We conducted PheWAS with EHR data to test the association between polygenic risk for TUD and liability for thousands of other medical conditions, including TUD, in another independent site, Mayo Clinic. As expected, TUD PGS was strongly associated with TUD (p=1.90E-145, Supplementary Table 34, Figure 6a), explaining 7.3% of the (Nagelkerke’s R2) variance. Additional significant (p<3.24–05) associations included 4 traits in the substance use disorders domain (e.g., alcohol-related disorders, OR=1.33, p=6.30E-26), 10 psychiatric conditions (e.g., depression, OR=1.09, p=4.31E-11), and medical conditions strongly associated with TUD (e.g., chronic airway obstruction, OR=1.25, p=1.60E-32). Most of these associations remained significant after accounting for TUD diagnosis (Supplementary Table 34). We also noted associations across multiple other medical categories, including endocrine/metabolic (e.g., morbid obesity, OR=1.12, p=3.53E-13; type 2 diabetes, OR=1.09, p=1.48E-09), digestive (e.g., diseases of esophagus, OR=1.07, p=1.47E-10), circulatory (e.g., ischemic heart disease, OR=1.09, p=1.56E-11) and neurologic (e.g., pain, OR=1.07, p=4.33E-08), among others (Supplementary Table 34). Compared to FTND PGS, TUD PGS were more strongly associated across virtually all domains, including TUD (Figure 6a). After conditioning on PGS for other smoking variables (CPD, SmkInit, FTND),
