1. Figure 3 Mendelian randomization (MR) using a genetic
variant that associates with multiple biomarkers on separate pathways
Figure 3 | Mendelian randomization (MR) using a genetic variant that associates with multiple biomarkers on separate pathways. a | Using single nucleotide polymorphisms (SNPs) in PPM1K (which encodes a mitochondrial phosphatase that activates branched-chain α-keto acid dehydrogenase [BCKD], responsible for the rate-limiting step of metabolism of the branched-chain amino acids) to infer causality of three separate amino acids yields an erroneous conclusion, as this inference ascribes a causal estimate to each amino acid from the same PPM1K–diabetes association that is scaled to the PPM1K–amino acid estimate (Table 2). The three amino acids are initially catabolized prior to the enzymatic action of BCKD. b | Using SNPs in APOE to infer causality of C-reactive protein (CRP) yields an erroneous conclusion, as the SNP is pleiotropic for CRP and LDL cholesterol (LDL-C). These figures are schematic representations and should not be interpreted as formal directed acyclic graphs. CHD, coronary heart disease.
Holmes, M. V. et al. (2017) Mendelian randomization in cardiometabolic disease: challenges in evaluating causality
Nat. Rev. Cardiol. doi: /nrcardio