One assumption that we have made in this paper is that of no causal effect heterogeneity. This means that the same change in the outcome is expected no matter how the exposure is intervened on, and so the same causal effect is identified by different genetic variants that are valid IVs. In practice, it may be that genetic variants influence the exposure via different biological mechanisms. However, empirical evidence for the causal effect of LDL‐c on CAD risk provides no evidence of causal effect heterogeneity despite genetic variants having different mechanisms and substantially different magnitudes of association with LDL‐c (Davey Smith and Hemani, 2014).
