Correlated epidemiological and genetic factors can be causally dissected with Mendelian randomization.GRS = genetic risk scores from independent genome-wide significant SNPs. BMI = body mass index, LDL-C = LDL cholesterol, HDL-C = HDL cholesterol, CHD = coronary heart disease. A) Epidemiological factors from FINRISK and their associations with risk of CHD after all evaluated factors have been normalized, and age and sex have been regressed out. Test statistics for each of the panel comparisons are written in plot corners and are as follows (t-tests for the top 3 panels, ANOVA for the bottom 3 panels): BMI: p=3.5e-18; LDL: p=0.79; HDL: p=5.3e-62; LDL and BMI: p=2.7e-73, HDL and BMI: p<1e-100, HDL and LDL: p=2.0e-7. B) Genetic factors associated with LDL-C, HDL-C, and BMI enable causal inference for CHD. Whereas genetic risk of increased LDL-C and BMI are causally associated with increased risk of CHD, HDL-C is genetically anti-correlated with CHD but is not causal. Genetic correlations (ρg) are from LD Hub (12).
