Establishing a generalized polyepigenetic biomarker for tobacco smoking.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Sugden, K; Hannon, EJ; Arseneault, L; Belsky, DW; Broadbent, JM; Corcoran, DL; Hancox, RJ; Houts, RM; Moffitt, TE; Poulton, R; Prinz, JA; Thomson, WM; Williams, BS; Wong, CCY; Mill, J; Caspi, A

Published Date

  • February 15, 2019

Published In

Volume / Issue

  • 9 / 1

Start / End Page

  • 92 -

PubMed ID

  • 30770782

Pubmed Central ID

  • 30770782

Electronic International Standard Serial Number (EISSN)

  • 2158-3188

International Standard Serial Number (ISSN)

  • 2158-3188

Digital Object Identifier (DOI)

  • 10.1038/s41398-019-0430-9

Language

  • eng