes carrying noncoding regulatory variants may account for the lack of replicable associations observed for rs1799971 with substance use phenotypes (Levran et al., 2011; Zhang et al., 2006).
