In this study, we performed a GWAS of problematic opioid use (‘ever taking prescription painkillers not as prescribed’) in 132,113 23andMe research participants of European ancestry. This represented a novel approach to studying OUD in a population-based cohort. Our results show that this single question captured a genetic signal that is correlated with signals from well-characterized cohorts that have been clinically diagnosed with OUD. Notably, the genetic correlations with OUD persisted even after correcting for risk-taking behavior and other putatively similar dimensional phenotypes. We also identified novel associations with laboratory-based biomarkers, demonstrating the overarching impact of POU on health. While previous GWAS of OUD have used clinically ascertained cohorts, our results suggest that POU provides a cost-effective alternative to diagnosed OUD that is viable in non-clinically ascertained populations, making it possible to rapidly obtain large sample sizes that can aid in OUD gene discovery.
