Mendelian randomization uses genetic variants to make causal inferences about a modifiable exposure. Subject to a genetic variant satisfying the instrumental variable assumptions, an association between the variant and outcome implies a causal effect of the exposure on the outcome. Complications arise with a binary exposure that is a dichotomization of a continuous risk factor (for example, hypertension is a dichotomization of blood pressure). This can lead to violation of the exclusion restriction assumption: the genetic variant can influence the outcome via the continuous risk factor even if the binary exposure does not change. Provided the instrumental variable assumptions are satisfied for the underlying continuous risk factor, causal inferences for the binary exposure are valid for the continuous risk factor. Causal estimates for the binary exposure assume the causal effect is a stepwise function at the point of dichotomization. Even then, estimation requires further parametric assu
