Epigenome-wide meta-analysis of blood DNA methylation in newborns and children identifies numerous loci related to gestational age
Year: 2020
Type: review
Abstract: BACKGROUND: Preterm birth and shorter duration of pregnancy are associated with increased morbidity in neonatal and later life. As the epigenome is known to have an important role during fetal development, we investigated associations between gestational age and blood DNA methylation in children. METHODS: We performed meta-analysis of Illumina's HumanMethylation450-array associations between gestational age and cord blood DNA methylation in 3648 newborns from 17 cohorts without common pregnancy complications, induced delivery or caesarean section. We also explored associations of gestational age with DNA methylation measured at 4-18 years in additional pediatric cohorts. Follow-up analyses of DNA methylation and gene expression correlations were performed in cord blood. DNA methylation profiles were also explored in tissues relevant for gestational age health effects: fetal brain and lung. RESULTS: , of which 3343 were novel. These were annotated to 4966 genes. After restricting findings to at least three significant adjacent CpGs, we identified 1276 CpGs annotated to 325 genes. Results were generally consistent when analyses were restricted to term births. Cord blood findings tended not to persist into childhood and adolescence. Pathway analyses identified enrichment for biological processes critical to embryonic development. Follow-up of identified genes showed correlations between gestational age and DNA methylation levels in fetal brain and lung tissue, as well as correlation with expression levels. CONCLUSIONS: We identified numerous CpGs differentially methylated in relation to gestational age at birth that appear to reflect fetal developmental processes across tissues. These findings may contribute to understanding mechanisms linking gestational age to health effects.
Source: Genome Medicine
Authors: Simon Kebede Merid, Alexei Novoloaca, Gemma C. Sharp, Leanne K. Küpers, Alvin T. Kho, Ritu Roy, Lu Gao, Isabella Annesi-Maesano, Pooja Jain, Michelle Plusquin, Manolis Kogevinas, Catherine Allard, Florianne O. Vehmeijer, Nabila Kazmi, Lucas A. Salas, Faisal I. Rezwan, Hongmei Zhang, Sylvain Sebert, Darina Czamara, Sheryl L. Rifas-Shiman, Phillip E. Melton, Debbie A. Lawlor, Göran Pershagen, Carrie V. Breton, Karen Huen, Nour Baiz, Luigi Gagliardi, Tim S. Nawrot, Eva Corpeleijn, Patrice Perron, Liesbeth Duijts, Ellen Aagaard Nohr, Mariona Bustamante, Susan L. Ewart, Wilfried Karmaus, Shanshan Zhao, Christian M. Page, Zdenko Herceg, Marjo-Riitta Jarvelin, Jari Lahti, Andrea A. Baccarelli, Denise Anderson, Priyadarshini Kachroo, Caroline L. Relton, Anna Bergström, Brenda Eskenazi, Munawar Hussain Soomro, Paolo Vineis, Harold Snieder, Luigi Bouchard, Vincent W. Jaddoe, Thorkild I. A. Sørensen, Martine Vrijheid, S. Hasan Arshad, John W. Holloway, Siri E. Håberg, Per Magnus, Terence Dwyer, Elisabeth B. Binder, Dawn L. DeMeo, Judith M. Vonk, John Newnham, Kelan G. Tantisira, Inger Kull, Joseph L. Wiemels, Barbara Heude, Jordi Sunyer, Wenche Nystad, Monica C. Munthe-Kaas, Katri Räikkönen, Emily Oken, Rae-Chi Huang, Scott T. Weiss, Josep Maria Antó, Jean Bousquet, Ashish Kumar, Cilla Söderhäll, Catarina Almqvist, Andres Cardenas, Olena Gruzieva, Cheng-Jian Xu, Sarah E. Reese, Juha Kere, Petter Brodin, Olivia Solomon, Matthias Wielscher, Nina Holland, Akram Ghantous, Marie-France Hivert, Janine F. Felix, Gerard H. Koppelman, Stephanie J. London, Erik Melén
Institutions: Karolinska Institutet, Stockholm South General Hospital, Centre international de recherche sur le cancer, University of Bristol, MRC Integrative Epidemiology Unit, University Medical Center Groningen, University of Groningen, Wageningen University & Research, Boston Children's Hospital, Harvard University, University of California, San Francisco, UCSF Helen Diller Family Comprehensive Cancer Center, University of Southern California, Southern California University of Health Sciences, Inserm, Sorbonne Université, Institut Pierre Louis d‘Épidémiologie et de Santé Publique, Imperial College London, Hasselt University, Universitat Pompeu Fabra, Municipal Institute for Medical Research, Barcelona Institute for Global Health, Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública, Hospital del Mar Research Institute, Université de Sherbrooke, Centre Hospitalier Universitaire de Sherbrooke, Erasmus MC, Dartmouth College, Cranfield University, University of Memphis, University of Oulu, Max Planck Institute of Psychiatry, Harvard Pilgrim Health Care, The University of Western Australia, Curtin University, NIHR Bristol Biomedical Research Centre, Region Stockholm, University of California, Berkeley, Ospedale Versilia, Azienda USL Toscana Nord Ovest, Universitair Ziekenhuis Leuven, National Institute for Health and Care Research, KU Leuven, University of Southern Denmark, Michigan State University, National Institutes of Health, National Institute of Environmental Health Sciences, Norwegian Institute of Public Health, Oulu University Hospital, MRC Centre for Environment and Health, University of Helsinki, University of Turku, Columbia University Irving Medical Center, Columbia University, The Kids Research Institute Australia, Brigham and Women's Hospital, Centre Intégré Universitaire de Santé et de Services Sociaux du Saguenay–Lac-Saint-Jean, University of Copenhagen, Novo Nordisk Foundation Center for Basic Metabolic Research, David Hide Asthma and Allergy Research Centre, University of Southampton, University Hospital Southampton NHS Foundation Trust, The University of Melbourne, University of Oxford, Murdoch Children's Research Institute, Emory University, Sachs' Children and Youth Hospital, Sorbonne Paris Cité, Centre de Recherche Épidémiologie et Statistique, Université Paris Descartes, Oslo University Hospital, Centre Hospitalier Universitaire de Montpellier, Stiftung Charité, Charité - Universitätsmedizin Berlin, Swiss Tropical and Public Health Institute, University of Basel, Karolinska University Hospital, Folkhälsans Forskningscentrum, Science for Life Laboratory, Massachusetts General Hospital
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,290
Awards: G108165290, G1502031688, G216832024, The Avon Longitudinal Study of Parents and Children (ALSPAC): A multi- generation, longitudinal resource focusing on life course health and well- being., G4086346382, Accessible resource for integrated epigenomics studies (ARIES), MICRORNAS IN CIRCULATION: ONTOLOGIES OF ASTHMA SEVERITY AND TREATMENT (MICROCOAST), G5192599444, G5204329449, G6455880001, G6689231961, G7194418384, G801210579, A TRranslational approach to Identify Biomarkers for Asthma and Lung function impairment, G8782766175
OpenAlex ID: W3009067006