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Methods for the Analysis of Multiple Epigenomic Mediators in Environmental Epidemiology

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Abstract

Purpose of Review

Epigenetic changes can be highly influenced by environmental factors and have in turn been proposed to influence chronic disease. Being able to quantify to which extent epigenomic processes are mediators of the association between environmental exposures and diseases is of interest for epidemiologic research. In this review, we summarize the proposed mediation analysis methods with applications to epigenomic data.

Recent Findings

The ultra-high dimensionality and high correlations that characterize omics data have hindered the precise quantification of mediated effects. Several methods have been proposed to deal with mediation in high-dimensional settings, including methods that incorporate dimensionality reduction techniques to the mediation algorithm.

Summary

Although important methodological advances have been conducted in the previous years, key challenges such as the development of sensitivity analyses, dealing with mediator-mediator interactions, including environmental mixtures as exposures, or the integration of different omic data should be the focus of future methodological developments for epigenomic mediation analysis.

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Funding

Drs. Domingo-Relloso and Valeri received funding from the National Institute of Environmental Health Sciences (P42ES033719). Dr. Tellez-Plaza received funding from the Strategic Action for Research in Health sciences (CP12/03080 and PI15/00071), which are initiatives from Instituto de Salud Carlos III and the Spanish Ministry of Science and Innovation and co-funded with European Funds for Regional Development (FEDER) and by the State Agency for Research (PID2019-108973RB- C21). The opinions and views expressed in this article are those of the authors and do not necessarily represent the official position of the Instituto de Salud Carlos III (Spain).

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Authors and Affiliations

  1. Department of Biostatistics, Columbia University Mailman School of Public Health, 722 West 168Th Street, New York, NY, 10032, USA

    Arce Domingo-Relloso & Linda Valeri

  2. Department of Chronic Diseases Epidemiology, National Center for Epidemiology, Carlos III Health Institute, Madrid, Spain

    Maria Tellez-Plaza

  3. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA

    Linda Valeri

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  1. Arce Domingo-Relloso
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A.D. wrote the main manuscript text. All authors reviewed the manuscript.

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Correspondence to Arce Domingo-Relloso.

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Domingo-Relloso, A., Tellez-Plaza, M. & Valeri, L. Methods for the Analysis of Multiple Epigenomic Mediators in Environmental Epidemiology. Curr Envir Health Rpt 11, 109–117 (2024). https://doi.org/10.1007/s40572-024-00436-9

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