Fig. 5: An applied example of the translational framework to replicate the LDL-C-lowering therapeutic targets encoded by APOB, LDLR, and LPA loci on coronary artery disease (CAD).
From: A translational framework of genoproteomic studies for cardiovascular drug discovery
1a The scatter plot of genetic effects on LDL-C and CAD using all available genetic variants at genome-wide significance across the genome. 2a The scatter plot of genetic effects on LDL-C and CAD using all available variants within or near either APOB, LDLR, or LPA loci as instrumental variables (IVs). 2b The possible pleiotropic effects detected using Genome-wide mR Analysis under Pervasive PLEitropy (GRAPPLE). 2c Forest plot of the genetically mimicked LDL-C-lowering effects driven by APOB, LDLR, and LPA loci on CAD using cis-pQTLs or fine-mapped variants as IVs in Mendelian randomization analyses. 2d–f: Regional plots of colocalization analyses for APOB, LDLR, LPA loci, and expression quantitative trait loci from eQTLGen phase 1 and CAD. 3a–c Volcano plots of the potential side effects of LDL-C-lowering driven by APOB, LDLR, and LPA loci. 4a The observed and g-formula estimated cumulative atherosclerotic cardiovascular disease (ASCVD) risk based on the Chinese Multi-provincial Cohort Study participants. 4b–d: The estimated cumulative ASCVD, CVD, and all-cause mortality risk with or without hypothetical interventions on lowering LDL-C by modifying APOB, LDLR, and LPA.
