Smoking and alcohol use rates are influenced by secular trends and policy changes over the last half century. We therefore selected two independent prediction cohorts, the Health and Retirement Study (HRS)21 and the National Longitudinal Study of Adolescent to Adult Health (Add Health)20. The HRS is a nationally representative study of U.S. households that began in 1992; the mean birth year of respondents is 1938 (SD=9.3), and the mean age at the time of assessment is 57.6 (SD=8.9). Add Health is a nationally representative sample of U.S. adolescents enrolled in grades 7 through 12 during the 1994–1995 school year. The mean birth year of respondents was 1979 (SD=1.8), and the mean age at assessment (here, wave 4) was 29.0 (SD=1.8). In the HRS, ~57% of respondents reported ever smoking regularly, and these respondents smoked ~13 cigarettes per day. In Add Health, slightly fewer (~53%) of respondents reported ever smoking regularly, and these respondents smoked ~11 cigarettes per day on average (Supplementary Table 14). For each of our five phenotype scores, we used variants that overlapped with HapMap3 (~1.1 million) to
