Fig. 1

Directed acyclic graphs for Mendelian randomization analyses of (A) total lifetime exposure to tobacco smoke and (B) reported number of cigarettes smoked per day with outcome measures. Observed variables are denoted using squares, unobserved variables are denoted using circles, causal effects have arrows. Dashed lines represent non-causal associations. X: total lifetime exposure to tobacco smoke, X₂: reported number of cigarettes smoked per day, a genetic variant (Z), outcome (Y), and an unobserved confounder (U).