Maternal Smoking During Pregnancy Induces Persistent Epigenetic Changes Into Adolescence, Independent of Postnatal Smoke Exposure and Is Associated With Cardiometabolic Risk
Year: 2019
Type: article
Study design: Observational Study
Abstract: 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. Further, 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 Western Australian Pregnancy Cohort (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 DMCpGs identified were analysed 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 (males and females), diastolic blood pressure (females only) or HDL-C (males 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.
Source: Frontiers in Genetics
Institutions: The Kids Research Institute Australia, The University of Western Australia, Curtin University, University of Southampton, Royal Children's Hospital, Deakin University, Murdoch Children's Research Institute, University Hospital Southampton NHS Foundation Trust, NIHR Southampton Biomedical Research Centre, MRC Lifecourse Epidemiology Unit, Royal Perth Hospital, University of Tasmania, Menzies Institute for Medical Research, University of Newcastle Australia
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,950
Funders: University of Notre Dame, Wellcome Trust, Australian Government, National Institute for Health and Care Research, British Heart Foundation, European Commission, Raine Medical Research Foundation, Women and Infants Research Foundation, Curtin University of Technology, Edith Cowan University, Murdoch University, University of Notre Dame Australia, Government of Western Australia, National Institute for Health Research Southampton Biomedical Research Centre, Horizon 2020 Framework Programme, Seventh Framework Programme, Medical Research Council, National Health and Medical Research Council, Erasmus+
Awards: G1093531541, G1140988124, G1277089031, Early Life Programming of Cardiovascular Disease, G183778332, G1938092250, G2125390887, Food-based solutions for Optimal vitamin D Nutrition and health through the life cycle, G2473961061, THE CYCLE OF OBESITY: Two generations of a pregnancy cohort to investigate obesity epigenetics, The Avon Longitudinal Study of Parents and Children (ALSPAC): A multi-generation, longitudinal resource, G3207356259, G3381566145, NIHR Senior Investigator Award, Early-life stressors and LifeCycle health, LIFECYCLE - Early Life Stressors and LifeCycle Health, G3650892880, The Avon Longitudinal Study of Parents and Children (ALSPAC): A multi- generation, longitudinal resource focusing on life course health and well- being., G393177772, Research Fellowship, G462585257, NIHR Senior Investigator Award, The Avon Longitudinal Study of Parents and Children: An international resource for population
genomics and lifecourse epidemiology. Core Programme Support 2011-2015 and Core programme support 2014-2019, G4964355645, G5090859494, G5377879826, G5605571342, G5643282797, G5702163051, Epigenetic biomarkers and determinants of cardiovascular risk in children, G587834012, G7295670324, G7311105212, Nutrition, Development and Lifelong Health: Studies in European Populations, G8520667178, G878312145, Long-term effects of early nutrition on later health
OpenAlex ID: W2963973585