Relatedly for opioid use disorder phenotypes, two GWAS of clinical opioid dosing have been reported [115, 116]. Most recently, a genome-wide significant association of methadone dosing among 383 opioid-dependent African Americans was observed for the SNP rs73568641 (P=2.8×10−8), located upstream of OPRM1 [116]. The rs73568641 association was extended to morphine dosing for post-operative pain in an independent dataset of 241 African Americans (P=0.039) [116]. Rs73568641 is in weak linkage disequilibrium (r2<0.01 and D′=0.54 across 1000 Genomes African ancestry reference panels [117]) with the cis-eQTL SNP rs3778150, suggesting that variants marking more than one signal across the OPRM1 gene region may be driving different opioid phenotypes. However, association analyses of these SNPs conditioned on one another are needed to formally assess independence of the signals.
