title: Prenatal exposure to maternal smoking and offspring DNA methylation across the lifecourse: findings from the Avon Longitudinal Study of Parents and Children (ALSPAC).
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.
authors.affiliation: MRC Integrative Epidemiology Unit (IEU), School of Social and Community Medicine, University of Bristol, Bristol BS8 2BN, UK and.
authors.forename: Rebecca C
authors.initials: RC
authors.lastname: Richmond
authors.affiliation: MRC Integrative Epidemiology Unit (IEU), School of Social and Community Medicine, University of Bristol, Bristol BS8 2BN, UK and.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Simpkin
authors.affiliation: MRC Integrative Epidemiology Unit (IEU), School of Social and Community Medicine, University of Bristol, Bristol BS8 2BN, UK and.
authors.forename: Geoff
authors.initials: G
authors.lastname: Woodward
authors.affiliation: MRC Integrative Epidemiology Unit (IEU), School of Social and Community Medicine, University of Bristol, Bristol BS8 2BN, UK and.
authors.forename: Tom R
authors.initials: TR
authors.lastname: Gaunt
authors.affiliation: MRC Integrative Epidemiology Unit (IEU), School of Social and Community Medicine, University of Bristol, Bristol BS8 2BN, UK and.
authors.forename: Oliver
authors.initials: O
authors.lastname: Lyttleton
authors.affiliation: MRC Integrative Epidemiology Unit (IEU), School of Social and Community Medicine, University of Bristol, Bristol BS8 2BN, UK and.
authors.forename: Wendy L
authors.initials: WL
authors.lastname: McArdle
authors.affiliation: MRC Integrative Epidemiology Unit (IEU), School of Social and Community Medicine, University of Bristol, Bristol BS8 2BN, UK and.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Ring
authors.affiliation: MRC Integrative Epidemiology Unit (IEU), School of Social and Community Medicine, University of Bristol, Bristol BS8 2BN, UK and.
authors.forename: Andrew D A C
authors.initials: AD
authors.lastname: Smith
authors.affiliation: MRC Integrative Epidemiology Unit (IEU), School of Social and Community Medicine, University of Bristol, Bristol BS8 2BN, UK and.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Timpson
authors.affiliation: MRC Integrative Epidemiology Unit (IEU), School of Social and Community Medicine, University of Bristol, Bristol BS8 2BN, UK and.
authors.forename: Kate
authors.initials: K
authors.lastname: Tilling
authors.affiliation: MRC Integrative Epidemiology Unit (IEU), School of Social and Community Medicine, University of Bristol, Bristol BS8 2BN, UK and.
authors.forename: George
authors.initials: G
authors.lastname: Davey Smith
authors.affiliation: MRC Integrative Epidemiology Unit (IEU), School of Social and Community Medicine, University of Bristol, Bristol BS8 2BN, UK and Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne NE1 3BZ, UK caroline.relton@bristol.ac.uk.
authors.forename: Caroline L
authors.initials: CL
authors.lastname: Relton
mesh_terms: D000293:Adolescent; D002648:Child; D015331:Cohort Studies; D019175:DNA Methylation; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008137:Longitudinal Studies; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D010375:Pedigree; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics* / Q000378:metabolism; D012907:Smoking / Q000009:adverse effects*