The most important finding in this study is the identification of the polygenic architecture of POU that is highly comparable to the findings from GWAS of clinically ascertained OUD cohorts. We observed a positive association of POU with OUD and opioid dependence measured by two of the largest available GWAS, MVP, and PGC, and with a GWAS of opioid medication use in UKB participants. As might have been expected, we also observed strong positive genetic correlations with alcohol dependence and tobacco smoking, as well as with various psychiatric traits associated with OUD, including mood swings, risk-taking, anxiety, depression, and insomnia. These sets of genetic correlations mirror those from previous GWAS of clinically ascertained OUD samples [6–8]. However, we also showed that the overlap is not complete, and whether POU could be an early manifestation of risk for subsequent OUD is not directly explored by our study.
