The estimated total SNP heritability for AgeSmk, CigDay, PckYr, SmkInit, and DrnkWk was 6%, 9%, 10%, 14% and 16%. Significant phenotypic variance was explained by rare nonsynonymous variants for all traits, ranging from 1.0%−2.2% (Table 3). As a fraction of the SNP heritability, rare nonsynonymous variants accounted for 11%−18%. Results for all seven functional categories are listed in Table S8; appreciable heritability was accounted for by common and rare coding variants, and intergenic variants. Variants in the untranslated regions and intronic regions contributed less. Almost all pairs of phenotypes were genetically correlated (Table 4, Panel A), and the direction of the genetic correlations were in the expected direction. For instance, CigDay was positively correlated with DrnkWk (0.2 ± 0.09), consistent with the observation that increased alcohol consumption is correlated with increased tobacco consumption. Age of initiation has a negative correlation with all other traits, which is consistent with the observation that an earlier age of smoking initiation is correlated with increased tobacco and alcohol consumption in adulthood. The patterns and magnitudes of correlation are highly similar when considering only rare nonsynonymous variants (Table 4, Panel B).
