1. Figure 1 Mendelian randomization study
assessing the relationship between BMI and coronary heart disease
Figure 1 | Mendelian randomization study assessing the relationship between BMI and coronary heart disease. The validity of Mendelian randomization analyses for assigning causal relationships is based on three assumptions. With respect to the paper by Lyall et al., the first assumption is that genetic variables, namely the single-nucleotide polymorphisms (SNPs) associated with BMI, are robustly associated with BMI; the second is that genetic variables are not directly associated with any confounders affecting the relationship between BMI and the outcomes of type 2 diabetes mellitus (T2DM) and coronary heart disease (CHD); and the third assumption is that genetic variables only effect progression to T2DM or CHD through their association with BMI. The violation of any one of these three assumptions could result in biased estimates of effects. In addition, if T2DM directly effects progression to CHD, the model would also be invalidated. Relationships indicated by the blue arrows satisfy the model's assumptions; relationships indicated by the red arrows invalidate the use of Mendelian randomization to implicate causal relationships between BMI and the outcomes of T2DM and CHD.
Aslibekyan, S. & Garvey, W. T. (2017) Obesity and cardiometabolic disease — more than meets the eye
Nat. Rev. Endocrinol. doi: /nrendo