Chapter 6:

In this chapter, we consider the interpretation of causal effects assessed and estimated in Mendelian randomization, and address the question of under what circumstances a Mendelian randomization estimate may be a reliable guide to the effect of an intervention on the exposure of interest in practice.

In Mendelian randomization, differences in the exposure distribution due to genetic variation are materially distinct from the change due to any proposed therapeutic intervention on the exposure, and so may affect the outcome differently. Consequently, it may be misleading to interpret the magnitude of a Mendelian randomization estimate as the expected impact of an intervention on the exposure in practice. Awareness of this is important for the use of Mendelian randomization in target-based drug development.