The mu-opioid receptor (MOR) is encoded by the OPRM1 gene. Activation of MOR signaling by endogenous peptides (e.g. beta-endorphin), opioid analgesics, or illicit drugs results in downstream dopamine release in ventral striatum and medial prefrontal cortex and rewarding effects. OPRM1 polymorphisms that affect MOR function or expression could alter this reward pathway and are therefore strong candidates for affecting OUD risk. There are two common variants in exon 1 of OPRM1 that alter the MOR amino acid sequence: rs1799972, which is found predominantly in individuals of African descent, and rs1799971 (aka A118G), which is common in all non-African populations. Although there is a wealth of evidence indicating that rs1799971 genotype affects MOR function [3–6], case-control studies of this variant in OUD have produced equivocal results. Many of these studies have found no effect of the variant across multiple populations of African, Asian, or European ancestry [7–12], though some significant associations have been noted [3, 13–15]. A meta-analysis from 2009 found no association between rs1799971 and OUD, but noted substantial variability between cohorts that could be the result of methodological differences or genetic background [16].
