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Abstract

Background: Several studies have shown effects of current and maternal smokingduring pregnancy on DNA methylation of CpG sites in newborns and later in life. Here, wehypothesized that there are long-term and persistent epigenetic effects following maternalsmoking during pregnancy on adolescent offspring DNA methylation, independentof paternal and postnatal smoke exposure. Furthermore, we explored the associationbetween DNA methylation and cardiometabolic risk factors at 17 years of age.Materials and Methods: DNA methylation was measured using the IlluminaHumanMethylation450K BeadChip in whole blood from 995 participants attendingthe 17-year follow-up of the Raine Study. Linear mixed effects models were used toidentify differential methylated CpGs, adjusting for parental smoking during pregnancy,and paternal, passive, and adolescent smoke exposure. Additional models examined theassociation between DNA methylation and paternal, adolescent, and passive smokingover the life course. Offspring CpGs identified were analyzed against cardiometabolic riskfactors (blood pressure, triacylglycerols (TG), high-density lipoproteins cholesterol (HDLC),and body mass index).Results: We identified 23 CpGs (genome-wide p level: 1.06 × 10−7) that wereassociated with maternal smoking during pregnancy, including associated genes AHRR(cancer development), FTO (obesity), CNTNAP2 (developmental processes), CYP1A1 (detoxification), MYO1G (cell signalling), and FRMD4A (nicotine dependence). A sensitivityanalysis showed a dose-dependent relationship between maternal smoking and offspringmethylation. These results changed little following adjustment for paternal, passive, oroffspring smoking, and there were no CpGs identified that associated with these variables.Two of the 23 identified CpGs [cg00253568 (FTO) and cg00213123 (CYP1A1)] wereassociated with either TG (male and female), diastolic blood pressure (female only), orHDL-C (male only), after Bonferroni correction.Discussion: This study demonstrates a critical timing of cigarette smoke exposure overthe life course for establishing persistent changes in DNA methylation into adolescencein a dose-dependent manner. There were significant associations between offspringCpG methylation and adolescent cardiovascular risk factors, namely, TG, HDL-C, anddiastolic blood pressure. Future studies on current smoking habits and DNA methylationshould consider the importance of maternal smoking during pregnancy and explorehow the persistent DNA methylation effects of in utero smoke exposure increasecardiometabolic risk.

Item Type:	Article
Authors/Creators:	Rauschert, S and Melton, PE and Burdge, G and Craig, JM and Godfrey, KM and Holbrook, JD and Lillycrop, K and Mori, TA and Beilin, LJ and Oddy, WH and Pennell, C and Huang, R-C
Keywords:	DNA methylation, maternal smoking during pregnancy, epigenetics, Raine Study, cardiometabolic health, adolescence
Journal or Publication Title:	Frontiers in Genetics
Publisher:	Frontiers Research Foundation
ISSN:	1664-8021
DOI / ID Number:	https://doi.org/10.3389/fgene.2019.00770
Copyright Information:	Copyright 2019 Rauschert, Melton, Burdge, Craig, Godfrey, Holbrook, Lillycrop, Mori, Beilin, Oddy, Pennell and Huang. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/
Related URLs:	Google Scholar: Oddy, WH
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