The associated locus on chromosome 6 was centered in intron 1 of the mu-opioid receptor gene OPRM1 (Supplementary Fig. 11). The minor allele of the lead variant, rs9478500-C, was associated with increased risk of OA (beta = 0.136). All of the GWS variants were in high linkage disequilibrium (LD) with each other (r2 > 0.88 and D’ > 0.93; Supplementary Table 9). The previously reported missense variant rs1799971 (OPRM1-A118G), which was GWS for OUD in MVP-SAGE-YP27, was less statistically significant in our gSEM analysis (rs1799971-G, beta = − 0.115, p = 1.94 × 10–6; forest plot Supplementary Fig. 9b). In the MVP GWAS rs9478500-C was associated with OA, but with less statistical significance (MVP rs9478500-C, beta = 0.09, p = 4.31 × 10–5).
