Maternal Gestational Diabetes Mellitus and Newborn DNA Methylation: Findings From the Pregnancy and Childhood Epigenetics Consortium
Year: 2019
Type: article
Abstract: OBJECTIVE Maternal gestational diabetes mellitus (GDM) has been associated with adverse outcomes in the offspring. Growing evidence suggests that the epigenome may play a role, but most previous studies have been small and adjusted for few covariates. The current study meta-analyzed the association between maternal GDM and cord blood DNA methylation in the Pregnancy and Childhood Epigenetics (PACE) consortium. RESEARCH DESIGN AND METHODS Seven pregnancy cohorts (3,677 mother-newborn pairs [317 with GDM]) contributed results from epigenome-wide association studies, using DNA methylation data acquired by the Infinium HumanMethylation450 BeadChip array. Associations between GDM and DNA methylation were examined using robust linear regression, with adjustment for potential confounders. Fixed-effects meta-analyses were performed using METAL. Differentially methylated regions (DMRs) were identified by taking the intersection of results obtained using two regional approaches: comb-p and DMRcate. RESULTS Two DMRs were identified by both comb-p and DMRcate. Both regions were hypomethylated in newborns exposed to GDM in utero compared with control subjects. One DMR (chr 1: 248100345–248100614) was located in the OR2L13 promoter, and the other (chr 10: 135341870–135342620) was located in the gene body of CYP2E1. Individual CpG analyses did not reveal any differentially methylated loci based on a false discovery rate–adjusted P value threshold of 0.05. CONCLUSIONS Maternal GDM was associated with lower cord blood methylation levels within two regions, including the promoter of OR2L13, a gene associated with autism spectrum disorder, and the gene body of CYP2E1, which is upregulated in type 1 and type 2 diabetes. Future studies are needed to understand whether these associations are causal and possible health consequences.
Source: Diabetes Care
DOI: 10.2337/dc19-0524
Authors: Caitlin G. Howe, Bianca Cox, Ruby Fore, James Jungius, Tuomas Kvist, Samantha Lent, Harriet E. Miles, Lucas A. Salas, Sheryl Rifas-Shiman, Anne P. Starling, Paul Yousefi, Christine Ladd-Acosta, Andrea Baccarelli, Elisabeth B. Binder, Vaia Lida Chatzi, Darina Czamara, Dana Dabelea, Dawn L. DeMeo, Akram Ghantous, Zdenko Herceg, Eero Kajantie, Jari M.T. Lahti, Debbie A. Lawlor, Augusto Litonjua, Tim S. Nawrot, Ellen A. Nohr, Emily Oken, Costanza Pizzi, Michelle Plusquin, Katri Räikkönen, Caroline L. Relton, Gemma C. Sharp, Thorkild I.A. Sørensen, Jordi Sunyer, Martine Vrijheid, Weiming Zhang, Marie-France Hivert, Carrie V. Breton
Institutions: University of Southern California, Hasselt University, Harvard University, Harvard Pilgrim Health Care, University of Bristol, MRC Integrative Epidemiology Unit, University of Helsinki, Dartmouth College, Universitat Pompeu Fabra, Barcelona Institute for Global Health, Colorado School of Public Health, University of Colorado Anschutz, Johns Hopkins University, Columbia University, Emory University, Max Planck Institute of Psychiatry, University of Crete, Maastricht University, Brigham and Women's Hospital, Centre international de recherche sur le cancer, Norwegian University of Science and Technology, Oulu University Hospital, Helsinki University Hospital, Finnish Institute for Health and Welfare, Helsinki Children's Hospital, University of Oulu, NIHR Bristol Biomedical Research Centre, KU Leuven, University of Southern Denmark, University of Turin, University of Copenhagen, Novo Nordisk Foundation Center for Basic Metabolic Research, Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública, Massachusetts General Hospital
Language: English
Subfield: Obstetrics and Gynecology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: World Health Organization, University of Southern California, Centre International de Recherche sur le Cancer, Wellcome Trust, National Institute for Health and Care Research, Novo Nordisk Fonden, Medical Research Council, Biotechnology and Biological Sciences Research Council, National Heart, Lung, and Blood Institute, National Cancer Institute, National Institute of Nursing Research, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Environmental Health Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: Reproductive and cardio-metabolic health, Exploring the Fuel-Mediated Programming of Neonatal Growth, Environmental Genomics, The Avon Longitudinal Study of Parents and Children (ALSPAC): A multi-generation, longitudinal resource, The Avon Longitudinal Study of Parents and Children (ALSPAC): A multi- generation, longitudinal resource focusing on life course health and well- being., Maternal and Developmental Risks from Environmental and Social Stressors (MADRES), Accessible resource for integrated epigenomics studies (ARIES), G4738452938, 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, A mechanistic study of prenatal air pollution exposure and offspring obesity risk, NIHR Senior Investigator Award, Accessible resource for integrated epigenomics studies (ARIES), A mechanistic study of prenatal air pollution exposure and offspring obesity risk, Novel Epigenomic Biomarkers of Prenatal Risk Factors, and Childhood Obesity, Early Life DNA Methylation and Childhood Allergic Disease, G6839661530, Epigenetic Epidemiology, G7095874527, Prenatal Metal Mixtures, Fetal Growth, and the Role of MicroRNAs, Metabolomic and Epigenomic Mechanisms in Developmental Overnutrition., G7728844558, Endocrine disruptors, epigenetic programming and neonatal outcomes, Cancer Center Support Grant, Environmental Exposures, Host Factors and Human Disease, Colorado Nutrition Obesity Research Center, Prenatal environmental determinants of health in young adulthood: a lifecourse approach, Boston Area Nutrition Obesity Research Center (NORC)
OpenAlex ID: W2979921170