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In response to the unique challenge created by high-dimensional mediators in mediation analysis, this paper presents a novel procedure for testing the nullity of the mediation effect in the presence of high-dimensional mediators. The…

Methodology · Statistics 2025-05-28 Yinan Lin , Zijian Guo , Baoluo Sun , Zhenhua Lin

Identifying individual mediators is a central goal of high-dimensional mediation analysis, yet pervasive dependence among mediators can invalidate standard debiased inference and lead to substantial false discovery rate (FDR) inflation. We…

Methodology · Statistics 2026-02-19 Chen Shi , Zhao Chen , Christina Dan Wang

Mediation hypothesis testing for a large number of mediators is challenging due to the composite structure of the null hypothesis, H0:alpha*beta=0 (alpha: effect of the exposure on the mediator after adjusting for confounders; beta: effect…

Methodology · Statistics 2022-03-28 Jiacong Du , Xiang Zhou , Wei Hao , Yongmei Liu , Jennifer A. Smith , Bhramar Mukherjee

There is a challenge in selecting high-dimensional mediators when the mediators have complex correlation structures and interactions. In this work, we frame the high-dimensional mediator selection problem into a series of hypothesis tests…

Methodology · Statistics 2025-09-16 Runqiu Wang , Ran Dai , Jieqiong Wang , Kah Meng Soh , Ziyang Xu , Mohamed Azzam , Hongying Dai , Cheng Zheng

Mediation analysis has become an important tool in the behavioral sciences for investigating the role of intermediate variables that lie in the path between a randomized treatment and an outcome variable. The influence of the intermediate…

This paper studies the high-dimensional mixed linear regression (MLR) where the output variable comes from one of the two linear regression models with an unknown mixing proportion and an unknown covariance structure of the random…

Methodology · Statistics 2020-11-10 Linjun Zhang , Rong Ma , T. Tony Cai , Hongzhe Li

Mediation analysis plays a crucial role in causal inference as it can investigate the pathways through which treatment influences outcome. Most existing mediation analysis assumes that mediation effects are static and homogeneous within…

Methodology · Statistics 2026-03-02 Yijiao Zhang , Yubai Yuan , Yuexia Zhang , Zhongyi Zhu , Annie Qu

Identifying signals that replicate across multiple studies is essential for establishing robust scientific evidence, yet existing methods for high-dimensional replicability analysis either rely on restrictive modeling assumptions, are…

Methodology · Statistics 2026-03-05 Haochen Lei , Yan Li , Hongyuan Cao

We study high-dimensional mediation analysis in which exposures, mediators, and outcomes are all multivariate, and both exposures and mediators may be high-dimensional. We formalize this as a many (exposures)-to-many (mediators)-to-many…

Mediation analysis is becoming an increasingly important tool in scientific studies. A central question in high-dimensional mediation analysis is to infer the significance of individual mediators. The main challenge is the sheer number of…

Methodology · Statistics 2021-02-23 Chengchun Shi , Lexin Li

In many scenarios such as genome-wide association studies where dependences between variables commonly exist, it is often of interest to infer the interaction effects in the model. However, testing pairwise interactions among millions of…

Methodology · Statistics 2022-09-02 Jingyi Duan , Yang Ning , Xi Chen , Yong Chen

Mediation analysis seeks to identify and quantify the paths by which an exposure affects an outcome. Intermediate variables which are effected by the exposure and which effect the outcome are known as mediators. There exists extensive work…

Methodology · Statistics 2020-11-13 James P. Long , Ehsan Irajizad , James D. Doecke , Kim-Anh Do , Min Jin Ha

Social and behavioral scientists are increasingly employing technologies such as fMRI, smartphones, and gene sequencing, which yield 'high-dimensional' datasets with more columns than rows. There is increasing interest, but little…

Methodology · Statistics 2019-10-11 Erik-Jan van Kesteren , Daniel L. Oberski

In many applications, the process of identifying a specific feature of interest often involves testing multiple hypotheses for their joint statistical significance. Examples include mediation analysis which simultaneously examines the…

Methodology · Statistics 2023-05-30 Linsui Deng , Kejun He , Xianyang Zhang

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 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

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

It is of substantial scientific interest to detect mediators that lie in the causal pathway from an exposure to a survival outcome. However, with high-dimensional mediators, as often encountered in modern genomic data settings, there is a…

Methodology · Statistics 2024-08-14 Tzu-Jung Huang , Zhonghua Liu , Ian W. McKeague

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

Mediation analysis is an important statistical tool in many research fields, where the joint significance test is widely utilized for examining mediation effects. Nevertheless, the limitation of this mediation testing method stems from its…

Methodology · Statistics 2024-09-06 Haixiang Zhang
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