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Greater understanding of the pathways through which an environmental mixture operates is important to design effective interventions. We present new methodology to estimate natural direct and indirect effects and controlled direct effects…

To investigate causal mechanisms, causal mediation analysis decomposes the total treatment effect into the natural direct and indirect effects. This paper examines the estimation of the direct and indirect effects in a general treatment…

Statistics Theory · Mathematics 2024-01-24 Lukang Huang , Wei Huang , Oliver Linton , Zheng Zhang

The paper considers mediation analysis with longitudinal data under latent growth curve models within a counterfactual framework. Estimators and their standard errors are derived for natural direct and indirect effects when the mediator,…

Methodology · Statistics 2021-03-11 Adam J. Sullivan , Douglas D. Gunzler , Nathan Morris , Tyler J. VanderWeele

The goal of causal mediation analysis, often described within the potential outcomes framework, is to decompose the effect of an exposure on an outcome of interest along different causal pathways. Using the assumption of sequential…

Methodology · Statistics 2021-11-09 Lexi Rene , Antonio R. Linero , Elizabeth Slate

Mediation analysis in causal inference has traditionally focused on binary exposures and deterministic interventions, and a decomposition of the average treatment effect in terms of direct and indirect effects. In this paper we present an…

Methodology · Statistics 2020-11-17 Iván Díaz , Nima Hejazi

Mediation analysis in causal inference typically concentrates on one binary exposure, using deterministic interventions to split the average treatment effect into direct and indirect effects through a single mediator. Yet, real-world…

Methodology · Statistics 2023-07-07 David B. McCoy , Alan E. Hubbard , Mark van der Laan , Alejandro Schuler

Decomposing a total causal effect into natural direct and indirect effects is central to revealing causal mechanisms. Conventional methods achieve the decomposition by specifying an outcome model as a linear function of the treatment, the…

Methodology · Statistics 2025-06-05 Guanglei Hong

Causal mediation analysis can improve understanding of the mechanisms underlying epidemiologic associations. However, the utility of natural direct and indirect effect estimation has been limited by the assumption of no confounder of the…

Applications · Statistics 2020-06-16 Kara E. Rudolph , Oleg Sofrygin , Wenjing Zheng , Mark J. van der Laan

Mediation analysis is a strategy for understanding the mechanisms by which treatments or interventions affect later outcomes. Mediation analysis is frequently applied in randomized trial settings, but typically assumes: a) that randomized…

Methodology · Statistics 2021-12-30 Kara E. Rudolph , Nicholas Williams , Ivan Diaz

Causal mediation analysis has historically been limited in two important ways: (i) a focus has traditionally been placed on binary treatments and static interventions, and (ii) direct and indirect effect decompositions have been pursued…

Methodology · Statistics 2022-01-13 Nima S. Hejazi , Kara E. Rudolph , Mark J. van der Laan , Iván Díaz

Causal mediation analysis concerns the pathways through which a treatment affects an outcome. While most of the mediation literature focuses on settings with a single mediator, a flourishing line of research has examined settings involving…

Methodology · Statistics 2021-11-12 Xiang Zhou

In genome-wide epigenetic studies, exposures (e.g., Single Nucleotide Polymorphisms) affect outcomes (e.g., gene expression) through intermediate variables such as DNA methylation. Mediation analysis offers a way to study these intermediate…

Methodology · Statistics 2025-12-08 Asmita Roy , Xianyang Zhang

We consider mediated effects of an exposure, X on an outcome, Y, via a mediator, M, under no unmeasured confounding assumptions in the setting where models for the conditional expectation of the mediator and outcome are partially linear. We…

Methodology · Statistics 2025-01-08 Oliver Hines , Stijn Vansteelandt , Karla Diaz-Ordaz

Mediation analysis breaks down the causal effect of a treatment on an outcome into an indirect effect, acting through a third group of variables called mediators, and a direct effect, operating through other mechanisms. Mediation analysis…

Applications · Statistics 2025-05-13 Judith Abécassis , Houssam Zenati , Sami Boumaïza , Julie Josse , Bertrand Thirion

Causal mediation analysis is an important statistical method in social and medical studies, as it can provide insights about why an intervention works and inform the development of future interventions. Currently, most causal mediation…

Methodology · Statistics 2016-01-26 Cheng Zheng , David C. Atkins , Melissa A. Lewis , Xiao-Hua Zhou

We propose semi- and non-parametric methods to estimate conditional interventional effects in the setting of two discrete mediators whose causal ordering is unknown. Average interventional indirect effects have been shown to decompose an…

Methodology · Statistics 2023-04-19 Max Rubinstein , Zach Branson , Edward H. Kennedy

High-dimensional mediation analysis aims to identify mediating pathways and to estimate indirect effects linking an exposure to an outcome. In this paper, we propose a Bayesian framework to address key challenges in these analyses,…

Methodology · Statistics 2026-02-13 Youngho Bae , Chanmin Kim , Fenglei Wang , Qi Sun , Kyu Ha Lee

This study introduces a mediation analysis framework when the mediator is a graph. A Gaussian covariance graph model is assumed for graph representation. Causal estimands and assumptions are discussed under this representation. With a…

Methodology · Statistics 2023-07-11 Yixi Xu , Yi Zhao

In interventional health studies, causal mediation analysis can be employed to investigate mechanisms through which the intervention affects the targeted health outcome. Identifying direct and indirect (i.e. mediated) effects from empirical…

Causal indirect and direct effects provide an interpretable method for decomposing the total effect of an exposure on an outcome into the effect through a mediator and the effect through all other pathways. When the mediator is a biomarker,…

Methodology · Statistics 2021-08-02 Ariel Chernofsky , Ronald J. Bosch , Judith J. Lok