Recent studies examining instruments based on specific genes that mimic the effects of lipid-modifying therapies, such as PCSK9, HMGCR, and NPC1L1, have shown weaker effects on IS than on CHD, but also suggest that the different pathways involved may affect stroke subtypes differentially.15,37,38 A study of the combined effects of CETP and HMGCR has also suggested that the benefits of lowering LDL-C may depend on the reduction in apoB-containing lipoprotein particles.39 This evidence concerns the gene PCSK9 and coronary artery disorder.