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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

We consider large-scale studies in which thousands of significance tests are performed simultaneously. In some of these studies, the multiple testing procedure can be severely biased by latent confounding factors such as batch effects and…

Methodology · Statistics 2016-06-21 Jingshu Wang , Qingyuan Zhao , Trevor Hastie , Art B. Owen

A new method based on the rejection sampling for finding statistical tests is proposed. This method is conceptually intuitive, easy to implement, and applicable for arbitrary dimension. To illustrate its potential applicability, three…

Methodology · Statistics 2026-03-11 Markku Kuismin

When testing many hypotheses, often we do not have strong expectations about the directions of the effects. In some situations however, the alternative hypotheses are that the parameters lie in a certain direction or interval, and it is in…

Methodology · Statistics 2026-03-02 Jesse Hemerik

The procedure for establishing mediation, i.e., determining that an independent variable X affects a dependent variable Y through some mediator M, has been under debate. The classic causal steps require that a "total effect" be significant,…

Econometrics · Economics 2023-09-26 Tingxuan Han , Luxi Zhang , Xinshu Zhao , Ke Deng

Mediation analysis with contemporaneously observed multiple mediators is an important area of causal inference. Recent approaches for multiple mediators are often based on parametric models and thus may suffer from model misspecification.…

Methodology · Statistics 2022-08-30 Samrat Roy , Michael J. Daniels , Brendan J. Kelly , Jason Roy

We study a large-scale one-sided multiple testing problem in which test statistics follow normal distributions with unit variance, and the goal is to identify signals with positive mean effects. A conventional approach is to compute…

Methodology · Statistics 2026-05-15 Kwangok Seo , Johan Lim , Hyungwon Choi , Jaesik Jeong

During the past few years, mediation analysis has gained increasing popularity across various research fields. The primary objective of mediation analysis is to examine the direct impact of exposure on outcome, as well as the indirect…

Computation · Statistics 2023-05-18 Haixiang Zhang , Xin Li

In this paper, we consider the problem of simultaneously testing many two-sided hypotheses when rejections of null hypotheses are accompanied by claims of the direction of the alternative. The fundamental goal is to construct methods that…

Statistics Theory · Mathematics 2017-03-21 Anjana Grandhi , Wenge Guo , Joseph P. Romano

Mediation analysis extending beyond single mediators has gained significant attention in recent years. However, related methods often assume the absence of unmeasured mediator-outcome confounding. To address this, we develop a mediation…

Methodology · Statistics 2026-03-31 Kang Shuai , Lan Liu , Yangbo He , Wei Li

Mediation analysis aims to identify and estimate the effect of an exposure on an outcome that is mediated through one or more intermediate variables. In the presence of multiple intermediate variables, two pertinent methodological questions…

Quantitative Methods · Quantitative Biology 2026-01-06 Allan Jérolon , Flora Alarcon , Florence Pittion , Magali Richard , Olivier François , Etienne E. Birmelé , Vittorio Perduca

Mediation analyses are a statistical tool for testing the hypothesis about how the relationship between two variables may be direct or indirect via a third variable. Assessing statistical significance has been an area of active research;…

Methodology · Statistics 2021-06-07 Jason Steffener

Large-scale multiple testing is a fundamental problem in high dimensional statistical inference. It is increasingly common that various types of auxiliary information, reflecting the structural relationship among the hypotheses, are…

Methodology · Statistics 2021-10-07 Hongyuan Cao , Jun Chen , Xianyang Zhang

Causal mediation analysis, pleiotropy analysis, and replication analysis are three highly popular genetic study designs. Although these analyses address different scientific questions, the underlying inference problems all involve…

Methodology · Statistics 2023-09-25 Ryan Sun , Zachary McCaw , Xihong Lin

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

We consider statistical procedures for hypothesis testing of real valued functionals of matched pairs with missing values. In order to improve the accuracy of existing methods, we propose a novel multiplication combination procedure.…

Statistics Theory · Mathematics 2018-01-29 Lubna Amro , Frank Konietschke , Markus Pauly

Many psychologists do not realize that exploratory use of the popular multiway analysis of variance (ANOVA) harbors a multiple comparison problem. In the case of two factors, three separate null hypotheses are subject to test (i.e., two…

Mediation analysis is difficult when the number of potential mediators is larger than the sample size. In this paper we propose new inference procedures for the indirect effect in the presence of high-dimensional mediators for linear…

Methodology · Statistics 2019-10-29 Ruixuan Rachel Zhou , Liewei Wang , Sihai Dave Zhao

While multiple testing procedures have been the focus of much statistical research, an important facet of the problem is how to deal with possible confounding. Procedures have been developed by authors in genetics and statistics. In this…

Methodology · Statistics 2008-12-18 Debashis Ghosh

Path-specific effects are a broad class of mediated effects from an exposure to an outcome via one or more causal pathways with respect to some subset of intermediate variables. The majority of the literature concerning estimation of…