et al., 2014; Wium-Andersen et al., 2015). Furthermore, any instrument for smoking heaviness requires stratifying samples into smokers and non-smokers. Stratification is not possible using the most common MR method, two-sample MR. In two-sample MR, single-nucleotide polymorphism (SNP)-exposure and SNP-outcome effects are estimated in two independent samples and the effect sizes are obtained from GWAS summary statistics. Therefore, in this context stratification is not possible because GWAS summary data do not provide individual level data regarding smoking status.
