We next extended the analyses to a deeply characterized sample recruited for genetic studies of substance use disorders: the Yale-Penn sample.47 We examined the association between PGS for TUD and hundreds of other traits derived from a comprehensive psychiatric interview, the Semi-Structured Assessment for Drug Dependence and Alcoholism (SSADDA). TUD-EUR and TUD-AA PGS were strongly associated with nicotine dependence as defined via a Diagnostic and Statistical Manual of Mental Disorders (DSM) diagnosis in both the EUR (OR=1.83, p=3.51E-49; Figure 6b; Supplementary Table 36) and AA cohorts (OR=1.13, p=7.13E-04), respectively, although the latter association did not survive multiple testing correction (Supplementary Table 37). In the EUR cohort, we also noted significant associations between TUD-EUR PGS and 224 other phenotypes, including 163 in the substance-related domain (44 opioid-related, 31 cocaine-related, 25 alcohol-related, 23 tobacco-related, 14 sedative-related, 13 cannabis-related, 10 other, 2 stimulant-related), and 50 in other domains (13 medical, 33 psychiatric [9 PTSD, 11 depression, 7 antisocial personality, 3 suicide, 2 ADHD, and 2 conduct disorder], 9 environmental, and 6 demographic phenotypes. Again, compared to FTND PGS, TUD-EUR PGS was more strongly
