To provide a fuller examination of OPRM1 variation in relation to substance use phenotypes, a recent study sought to narrow the focus to variants presumed to alter OPRM1 messenger RNA expression (mRNA) in the brain (Hancock et al., 2015). Their findings suggested that a variant located in close proximity to rs1799971 within a highly conserved region of OPRM1, rs3778150, is robustly associated with heroin addiction, and notably is in partial linkage disequilibrium (LD) with rs1799971. The rs3778150-C allele was associated with decreased OPRM1 expression levels in the human brain, and further, the association with rs3778150 fully explained a smaller observed association with rs1799971 (Hancock et al., 2015). They concluded that rs3778150 may represent a causal variant within OPRM1 that increases risk for heroin addiction, thus providing a potential explanation for the mixed results reported in the broader substance use literature regarding the latter variant.
