Fig 1. A schematic representation of the drug-target MR approach undertaken in this study using, for instance, HMGCR variants to proxy for HMG-CoA reductase inhibition (the mechanism of action of statin therapy) to estimate its genetically predicted effect on CAD.

Genetic variants robustly associated with a lipoprotein lipid trait (for instance, LDL cholesterol) based on P < 1 × 10⁻⁶ within 100 kbs of encoding genes were identified as genetic proxies for perturbing therapeutic targets. A sensitivity analysis restricted to 50 kbs on either side of encoding genes was also undertaken in this study. CAD, coronary artery disease; kbs, kilobases; LDL, low-density lipoprotein; MR, mendelian randomisation.