Eight genome-wide association studies (GWAS) of OA have been reported21–28, in which the number of cases varied from 104 to 10,544 for ancestry specific analyses. Six of these GWAS identified genome-wide significant (GWS) loci23,25–29. However, only the largest analysis, which combined results of European ancestry (EA) cohorts from the US Veterans Affairs Million Veteran Program (MVP), the Study of Addiction: Genetics and Environment (SAGE), and Yale-Penn (YP) cohorts (10,544 cases and 72,163 controls), identified a GWS association that replicated in an independent sample (additional YP data: 508 cases and 206 controls). The variant identified is the long-studied rs1799971 (OPRM1-A118G), a functional coding variant (encoding Asn40Asp) in the mu opioid receptor gene (OPRM1): discovery p = 1.51 × 10−8, replication p = 0.049. The rs1799971-G protective association with OA was also extended at nominal significance to buprenorphine treatment status in the UK Biobank (240 cases and 360,901 controls; p = 0.04).
