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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)

Smith, George Davey; Smith, Andrew D.A.C.; Richmond, Rebecca C.; Simpkin, Andrew J.; Woodward, Geoff; Gaunt, Tom R.; Lyttleton, Oliver; McArdle, Wendy L.; Ring, Susan M.; Smith, Andrew D. A. C.; Timpson, Nicholas J.; Tilling, Kate; Davey Smith, G; Relton, Caroline L.


George Davey Smith

Andrew D.A.C. Smith

Rebecca C. Richmond

Andrew J. Simpkin

Geoff Woodward

Tom R. Gaunt

Oliver Lyttleton

Wendy L. McArdle

Susan M. Ring

Nicholas J. Timpson

Kate Tilling

G Davey Smith

Caroline L. Relton


© The Author 2014. 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 methylomeis 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 alsowarranted. 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.


Smith, G. D., Smith, A. D., Richmond, R. C., Simpkin, A. J., Woodward, G., Gaunt, T. R., …Relton, C. L. (2015). Prenatal exposure to maternal smoking and offspring DNA methylation across the lifecourse: Findings from the Avon Longitudinal Study of Parents and Children (ALSPAC). Human Molecular Genetics, 24(8), 2201-2217.

Journal Article Type Article
Acceptance Date Dec 22, 2014
Online Publication Date Dec 30, 2014
Publication Date Jan 1, 2015
Journal Human Molecular Genetics
Print ISSN 0964-6906
Electronic ISSN 1460-2083
Publisher Oxford University Press (OUP)
Peer Reviewed Peer Reviewed
Volume 24
Issue 8
Pages 2201-2217
Keywords pregnancy; smoking; child; dna methylation; genes; methylation; mothers; parent; smoke; umbilical cord blood; smoking in pregnancy; prenatal exposure; intrauterine route of drug administration; alspac study; offspring
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