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It becomes increasingly popular to perform mediation analysis for complex data from sophisticated experimental studies. In this paper, we present Granger Mediation Analysis (GMA), a new framework for causal mediation analysis of multiple…

Methodology · Statistics 2017-09-18 Yi Zhao , Xi Luo

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…

Multivariable Mendelian randomization (MVMR) uses genetic variants as instrumental variables to infer the direct effects of multiple exposures on an outcome. However, unlike univariable Mendelian randomization, MVMR often faces greater…

Methodology · Statistics 2025-08-19 Yinxiang Wu , Hyunseung Kang , Ting Ye

Mendelian randomization is a powerful tool for causal inference in observational studies. The two-sample summary-data design, which estimates genetic associations with exposures and outcomes in separate cohorts, is the most widely used…

Methodology · Statistics 2026-04-29 Dingke Tang , Xuming He , Shu Yang

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

Mediation analysis aims to separate the indirect effect through mediators from the direct effect of the exposure on the outcome. It is challenging to perform mediation analysis with neuroimaging data which involves high dimensionality,…

Methodology · Statistics 2025-12-30 Yuliang Xu , Timothy D Johnson , Mary Heitzeg , Jian Kang

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

Mediation analysis has traditionally focused on outcome-level summary contrasts, such as mean effects, which may obscure substantial distributional changes induced by complex and nonlinear causal mechanisms. We propose Distributional Causal…

Machine Learning · Statistics 2026-05-05 Jinlun Zhang , Haoneng Huang , Zishu Zhan , Chunquan Ou

Common psychiatric and brain disorders are highly heritable and affected by a number of genetic risk factors, yet the mechanism by which these genetic factors contribute to the disorders through alterations in brain structure and function…

Methodology · Statistics 2025-11-26 Neng Wang , Eric V. Slud , Tianzhou Ma

Background In a study performed on multiplex Multiple Sclerosis (MS) Sardinian families to identify disease causing plasma proteins, application of Mendelian Randomization (MR) methods encounters difficulties due to relatedness of…

This paper aims to provide practitioners of causal mediation analysis with a better understanding of estimation options. We take as inputs two familiar strategies (weighting and model-based prediction) and a simple way of combining them…

Genome-wide association studies(GWAS) have proven to be highly useful in revealing the genetic basis of complex diseases. At present, most GWAS are studies of a particular single disease diagnosis against controls. However, in practice, an…

Genomics · Quantitative Biology 2021-01-01 Liangying Yin , Carlos Kwan-long Chau , Yu-Ping Lin , Pak-Chung Sham , Hon-Cheong So

Analyses of causal mediation often involve exposure-induced confounders or, relatedly, multiple mediators. In such applications, researchers aim to estimate a variety of different quantities, including interventional direct and indirect…

Methodology · Statistics 2025-06-18 Jesse Zhou , Geoffrey T. Wodtke

Mendelian randomization is the use of genetic variants as instrumental variables to assess whether a risk factor is a cause of a disease outcome. Increasingly, Mendelian randomization investigations are conducted on the basis of summarized…

Applications · Statistics 2015-12-15 Stephen Burgess , Jack Bowden

\textbf{Background:} Mediation analysis is widely used to investigate how treatments and programs exert their effects, but standard ordinary least squares (OLS) inference can be unreliable when regression errors are non-Gaussian. In medical…

Methodology · Statistics 2026-04-10 Mijeong Kim

The method of multivariable Mendelian randomization uses genetic variants to instrument multiple exposures, to estimate the effect that a given exposure has on an outcome conditional on all other exposures included in a linear model.…

Methodology · Statistics 2024-08-20 Ashish Patel , James Lane , Stephen Burgess

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…

We expand Mendelian Randomization (MR) methodology to deal with randomly missing data on either the exposure or the outcome variable, and furthermore with data from nonindependent individuals (eg components of a family). Our method rests on…

Multivariate Mendelian randomization (MVMR) is a statistical technique that uses sets of genetic instruments to estimate the direct causal effects of multiple exposures on an outcome of interest. At genomic loci with pleiotropic gene…

Methodology · Statistics 2024-09-23 Mariyam Khan , Adriaan-Alexander Ludl , Sean Bankier , Johan Bjorkegren , Tom Michoel

The prevailing method of analyzing GWAS data is still to test each marker individually, although from a statistical point of view it is quite obvious that in case of complex traits such single marker tests are not ideal. Recently several…

Applications · Statistics 2015-06-19 Erich Dolejsi , Bernhard Bodenstorfer , Florian Frommlet