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Transl Psychiatry. 2019 Feb 15;9(1):92. doi: 10.1038/s41398-019-0430-9.

Establishing a generalized polyepigenetic biomarker for tobacco smoking.

Author information

1
Department of Psychology and Neuroscience, Duke University, Durham, NC, USA. Karen.sugden@duke.edu.
2
Center for Genomic and Computational Biology, Duke University, Durham, NC, USA. Karen.sugden@duke.edu.
3
University of Exeter Medical School, University of Exeter, Exeter, UK.
4
Social, Genetic, and Developmental Psychiatry Research Centre, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK.
5
Department of Epidemiology & Butler Aging Center, Columbia University Mailman School of Public Health, New York, NY, USA.
6
Department of Oral Sciences, University of Otago, Dunedin, New Zealand.
7
Center for Genomic and Computational Biology, Duke University, Durham, NC, USA.
8
Department of Preventive and Social Medicine, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
9
Department of Psychology and Neuroscience, Duke University, Durham, NC, USA.
10
Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC, USA.
11
Dunedin Multidisciplinary Health and Development Research Unit, University of Otago, Dunedin, New Zealand.

Abstract

Large-scale epigenome-wide association meta-analyses have identified multiple 'signatures'' of smoking. Drawing on these findings, we describe the construction of a polyepigenetic DNA methylation score that indexes smoking behavior and that can be utilized for multiple purposes in population health research. To validate the score, we use data from two birth cohort studies: The Dunedin Longitudinal Study, followed to age-38 years, and the Environmental Risk Study, followed to age-18 years. Longitudinal data show that changes in DNA methylation accumulate with increased exposure to tobacco smoking and attenuate with quitting. Data from twins discordant for smoking behavior show that smoking influences DNA methylation independently of genetic and environmental risk factors. Physiological data show that changes in DNA methylation track smoking-related changes in lung function and gum health over time. Moreover, DNA methylation changes predict corresponding changes in gene expression in pathways related to inflammation, immune response, and cellular trafficking. Finally, we present prospective data about the link between adverse childhood experiences (ACEs) and epigenetic modifications; these findings document the importance of controlling for smoking-related DNA methylation changes when studying biological embedding of stress in life-course research. We introduce the polyepigenetic DNA methylation score as a tool both for discovery and theory-guided research in epigenetic epidemiology.

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