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Alice R Carter, Eleanor C. M. Sanderson, Gemma Hammerton, Rebecca Claire Richmond, George Davey Smith, Jon Heron, Amy E. Taylor, Neil M Davies, Laura D Howe
Mediation analysis seeks to explain the pathway(s) through which an exposure affects an outcome. Traditional, non-instrumental variable methods for mediation analysis experience a number of methodological difficulties, including bias due to confounding between an exposure, mediator and outcome and measurement error. Mendelian randomisation (MR) can be used to improve causal inference for mediation analysis. We describe two approaches that can be used for estimating mediation analysis with MR: multivariable MR (MVMR) and two-step MR. We outline the approaches and provide code to demonstrate how they can be used in mediation analysis. We review issues that can affect analyses, including confounding, measurement error, weak instrument bias, interactions between exposures and mediators and analysis of multiple mediators. Description of the methods is supplemented by simulated and real data examples. Although MR relies on large sample sizes and strong assumptions, such as having strong instruments and no horizontally pleiotropic pathways, our simulations demonstrate that these methods are unaffected by confounders of the exposure or mediator and the outcome and non-differential measurement error of the exposure or mediator. Both MVMR and two-step MR can be implemented in both individual-level MR and summary data MR. MR mediation methods require different assumptions to be made, compared with non-instrumental variable mediation methods. Where these assumptions are more plausible, MR can be used to improve causal inference in mediation analysis.
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Carter, A. R., Sanderson, E. C. M., Hammerton, G., Richmond, R. C., Smith, G. D., Heron, J., Taylor, A. E., Davies, N. M., & Howe, L. D. (2021). Mendelian randomisation for mediation analysis: current methods and challenges for implementation. European Journal of Epidemiology, 36(5), 465–478. https://doi.org/10.1007/s10654-021-00757-1
Carter, Alice R, et al. "Mendelian randomisation for mediation analysis: current methods and challenges for implementation." European Journal of Epidemiology, vol. 36, no. 5, 2021, pp. 465–478, https://doi.org/10.1007/s10654-021-00757-1.
Carter, Alice R, Eleanor C. M. Sanderson, Gemma Hammerton, Rebecca Claire Richmond, George Davey Smith, Jon Heron, Amy E. Taylor, Neil M Davies, and Laura D Howe. "Mendelian randomisation for mediation analysis: current methods and challenges for implementation." European Journal of Epidemiology 36, no. 5 (2021): 465–478. https://doi.org/10.1007/s10654-021-00757-1.
Carter A. R., Sanderson E. C. M., Hammerton G. [и др.] Mendelian randomisation for mediation analysis: current methods and challenges for implementation // European Journal of Epidemiology. — 2021. — Vol. 36, № 5. — P. 465–478. — URL: https://doi.org/10.1007/s10654-021-00757-1
@article{carter2021mendelian,
title = {{Mendelian randomisation for mediation analysis: current methods and challenges for implementation}},
author = {Alice R Carter and Eleanor C. M. Sanderson and Gemma Hammerton and Rebecca Claire Richmond and George Davey Smith and Jon Heron and Amy E. Taylor and Neil M Davies and Laura D Howe},
journal = {European Journal of Epidemiology},
year = {2021},
volume = {36},
number = {5},
pages = {465--478},
doi = {10.1007/s10654-021-00757-1},
url = {https://doi.org/10.1007/s10654-021-00757-1}
}TY - JOUR AU - Carter, Alice R AU - Sanderson, Eleanor C. M. AU - Hammerton, Gemma AU - Richmond, Rebecca Claire AU - Smith, George Davey AU - Heron, Jon AU - Taylor, Amy E. AU - Davies, Neil M AU - Howe, Laura D TI - Mendelian randomisation for mediation analysis: current methods and challenges for implementation JO - European Journal of Epidemiology VL - 36 IS - 5 SP - 465 EP - 478 PY - 2021 DA - 2021/05/01 DO - 10.1007/s10654-021-00757-1 UR - https://doi.org/10.1007/s10654-021-00757-1 ER -
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