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Mendelian Randomization and the Environmental Epigenetics of Health: a Systematic Review

  • Environmental Epigenetics (A Baccarelli and A Cardenas, Section Editors)
  • Published:
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Abstract

Purpose of Review

Epigenetic modifications are environmentally responsive and may play a mechanistic role in the development of disease. Mendelian randomization uses genetic variation to assess the causal effect of modifiable exposures on health outcomes. We conducted a systematic review of Mendelian randomization studies evaluating the causal role of DNA methylation (DNAm) changes on the development of health states, emphasizing on studies that formally evaluate exposure-DNAm, in addition to DNAm-outcome, causal associations.

Recent Findings

We identified 15 articles, 4 of them including an environmental determinant of DNAm, including self-reported tobacco smoke exposure, in utero tobacco smoke exposure, measured vitamin B12, and glycemia.

Summary

Selected articles suggest a causal association of DNAm with some cardiometabolic endpoints. DNAm seemed to partly explain the association of postnatal and prenatal exposure to tobacco smoke and vitamin B12 with inflammation biomarkers, birth weight, and cognitive outcomes, respectively. However, the current evidence is not sufficient to infer causality. Additional Mendelian randomization studies from large epidemiologic samples are needed to support the causal role of environmental factors as determinants of health-related epigenetic modifications.

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Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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Acknowledgments

M.G.P. was supported by the AstraZeneca Foundation, Spain (“III Premio Jóvenes Investigadores, Programa de Fomento de los Jóvenes Científicos Españoles,” Principal Investigator: M.T.P.). The findings and conclusions in this article are those of the authors and do not necessarily reflect the views of the Carlos III Health Institutes, Madrid.

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Author notes

  1. Maria Grau-Perez and Golareh Agha contributed equally to this work.

Authors and Affiliations

  1. Area of Cardiometabolic and Renal Risk, Biomedical Research Institute Hospital Clinic of Valencia (INCLIVA), Av. Menendez Pelayo 4 accesorio, 46010, Valencia, Spain

    Maria Grau-Perez & Maria Tellez-Plaza

  2. Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, 722 W 168th St, New York, NY, 10032, USA

    Maria Grau-Perez & Golareh Agha

  3. Department of Statistics and Operational Research, University of Valencia, Av. Dr. Moliner 50, Valencia, Burjassot, 46100, Spain

    Maria Grau-Perez & Jose D. Bermudez

  4. Clinical Trial Service Unit & Epidemiological Studies (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK

    Yuanjie Pang

  5. Department of Chronic Diseases Epidemiology, National Center for Epidemiology, National Institutes for Health Carlos III, C/ Monforte de Lemos, 5. Pabellón 12, 28029, Madrid, Spain

    Maria Tellez-Plaza

  6. Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, 615 N Wolfe St, Baltimore, MD, 21205, USA

    Maria Tellez-Plaza

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Correspondence to Maria Grau-Perez.

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Maria Grau-Perez, Golareh Agha, Yuanjie Pang, José Bermudez, and Maria Tellez-Plaza declare that they have no conflict of interest.

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Grau-Perez, M., Agha, G., Pang, Y. et al. Mendelian Randomization and the Environmental Epigenetics of Health: a Systematic Review. Curr Envir Health Rpt 6, 38–51 (2019). https://doi.org/10.1007/s40572-019-0226-3

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