Research Paper Volume 15, Issue 24 pp 15228—15242

Figure 1. Flowchart of the study design and MR assumptions. Assumptions of the Mendelian randomization study: in this study, genetic instruments were selected to represent the pharmacological modulation of drug target proteins based on their associations with circulating lipid concentrations (relevance assumption). Additionally, it was assumed that the selected genetic variants are not associated with confounding factors (independence assumption). The third assumption was that genetic variants should not affect human lifespan through other pathways (exclusion restriction assumption). Abbreviations: LDL-C, Low-Density Lipoprotein Cholesterol; TC, Total cholesterol; TG, Total triglyceride; LDLR, Low-Density Lipoprotein Receptor; HMGCR, 3-hydroxy-3-methylglutaryl coenzyme A reductase; PCKS9, Proprotein Convertase Subtilisin/Kexin Type 9; NPC1L1, Niemann-Pick C1-like 1; APOB, Apoprotein B-100; CETP, Cholesteryl Ester Transfer Protein; LPL, Lipoprotein Lipase; ANGPTL3, Angiopoietin-related protein 3; APOC3, Apoprotein C-III; CHD, Major coronary heart disease; CAS, Coronary atherosclerosis; T2D, Type 2 diabetes.