TY - JOUR
T1 - Multivariable Mendelian Randomization and Mediation
AU - Sanderson, Eleanor C M
N1 - The acceptance date for this record is provisional and based upon the month of publication for the article.
PY - 2020/4/27
Y1 - 2020/4/27
N2 - 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.
AB - 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.
U2 - 10.1101/cshperspect.a038984
DO - 10.1101/cshperspect.a038984
M3 - Review article (Academic Journal)
C2 - 32341063
JO - Cold Spring Harbor perspectives in medicine
JF - Cold Spring Harbor perspectives in medicine
SN - 2157-1422
ER -