Skip to main content
. 2019 Jan 29;321(4):364–373. doi: 10.1001/jama.2018.20045

Figure 2. Association of Genetic Variants and Genetics Scores With Triglycerides, Low-Density Lipoprotein Cholesterol (LDL-C), and Risk of Coronary Heart Disease (CHD) per 10-mg/dL Lower Concentration of Apolipoprotein B (ApoB)–Containing Lipoproteins.

Figure 2.

The figure shows the associations with triglycerides, LDL-C, and risk of CHD for the same 10-mg/dL lower ApoB-containing lipoprotein concentration for variants in the LPL and LDLR scores as compared with variants in the genes that encode the targets of current therapies that lower LDL-C through the LDL receptor pathway; variants in the genes that encode the targets of potential therapies that lower triglycerides through the LPL pathway; and variants in the APOB gene. For example, each 10-mg/dL lower plasma ApoB concentration associated with the partial loss-of-function rs11591147 variant in the PCSK9 gene was associated with a corresponding 18.0-mg/dL lower LDL-C level, no change in triglycerides, and a lower risk of CHD (odds ratio, 0.774 [95% CI, 0.721-0.832]). By contrast, for the same 10-mg/dL lower plasma ApoB concentration associated with the functional rs116843064 variant in the ANGPTL4 gene, there was a corresponding 69.4-mg/dL lower triglyceride level, no change in LDL-C, and a similar lower risk of CHD (odds ratio, 0.726 [95% CI, 0.609-0.865]). Furthermore, for the same 10-mg/dL lower plasma ApoB concentration associated with variants in the APOB gene score, there was a corresponding 9.7-mg/dL lower triglyceride level, 15.6-mg/dL lower LDL-C level, and a similar lower risk of CHD (odds ratio, 0.778 [95% CI, 0.737-0.821]). Despite a range of associated changes in triglycerides, LDL-C, or both, all genetic variants and genetic scores were associated with similar lower risk of CHD for the same 10-mg/dL lower plasma ApoB concentration. The APOB score is composed of the 8 independently inherited variants in the APOB gene listed in the figure. Boxes represent effect size estimates and lines represent 95% CIs. Associations with CHD per 10-mg/dL lower ApoB were measured in all 654 783 participants included in the study; associations with changes in triglycerides and LDL-C per 10-mg/dL lower ApoB were measured in up to 305 699 participants from the Global Lipid Genetics Consortium.