The endogenous opioid system has been hypothesized to partially mediate the reinforcing properties of alcohol, and there has been a longstanding interest in how variation in the gene encoding the μ-opioid receptor (OPRM1) relates to measures of alcohol consumption and dependence. Numerous studies have tested genetic variation in OPRM1 for association with these phenotypes, but have yielded few replicable, robust findings. Much of the existing research has focused on a missense variant in OPRM1, rs1799971; however, recent evidence suggests that a second OPRM1 variant, rs3778150, may be accounting for the mixed findings observed for heroin and other opioid use (Hancock et al., 2015). In the aforementioned study, the rs3778150-C allele was only observed in the presence of the rs1799971-A allele. This haplotype was significantly associated with liability for heroin addiction across European American and African American individuals, as well as in a meta-analysis; however, in the absence of rs3778150-C, the rs1799971-A allele showed no association with heroin addiction in either ancestral group or in a meta-analysis. Therefore, their findings suggested that the association of rs1799971 with heroin addiction was dependent
