ArticleBriefings in bioinformatics2021
Gene-based mediation analysis in epigenetic studies.
Article in Briefings in bioinformatics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed.
- Gene set mediation analysis in high-dimensional epigenetic studies.Briefings in bioinformatics · 2026Article
- Integrative Analysis of Multimodal Omics Data.Annual review of statistics and its application · 2026Article
- MELODY: Mediation Analysis in Logistic Regression for High-Dimensional Mediators and a Binary Outcome.Genetic epidemiology · 2026Article
- CoxMDS: multiple data splitting for high-dimensional mediation analysis with survival outcomes in epigenome-wide studies.Briefings in bioinformatics · 2026Article
- Speeding up interval estimation for R2-based mediation effect of high-dimensional mediators via cross-fitting.Biostatistics (Oxford, England) · 2025Article
- MELODY: Mediation Analysis in Logistic Regression for High-Dimensional Mediators and a Binary Outcome.bioRxiv : the preprint server for biology · 2025Article
- Overexpression of OTX2 in human neural cells links depression risk genes.Translational psychiatry · 2025Article
- Causal Relationships Between Pregnancy, Menstrual History, and Endometrial Cancer With Mediating Effects of Metabolism-Related Traits.Human mutation · 2025Article
- Mediation analysis in longitudinal study with high-dimensional methylation mediators.Briefings in bioinformatics · 2024Article
- Speeding up interval estimation forbioRxiv : the preprint server for biology · 2024Article
- Methods for the Analysis of Multiple Epigenomic Mediators in Environmental Epidemiology.Current environmental health reports · 2024Review
- High-dimensional quantile mediation analysis with application to a birth cohort study of mother-newborn pairs.Bioinformatics (Oxford, England) · 2024Article
- Mediation effects of DNA methylation and hydroxymethylation on birth outcomes after prenatal per- and polyfluoroalkyl substances (PFAS) exposure in the Michigan mother-infant Pairs cohort.Clinical epigenetics · 2023Article
- DNA methylation as a potential mediator of the association between indoor air pollution and neurodevelopmental delay in a South African birth cohort.Clinical epigenetics · 2023Article
- A Bayesian model for identifying cancer subtypes from paired methylation profiles.Briefings in bioinformatics · 2023Article
- How can childhood maltreatment affect post-traumatic stress disorder in adult: Results from a composite null hypothesis perspective of mediation analysis.Frontiers in psychiatry · 2023Article
- DNA methylation and aeroallergen sensitization: The chicken or the egg?Clinical epigenetics · 2022Article
- HIMA2: high-dimensional mediation analysis and its application in epigenome-wide DNA methylation data.BMC bioinformatics · 2022Article
- Mediation analysis for survival data with high-dimensional mediators.Bioinformatics (Oxford, England) · 2021Article
- Childhood adversity correlates with stable changes in DNA methylation trajectories in children and converges with epigenetic signatures of prenatal stress.Neurobiology of stress · 2021Article
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Authors and funding
6 authors.
Funding
Abstract
Mediation analysis has been a useful tool for investigating the effect of mediators that lie in the path from the independent variable to the outcome. With the increasing dimensionality of mediators such as in (epi)genomics studies, high-dimensional mediation model is needed. In this work, we focus on epigenetic studies with the goal to identify important DNA methylations that act as mediators between an exposure disease outcome. Specifically, we focus on gene-based high-dimensional mediation analysis implemented with kernel principal component analysis to capture potential nonlinear mediation effect. We first review the current high-dimensional mediation models and then propose two gene-based analytical approaches: gene-based high-dimensional mediation analysis based on linearity assumption between mediators and outcome (gHMA-L) and gene-based high-dimensional mediation analysis based on nonlinearity assumption (gHMA-NL). Since the underlying true mediation relationship is unknown in practice, we further propose an omnibus test of gene-based high-dimensional mediation analysis (gHMA-O) by combing gHMA-L and gHMA-NL. Extensive simulation studies show that gHMA-L performs better under the model linear assumption and gHMA-NL does better under the model nonlinear assumption, while gHMA-O is a more powerful and robust method by combining the two. We apply the proposed methods to two datasets to investigate genes whose methylation levels act as important mediators in the relationship: (1) between alcohol consumption and epithelial ovarian cancer risk using data from the Mayo Clinic Ovarian Cancer Case-Control Study and (2) between childhood maltreatment and comorbid post-traumatic stress disorder and depression in adulthood using data from the Gray Trauma Project.
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