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. 2023 Mar 28;11:1022367. doi: 10.3389/fpubh.2023.1022367

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Copyright © 2023 Zhang, Yang, Zhang, Yin, Man and Lu.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Directed acyclic graph of the MR mediation analysis. The total effect of exposure on the outcome, βc, was derived using univariable MR (i.e., genetically predicted EduYears as exposure and EC as outcome). The total effect was decomposed into (i) indirect effect (mediation effect) using a two-step approach (where βa is the effect of EduYears on BMI, and βb is the effect of BMI on EC adjusting for EduYears) and the product method (βa * βb) and (ii) direct effect (βc′ = βc – βa*βb). The same process is applied to obtain the individual mediation effect of each mediator. We divided the individual mediated effect by the total effect to estimate the individual proportion mediated. The combined mediation effect is calculated by accumulating each mediation effect under multivariable MR of multiple parallel mediation analyses. We divided the combined mediated effect by the total effect to estimate the total proportion mediated.