The largest study to date44 incorporated MVP and Yale–Penn data, and included over 114,000 informative EUR and AA subjects in total. This study identified significant association of OUD with a well-known functional OPRM1 variant, A118G (Asn40Asp) — even in the largest study to date there was only one clear GWS finding. OPRM1 encodes the μ opioid receptor gene, considered the main biological target of opioid drugs. Opioids such as methadone and morphine are full agonists at the μ-opioid receptor. OPRM1 has been the subject of intense interest, particularly this same common missense A118G SNP. Opioid dosing in therapeutic contexts is important clinically, and another GWAS considered the trait of methadone dose45. In AAs only, this study identified a significant association of methadone dose to a variant upstream of OPRM1, thus it could possibly have an effect through the same gene as that identified in the largest-to-date GWAS. The sample size for this latter study was very small and the results could be a false positive, but the proximity of this signal to the OUD GWAS signal is intriguing.
