Current Environmental Health Reports

, Volume 6, Issue 1, pp 38–51 | Cite as

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

  • Maria Grau-PerezEmail author
  • Golareh Agha
  • Yuanjie Pang
  • Jose D. Bermudez
  • Maria Tellez-Plaza
Environmental Epigenetics (A Baccarelli and A Cardenas, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Environmental Epigenetics


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.


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.


Systematic review Mendelian randomization DNA methylation Environmental Health outcomes 



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.

Compliance with Ethical Standards

Conflict of Interest

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

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Supplementary material

40572_2019_226_MOESM1_ESM.docx (60 kb)
ESM 1 (DOCX 60 kb)


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

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Maria Grau-Perez
    • 1
    • 2
    • 3
    Email author
  • Golareh Agha
    • 2
  • Yuanjie Pang
    • 4
  • Jose D. Bermudez
    • 3
  • Maria Tellez-Plaza
    • 1
    • 5
    • 6
  1. 1.Area of Cardiometabolic and Renal RiskBiomedical Research Institute Hospital Clinic of Valencia (INCLIVA)ValenciaSpain
  2. 2.Department of Environmental Health SciencesColumbia University Mailman School of Public HealthNew YorkUSA
  3. 3.Department of Statistics and Operational ResearchUniversity of ValenciaValenciaSpain
  4. 4.Clinical Trial Service Unit & Epidemiological Studies (CTSU), Nuffield Department of Population HealthUniversity of OxfordOxfordUK
  5. 5.Department of Chronic Diseases Epidemiology, National Center for EpidemiologyNational Institutes for Health Carlos IIIMadridSpain
  6. 6.Department of Environmental Health and EngineeringJohns Hopkins Bloomberg School of Public HealthBaltimoreUSA

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