The association between these variants and lung cancer constitutes Mendelian randomization evidence on the causal nature of the smoking–lung cancer association (48). In this case, we do not, of course, require such confirmation, but it serves as proof of principle for this approach. These findings also have important implications for epidemiology and genetic association studies, including large GWAS of cigarette smoking behavior, which typically rely on retrospective self-report measures. We discuss these implications below.
