The IV assumptions are illustrated in Figure 1. IV1 is the only assumption that can be fully empirically tested, because IV2 and IV3 depend on all possible confounders of the exposure—outcome association, both measured and unmeasured. Any statistical method for obtaining causal inferences must by necessity make an untestable assumption. The validity of a causal conclusion from a Mendelian randomization analysis depends on the plausibility of these assumptions.
