Polygenic risk scores were computed using LDpred for each ancestry group separately, an approach that incorporates the correlation between genetic variants to re-weight effect size estimates63. We used an independent prediction cohort, Add Health35, to validate each score. Add Health is a nationally representative sample of US adolescents enrolled in grades 7 through 12 during the 1994–1995 school year. The mean birth year of respondents was 1979 (s.d. = 1.8) and the mean age at assessment (here, wave 4) was 29.0 years (s.d. = 1.8), which is comparable, in general, to the age of participants in the 23andMe cohort but younger, on average, than those in other cohorts. Add Health is composed of individuals from the same four major ancestral groups (defined with reference to 1000 Genomes; see Supplementary Note for details) comprising our ancestry-stratified results (EUR, AFR, AMR and EAS). Phenotypic descriptive statistics are given in Supplementary Table 12. Across the full Add Health sample, approximately 41% ever smoke regularly and reported an average of 7.3 cigarettes per day. For each polygenic score, we used only HapMap3 variants and
