Maternal Smoking During Pregnancy Induces Persistent Epigenetic Changes Into Adolescence, Independent of Postnatal Smoke Exposure and Is Associated With Cardiometabolic Risk

Background: Several studies have shown effects of current and maternal smoking during pregnancy on DNA methylation of CpG sites in newborns and later in life. Here, we hypothesized that there are long-term and persistent epigenetic effects following maternal smoking during pregnancy on adolescent of...

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Main Authors: Sebastian Rauschert, Phillip E. Melton, Graham Burdge, Jeffrey M. Craig, Keith M. Godfrey, Joanna D. Holbrook, Karen Lillycrop, Trevor A. Mori, Lawrence J. Beilin, Wendy H. Oddy, Craig Pennell, Rae-Chi Huang
Format: Article
Language:English
Published: Frontiers Media S.A. 2019-09-01
Series:Frontiers in Genetics
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Online Access:https://www.frontiersin.org/article/10.3389/fgene.2019.00770/full
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author Sebastian Rauschert
Phillip E. Melton
Phillip E. Melton
Graham Burdge
Jeffrey M. Craig
Jeffrey M. Craig
Keith M. Godfrey
Keith M. Godfrey
Joanna D. Holbrook
Karen Lillycrop
Trevor A. Mori
Lawrence J. Beilin
Wendy H. Oddy
Craig Pennell
Rae-Chi Huang
author_facet Sebastian Rauschert
Phillip E. Melton
Phillip E. Melton
Graham Burdge
Jeffrey M. Craig
Jeffrey M. Craig
Keith M. Godfrey
Keith M. Godfrey
Joanna D. Holbrook
Karen Lillycrop
Trevor A. Mori
Lawrence J. Beilin
Wendy H. Oddy
Craig Pennell
Rae-Chi Huang
author_sort Sebastian Rauschert
collection DOAJ
description Background: Several studies have shown effects of current and maternal smoking during pregnancy on DNA methylation of CpG sites in newborns and later in life. Here, we hypothesized that there are long-term and persistent epigenetic effects following maternal smoking during pregnancy on adolescent offspring DNA methylation, independent of paternal and postnatal smoke exposure. Furthermore, we explored the association between DNA methylation and cardiometabolic risk factors at 17 years of age.Materials and Methods: DNA methylation was measured using the Illumina HumanMethylation450K BeadChip in whole blood from 995 participants attending the 17-year follow-up of the Raine Study. Linear mixed effects models were used to identify differential methylated CpGs, adjusting for parental smoking during pregnancy, and paternal, passive, and adolescent smoke exposure. Additional models examined the association between DNA methylation and paternal, adolescent, and passive smoking over the life course. Offspring CpGs identified were analyzed against cardiometabolic risk factors (blood pressure, triacylglycerols (TG), high-density lipoproteins cholesterol (HDL-C), and body mass index).Results: We identified 23 CpGs (genome-wide p level: 1.06 × 10−7) that were associated 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 sensitivity analysis showed a dose-dependent relationship between maternal smoking and offspring methylation. These results changed little following adjustment for paternal, passive, or offspring smoking, and there were no CpGs identified that associated with these variables. Two of the 23 identified CpGs [cg00253568 (FTO) and cg00213123 (CYP1A1)] were associated with either TG (male and female), diastolic blood pressure (female only), or HDL-C (male only), after Bonferroni correction.Discussion: This study demonstrates a critical timing of cigarette smoke exposure over the life course for establishing persistent changes in DNA methylation into adolescence in a dose-dependent manner. There were significant associations between offspring CpG methylation and adolescent cardiovascular risk factors, namely, TG, HDL-C, and diastolic blood pressure. Future studies on current smoking habits and DNA methylation should consider the importance of maternal smoking during pregnancy and explore how the persistent DNA methylation effects of in utero smoke exposure increase cardiometabolic risk.
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spelling doaj.art-b4df1cf0169b44bf83ca1da37370c51a2022-12-21T18:44:33ZengFrontiers Media S.A.Frontiers in Genetics1664-80212019-09-011010.3389/fgene.2019.00770468076Maternal Smoking During Pregnancy Induces Persistent Epigenetic Changes Into Adolescence, Independent of Postnatal Smoke Exposure and Is Associated With Cardiometabolic RiskSebastian Rauschert0Phillip E. Melton1Phillip E. Melton2Graham Burdge3Jeffrey M. Craig4Jeffrey M. Craig5Keith M. Godfrey6Keith M. Godfrey7Joanna D. Holbrook8Karen Lillycrop9Trevor A. Mori10Lawrence J. Beilin11Wendy H. Oddy12Craig Pennell13Rae-Chi Huang14Telethon Kids Institute, University of Western Australia, Perth, WA, AustraliaCentre for Genetic Origins of Health and Disease, The University of Western Australia and Curtin University, Perth, WA, AustraliaSchool of Pharmacy and Biomedical Sciences, Curtin University, Bentley, WA, AustraliaHuman Development and Health, Faculty of Medicine, University of Southampton, Southampton, United KingdomEarly Life Epigenetics Group, MCRI, Royal Children’s Hospital, Flemington Road, Parkville, VIC, AustraliaCentre for Molecular and Medical Research, School of Medicine, Deakin University, Geelong, VIC, AustraliaHuman Development and Health, Faculty of Medicine, University of Southampton, Southampton, United KingdomMRC Lifecourse Epidemiology Unit and NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, United KingdomHuman Development and Health, Faculty of Medicine, University of Southampton, Southampton, United KingdomCentre for Biological Sciences, Faculty of Natural and Environmental Sciences, University of Southampton, Southampton, United KingdomMedical School, Royal Perth Hospital Unit, University of Western Australia, Perth, WA, AustraliaMedical School, Royal Perth Hospital Unit, University of Western Australia, Perth, WA, Australia0Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia1University of Newcastle, Newcastle, NSW, AustraliaTelethon Kids Institute, University of Western Australia, Perth, WA, AustraliaBackground: Several studies have shown effects of current and maternal smoking during pregnancy on DNA methylation of CpG sites in newborns and later in life. Here, we hypothesized that there are long-term and persistent epigenetic effects following maternal smoking during pregnancy on adolescent offspring DNA methylation, independent of paternal and postnatal smoke exposure. Furthermore, we explored the association between DNA methylation and cardiometabolic risk factors at 17 years of age.Materials and Methods: DNA methylation was measured using the Illumina HumanMethylation450K BeadChip in whole blood from 995 participants attending the 17-year follow-up of the Raine Study. Linear mixed effects models were used to identify differential methylated CpGs, adjusting for parental smoking during pregnancy, and paternal, passive, and adolescent smoke exposure. Additional models examined the association between DNA methylation and paternal, adolescent, and passive smoking over the life course. Offspring CpGs identified were analyzed against cardiometabolic risk factors (blood pressure, triacylglycerols (TG), high-density lipoproteins cholesterol (HDL-C), and body mass index).Results: We identified 23 CpGs (genome-wide p level: 1.06 × 10−7) that were associated 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 sensitivity analysis showed a dose-dependent relationship between maternal smoking and offspring methylation. These results changed little following adjustment for paternal, passive, or offspring smoking, and there were no CpGs identified that associated with these variables. Two of the 23 identified CpGs [cg00253568 (FTO) and cg00213123 (CYP1A1)] were associated with either TG (male and female), diastolic blood pressure (female only), or HDL-C (male only), after Bonferroni correction.Discussion: This study demonstrates a critical timing of cigarette smoke exposure over the life course for establishing persistent changes in DNA methylation into adolescence in a dose-dependent manner. There were significant associations between offspring CpG methylation and adolescent cardiovascular risk factors, namely, TG, HDL-C, and diastolic blood pressure. Future studies on current smoking habits and DNA methylation should consider the importance of maternal smoking during pregnancy and explore how the persistent DNA methylation effects of in utero smoke exposure increase cardiometabolic risk.https://www.frontiersin.org/article/10.3389/fgene.2019.00770/fullDNA methylationmaternal smoking during pregnancyepigeneticsRaine Studycardiometabolic healthadolescence
spellingShingle Sebastian Rauschert
Phillip E. Melton
Phillip E. Melton
Graham Burdge
Jeffrey M. Craig
Jeffrey M. Craig
Keith M. Godfrey
Keith M. Godfrey
Joanna D. Holbrook
Karen Lillycrop
Trevor A. Mori
Lawrence J. Beilin
Wendy H. Oddy
Craig Pennell
Rae-Chi Huang
Maternal Smoking During Pregnancy Induces Persistent Epigenetic Changes Into Adolescence, Independent of Postnatal Smoke Exposure and Is Associated With Cardiometabolic Risk
Frontiers in Genetics
DNA methylation
maternal smoking during pregnancy
epigenetics
Raine Study
cardiometabolic health
adolescence
title Maternal Smoking During Pregnancy Induces Persistent Epigenetic Changes Into Adolescence, Independent of Postnatal Smoke Exposure and Is Associated With Cardiometabolic Risk
title_full Maternal Smoking During Pregnancy Induces Persistent Epigenetic Changes Into Adolescence, Independent of Postnatal Smoke Exposure and Is Associated With Cardiometabolic Risk
title_fullStr Maternal Smoking During Pregnancy Induces Persistent Epigenetic Changes Into Adolescence, Independent of Postnatal Smoke Exposure and Is Associated With Cardiometabolic Risk
title_full_unstemmed Maternal Smoking During Pregnancy Induces Persistent Epigenetic Changes Into Adolescence, Independent of Postnatal Smoke Exposure and Is Associated With Cardiometabolic Risk
title_short Maternal Smoking During Pregnancy Induces Persistent Epigenetic Changes Into Adolescence, Independent of Postnatal Smoke Exposure and Is Associated With Cardiometabolic Risk
title_sort maternal smoking during pregnancy induces persistent epigenetic changes into adolescence independent of postnatal smoke exposure and is associated with cardiometabolic risk
topic DNA methylation
maternal smoking during pregnancy
epigenetics
Raine Study
cardiometabolic health
adolescence
url https://www.frontiersin.org/article/10.3389/fgene.2019.00770/full
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