Mendelian Randomization and the Environmental Epigenetics of Health: a Systematic Review
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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.
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.
KeywordsSystematic 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.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
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