Seventeen independent studies (see Table S1) with smoking and drinking phenotypes were included in the discovery phase. Individual studies conducted association analysis accounting for age, sex, any study-specific covariates, and ancestry principal components (see Table S2 for genomic controls), and submitted summary statistics for meta-analysis. For studies with related individuals (see Table S1), relatedness was accounted for in linear mixed models using empirically estimated kinships from common SNPs(43). Residuals were inverse-normalized to help ensure well-behaved test statistics for rare variant tests.
