Panel A shows associations with cardio-metabolic disease outcomes of the ANGPTL4 p.Glu40Lys loss-of-function allele in the UK Biobank, EPIC-Norfolk and EPIC-InterAct studies. Associations are scaled to represent the odds ratio per standard deviation genetically-lower triglyceride levels. Data are from the UK Biobank, EPIC-Norfolk and EPIC-InterAct studies. Abbreviations: OR, odds ratio; CI, confidence interval; LDL-C, low-density lipoprotein cholesterol; SD, standard deviation. Panel B shows associations with protection against coronary disease for different genetic exposures associated with lower LDL-C levels. A clear log-linear relationship between genetic-difference in LDL-C and association with lower risk is observed for several mechanisms, while ANGPTL3 loss-of-function variants are outliers in this relationship. The graphs display the % lower risk for coronary disease (log scale) and the difference in standard deviations of genetically-lower LDL-C. For individual variants the estimates represent per-allele differences; for quintiles of the LDL-C score the difference compared to the bottom quintile; for the overall genetic score the difference per standard deviation genetically-lower LDL-C; for ANGPTL3 variants the difference in carriers compared to non-carriers. Abbreviations: Q, quintile; SD, standard deviation; LDL-C, low-density lipoprotein cholesterol.