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Nat. Rev. Cardiol. doi:10.1038/nrcardio.2017.78 Figure 4 Mendelian randomization (MR) using a variant that disrupts normal function of the exposure Figure 4 | Mendelian randomization (MR) using a variant that disrupts normal function of the exposure. a | Reduced hepatic uptake of HDL particles through the scavenger receptors leads to the accumulation of circulating HDL cholesterol (HDL-C) and increased risk of coronary heart disease (CHD). However, this observation does not indicate that HDL-C is harmful, but provides some support for the notion that appropriate function of reverse cholesterol transport might be beneficial to cardiovascular health. b | A variant in IL6R leads to reduced membrane-bound IL-6, which in turn results in increased levels of circulating IL-6, disruption of classical IL-6 signalling, reduced C-reactive protein (CRP) levels, and a reduction in risk of CHD. These figures are schematic representations and should not be interpreted as formal directed acyclic graphs. Holmes, M. V. et al. (2017) Mendelian randomization in cardiometabolic disease: challenges in evaluating causality Nat. Rev. Cardiol. doi:10.1038/nrcardio.2017.78