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Prenatal exposure to maternal smoking and offspring DNA methylation across the lifecourse: findings from the Avon Longitudinal Study of Parents and Children (ALSPAC)

Lookup NU author(s): Professor Caroline Relton

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).

Abstract

Maternal smoking during pregnancy has been found to influence newborn DNA methylation in genes involved in fundamental developmental processes. It is pertinent to understand the degree to which the offspring methylome is sensitive to the intensity and duration of prenatal smoking. An investigation of the persistence of offspring methylation associated with maternal smoking and the relative roles of the intrauterine and postnatal environment is also warranted. In the Avon Longitudinal Study of Parents and Children, we investigated associations between prenatal exposure to maternal smoking and offspring DNA methylation at multiple time points in approximately 800 mother-offspring pairs. In cord blood, methylation at 15 CpG sites in seven gene regions (AHRR, MYO1G, GFI1, CYP1A1, CNTNAP2, KLF13 and ATP9A) was associated with maternal smoking, and a dose-dependent response was observed in relation to smoking duration and intensity. Longitudinal analysis of blood DNA methylation in serial samples at birth, age 7 and 17 years demonstrated that some CpG sites showed reversibility of methylation (GFI1, KLF13 and ATP9A), whereas others showed persistently perturbed patterns (AHRR, MYO1G, CYP1A1 and CNTNAP2). Of those showing persistence, we explored the effect of postnatal smoke exposure and found that the major contribution to altered methylation was attributed to a critical window of in utero exposure. A comparison of paternal and maternal smoking and offspring methylation showed consistently stronger maternal associations, providing further evidence for causal intrauterine mechanisms. These findings emphasize the sensitivity of the methylome to maternal smoking during early development and the long-term impact of such exposure.

Publication metadata

Author(s): Richmond RC, Simpkin AJ, Woodward G, Gaunt TR, Lyttleton O, McArdle WL, Ring SM, Smith ADAC, Timpson NJ, Tilling K, Smith GD, Relton CL

Publication type: Article

Publication status: Published

Journal: Human Molecular Genetics

Year: 2015

Volume: 24

Issue: 8

Pages: 2201-2217

Print publication date: 15/04/2015

Online publication date: 30/12/2014

Acceptance date: 22/12/2014

Date deposited: 12/04/2016

ISSN (print): 0964-6906

ISSN (electronic): 1460-2083

Publisher: Oxford University Press

URL: http://dx.doi.org/10.1093/hmg/ddu739

DOI: 10.1093/hmg/ddu739

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