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Cold Spring Harbor Perspectives in Medicine
Article . 2020 . Peer-reviewed
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Multivariable Mendelian Randomization and Mediation

Authors: Sanderson, Eleanor C M;

Multivariable Mendelian Randomization and Mediation

Abstract

Mendelian randomization (MR) is the use of genetic variants associated with an exposure to estimate the causal effect of that exposure on an outcome. Mediation analysis is the method of decomposing the effects of an exposure on an outcome, which act directly, and those that act via mediating variables. These effects are decomposed through the use of multivariable analysis to estimate the causal effects between three types of variables: exposures, mediators, and an outcome. Multivariable MR (MVMR) is a recent extension to MR that uses genetic variants associated with multiple, potentially related exposures to estimate the effect of each exposure on a single outcome. MVMR allows for equivalent analysis to mediation within the MR framework and therefore can also be used to estimate mediation effects. This approach retains the benefits of using genetic instruments for causal inference, such as avoiding bias due to confounding, while allowing for estimation of the different effects required for mediation analysis. This review explains MVMR, what is estimated when one exposure is a mediator of another in an MVMR estimation, and how MR and MVMR can therefore be used to estimate mediated effects. This review then goes on to consider the advantages and limitations of using MR and MVMR to conduct mediation analysis.

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Keywords

Causality, Mediation Analysis, 330, 610, Genetic Variation, Humans, Mendelian Randomization Analysis

  • BIP!
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    selected citations
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    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    617
    popularity
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    Top 0.1%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Top 1%
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    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
617
Top 0.1%
Top 1%
Top 0.1%
Green
bronze