We conducted a PheWAS with EHR data to test the association between polygenic risk for POU and liability across thousands of medical conditions from hospital-based cohorts. Our PheWAS identified significant associations between POU and 53 medical traits across 13 categories (i.e., psychiatric disorders, respiratory, circulatory system, symptoms, sense organs, dermatologic, injuries and poisonings, neurological, digestive, infectious diseases, neoplasms, genitourinary, endocrine/metabolic; Supplementary Table 18 and Fig. 5). Similar to the genetic correlations, the strongest associations were with substance use disorders, including tobacco use disorder (OR = 1.15, p = 7.47E−25), alcohol-related disorders (OR = 1.12, p = 7.69E−05) and substance addiction and disorders (OR = 1.17, p = 4.67E−12), which included both opiates and other substances.
