CETP and early-onset autosomal dominant Alzheimer disease: For these reasons, we suggest that drug target MR offers a robust indication of effect direction but may not directly anticipate the effect magnitude of pharmacologically action of a drug on its target, even in the absence of off-target drug compound effects. Findings such as the observed increased risk of AMD (from lower CETP), or of asthma and Alzheimer’s disease (from lower PCSK9), or the apparent protective effect on MS (from lower PCSK9) provide inference on the likely consequences of protein inhibition.