The top finding of this gSEM GWAS for OA was centered in intron 1 of the OPRM1 gene (lead SNP rs9478500-C). Prior candidate gene studies of this region have found nominal associations of variants in intron 1, including some of those that are GWS here (e.g., rs1381376, rs3778151, & rs3778150)39,51,52. The mu-opioid receptor gene, OPRM1, has long been a target of OA research and drug development. The functional coding variant rs1799971 (A118G; Asn40Asp) has been studied at length with equivocal results39,53,54. In the current GWAS era, only the MVP GWAS of OUD found rs1799971 to be GWS (p = 1.51 × 10–8)27. Adding cohorts to the MVP summary statistics in the current study reduced the variant’s association with OA to p = 1.94 × 10–6.
