We were unable to directly assess more refined phenotypes and highly heritable traits such as nicotine metabolism,58 given our reliance on existing data originally collected for other purposes. Moreover, we were unable to examine gene × environment interactions using meta-GWAS analytic approach. Our analyses did not incorporate environmental covariate analyses, such as type of cigarettes smoked, mentholated or non-mentholated, dietary factors, socioeconomic status and other factors that might influence one or more of the phenotypes analyzed—data were not uniformly available and beyond the scope of the planned analyses we undertook in this discovery investigation. Future prospective studies with more detailed characterizations of smoking phenotypes and relevant environmental covariates are needed to identify additional variants that may be associated with smoking behaviors.
