Dopamine release and post-synaptic receptor activation underlies the rewarding effects of opioids. DRD2 encodes the dopamine D2 receptor and is located <10kb downstream of ANKK1, a gene encoding a serine/threonine protein kinase. The DRD2/ANKK1 locus contains two commonly studied polymorphisms: rs1800497 (aka Taq1A), a missense variant in exon 8 of ANKK1, and rs1079597 (aka Taq1B), located in intron 1 of DRD2. Rs1800497 and rs1079597 are in relatively high linkage disequilibrium (r2 = 0.5-1.0) in almost all non-African populations, meaning the two variants are inherited together more often than would be expected by chance in those ethnic groups [25]. Both variants have been associated with opioid dependence in Han Chinese [26–28], with one study noting that the effect was largest in subjects who developed opioid dependence later in life [26]. Significant associations for rs1800497 and rs1079597 have also been found in Europeans (case n = 303, control n = 555) [29]. Meta-analyses from 2015 (case n = 3423, control n = 3096) and 2018 (case n = 4529, control n = 4168) both found a small effect of rs1800497 on OUD
