PGSs were calculated using PRS-Continuous shrinkage software (PRS-CS).114 We used the default setting in PRS-CS to estimate the shrinkage parameters and fixed the random seed to 1 for reproducibility. To identify associations between the PGS for TUD and clinical phenotypes, we performed a PheWAS by fitting logistic regression models for binary phenotypes and linear regression models for continuous phenotypes. Analyses were conducted using the PheWAS v0.12 R package115 adjusting for sex, median age and the first ten PCs within each genetic ancestry. We performed sensitivity analyses by covarying for SmkInit, CPD13 and FTND27 PGS. Bonferroni correction was applied for each ancestral-specific analysis to account for multiple testing (p<7.25E-05).
