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Figure 4 | Emerging Themes in Epidemiology

Figure 4

From: Can we apply the Mendelian randomization methodology without considering epigenetic effects?

Figure 4

Epigenetic effect present due to inherited altered gene expression (βXG + βEG = βXG*). Compared to Figure 3, when epigenetic effect is present, the core assumptions of MR are violated. Let E denote an environmental factor, which interacts with G at the maternal level. In the presence of this interaction, G and E × G are clearly dependent. Thus, the association between G and X is affected by the E × G interaction term. This violates core assumptions (a) and (b) above. Thus, Mendelian Randomization should be applied with caution if the possibility of epigenetic effects exists. Further, as shown in Analysis section, βXG* = βXG+ βEG and βITT = βXGIV'. Therefore, βITT ≠ βXGβIV'. Thus, when Mendelian Randomization is violated, there is a tendency to contravene the stated relationship between βITT, βXG, and βIV as given by equation (5). From the randomized controlled trial analogy, βITT is the intention-to-treat effect; βIV(biologic effect of received treatment); and βXG (the effect of G on X).

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