Cell Types in Environmental Epigenetic Studies: Biological and Epidemiological Frameworks
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EARLY LIFE ENVIRONMENTAL HEALTH (H VOLK AND J BUCKLEY, SECTION EDITORS)
Cell Types in Environmental Epigenetic Studies: Biological and Epidemiological Frameworks Kyle A. Campbell 1
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Justin A. Colacino 2
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Sung Kyun Park 1,2
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Kelly M. Bakulski 1
Published online: 13 August 2020 # Springer Nature Switzerland AG 2020
Abstract Purpose of Review This article introduces the roles of perinatal DNA methylation in human health and disease, highlights the challenges of tissue and cellular heterogeneity to studying DNA methylation, summarizes approaches to overcome these challenges, and offers recommendations in conducting research in environmental epigenetics. Recent Findings Epigenetic modifications are essential for human development and are labile to environmental influences, especially during gestation. Epigenetic dysregulation is also a hallmark of multiple diseases. Environmental epigenetic studies routinely measure DNA methylation in readily available tissues. However, tissues and cell types exhibit specific epigenetic patterning and heterogeneity between samples complicates epigenetic studies. Failure to account for cell-type heterogeneity limits identification of biological mechanisms and biases study results. Summary Tissue-level epigenetic measures represent a convolution of epigenetic signals from individual cell types. Tissuespecific epigenetics is an evolving field and the use of disease-affected target, surrogate, or multiple tissues has inherent trade-offs and affects inference. Likewise, experimental and bioinformatic approaches to accommodate cell-type heterogeneity have varying assumptions and inherent trade-offs that affect inference. The relationships between exposure, disease, tissue-level DNA methylation, cell type–specific DNA methylation, and cell-type heterogeneity must be carefully considered in study design and analysis. Causal diagrams can inform study design and analytic strategies. Properly addressing cell-type heterogeneity limits sources of potential bias, avoids misinterpretation of study results, and allows investigators to distinguish shifts in cell-type proportions from direct changes to cellular epigenetic programming, both of which provide insights into environmental disease etiology and aid development of novel methods for prevention and treatment. Keywords Epigenetics . Environment . DNA methylation . Cellular heterogeneity . Epidemiology . Tissue
Introduction to Epigenetics Epigenetics refers to the programming of cellular state, memory, or fate not attributable to changes in DNA sequence [1, 2]. Epigenetic modifications include DNA methylation, histone modifications, and non-coding RNAs [3]. DNA This article is part of the Topical Collection on Early Life Environmental Health * Kyle A. Campbell [email protected] 1
Department of Epidemiology, University of Michigan School of Public Health, University of Michigan, Ann Arbor, MI, USA
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Department of Environmental Health Sciences, University of Michigan School of Public Health, University of Michigan, Ann Arbor, MI, USA
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