Additional analyses were conducted to define more clearly the association of the CHRNA4 polymorphisms and the three smoking-related behaviors. First, an association test was performed in the subset of individuals with AIMs data available. The admixture proportion was estimated for each individual and included as a covariate with age and sex in the regression model. The association results remained similar, arguing against stratification as a confounder (Supplementary Table 2). Second, we examined whether recruitment site was a significant confounder by including site as a categorical covariate, and the association results did not change substantially (Supplementary Table 3). Third, haplotype analysis was performed using different SNP combinations but did not yield more significant results (data not shown).