We conducted single variant and gene-based tests of association with five smoking and drinking phenotypes. We applied a novel fine mapping analysis to prioritize causal variants using statistical and functional information. We also evaluated the contribution of rare exonic variants to the heritability of these phenotypes. Family studies, as well as studies of the aggregate effects of common variants, have found both alcohol use and tobacco use to be heritable behaviors(30, 34–38). Research on the aggregate contribution of rare variants, however, has been scarce, with previous work on related phenotypes in smaller samples failing to detect aggregate effects for smoking and alcohol consumption(28). We used meta-analytic summary statistics to quantify the contribution to heritability of variants in various functional categories and frequency bins.
