Meta-analysis of epigenome-wide association studies in newborns and children show widespread sex differences in blood DNA methylation
Year: 2022
Type: review
Abstract: Among children, sex-specific differences in disease prevalence, age of onset, and susceptibility have been observed in health conditions including asthma, immune response, metabolic health, some pediatric and adult cancers, and psychiatric disorders. Epigenetic modifications such as DNA methylation may play a role in the sexual differences observed in diseases and other physiological traits. We performed a meta-analysis of the association of sex and cord blood DNA methylation at over 450,000 CpG sites in 8438 newborns from 17 cohorts participating in the Pregnancy And Childhood Epigenetics (PACE) Consortium. We also examined associations of child sex with DNA methylation in older children ages 5.5–10 years from 8 cohorts (n = 4268). In newborn blood, sex was associated at Bonferroni level significance with differences in DNA methylation at 46,979 autosomal CpG sites (p < 1.3 × 10−7) after adjusting for white blood cell proportions and batch. Most of those sites had lower methylation levels in males than in females. Of the differentially methylated CpG sites identified in newborn blood, 68% (31,727) met look-up level significance (p < 1.1 × 10−6) in older children and had methylation differences in the same direction. This is a large-scale meta-analysis examining sex differences in DNA methylation in newborns and older children. Expanding upon previous studies, we replicated previous findings and identified additional autosomal sites with sex-specific differences in DNA methylation. Differentially methylated sites were enriched in genes involved in cancer, psychiatric disorders, and cardiovascular phenotypes.
Authors: Olivia Solomon, Karen Huen, Paul Yousefi, Leanne K. Küpers, Juan R. González, Matthew Suderman, Sarah E. Reese, Christian M. Page, Olena Gruzieva, Peter Rzehak, Lu Gao, Kelly M. Bakulski, Alexei Novoloaca, Catherine Allard, Irene Pappa, Maria Llambrich, Marta Vives, Dereje D. Jima, Tuomas Kvist, Andrea Baccarelli, Cory White, Faisal I. Rezwan, Gemma C. Sharp, Gwen Tindula, Anna Bergström, Veit Grote, John F. Dou, Elena Isaevska, Maria C. Magnus, Eva Corpeleijn, Patrice Perron, Vincent W.V. Jaddoe, Ellen A. Nohr, Lea Maitre, Maria Foraster, Cathrine Hoyo, Siri E. Håberg, Jari Lahti, Dawn L. DeMeo, Hongmei Zhang, Wilfried Karmaus, Inger Kull, Berthold Koletzko, Jason I. Feinberg, Luigi Gagliardi, Luigi Bouchard, Cecilia Høst Ramlau-Hansen, Henning Tiemeier, Gillian Santorelli, Rachel L. Maguire, Darina Czamara, Augusto A. Litonjua, Jean-Paul Langhendries, Michelle Plusquin, Johanna Lepeule, Elisabeth B. Binder, Elvira Verduci, Terence Dwyer, Ángel Carracedo, Natalia Ferre, Brenda Eskenazi, Manolis Kogevinas, Tim S. Nawrot, Monica C. Munthe-Kaas, Zdenko Herceg, Caroline Relton, Erik Melén, Dariusz Gruszfeld, Carrie Breton, M.D. Fallin, Akram Ghantous, Wenche Nystad, Barbara Heude, Harold Snieder, Marie-France Hivert, Janine F. Felix, Thorkild I.A. Sørensen, Mariona Bustamante, Susan K. Murphy, Katri Raikkönen, Emily Oken, John W. Holloway, Syed Hasan Arshad, Stephanie J. London, Nina Holland
Institutions: University of California, Berkeley, University of Bristol, MRC Integrative Epidemiology Unit, University Medical Center Groningen, University of Groningen, Universitat Pompeu Fabra, Barcelona Institute for Global Health, Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública, National Institute of Environmental Health Sciences, Oslo University Hospital, Norwegian Institute of Public Health, Region Stockholm, Karolinska Institutet, LMU Klinikum, Ludwig-Maximilians-Universität München, University of Southern California, University of Michigan, Centre international de recherche sur le cancer, Centre de recherche du CHUS, Erasmus MC, Erasmus MC - Sophia Children’s Hospital, Barcelona Institute of Science and Technology, Centre for Genomic Regulation, North Carolina State University, University of Helsinki, Columbia University, Merck & Co., Inc., Rahway, NJ, USA (United States), Aberystwyth University, Southampton General Hospital, University of Southampton, Cranfield University, University of Turin, Université de Sherbrooke, University of Southern Denmark, University of South-Eastern Norway, Universitat Ramon Llull, Brigham and Women's Hospital, Harvard University, University of Memphis, Stockholm South General Hospital, Sachs' Children and Youth Hospital, Johns Hopkins University, Ospedale Versilia, Azienda USL Toscana Nord Ovest, Centre Intégré Universitaire de Santé et de Services Sociaux du Saguenay–Lac-Saint-Jean, Hôpital de Chicoutimi, Aarhus University, Bradford Royal Infirmary, Bradford Institute for Health Research, Duke University, Duke Medical Center, Max Planck Institute of Psychiatry, University of Rochester Medicine, University of Rochester, Groupe santé CHC, Hasselt University, Centre National de la Recherche Scientifique, Inserm, Institut pour l'avancée des biosciences, Université Grenoble Alpes, Emory University, University of Milan, Ospedale dei Bambini Vittore Buzzi, The University of Melbourne, University of Oxford, Murdoch Children's Research Institute, Universidade de Santiago de Compostela, Centre for Biomedical Network Research on Rare Diseases, Fundación Pública Galega de Medicina Xenómica, Instituto de Investigación Sanitaria de Santiago, Servicio Gallego de Salud, Institut de Recerca Biomèdica Catalunya Sud, Universitat Rovira i Virgili, Municipal Institute for Medical Research, Hospital del Mar Research Institute, KU Leuven, Children's Memorial Health Institute, Université Paris Cité, Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement, Equipe de Recherche en Epidémiologie Nutritionnelle, Centre de Recherche Épidémiologie et Statistique, Massachusetts General Hospital, Harvard Pilgrim Health Care, University of Copenhagen, Novo Nordisk Foundation Center for Basic Metabolic Research, David Hide Asthma and Allergy Research Centre
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,980
Awards: Prenatal influences on childhood health: what role for mums and dads?, NutriPROGRAM: Early-life Nutritional Programming of Metabolic Health through Epigenetic Pathways, Follow-up and Maintenance of the Newborn Epigenetics STudy (NEST) Cohort, Genetic And Environmental Factors In Childhood Respiratory Health, Genetic Analyses For Epidemiologic Studies Of Respiratory Disease, Environmental Agents as Modulators of Disease Processes, Michigan Center on Lifestage Environmental Exposures and Disease (M-LEEaD)
OpenAlex ID: W4220682584