Year: 2025
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Prenatal exposure to maternal asthma may influence DNA methylation patterns in offspring, potentially affecting their susceptibility to later diseases including asthma. OBJECTIVE: To investigate the relationship between parental asthma and newborn blood DNA methylation. METHODS: Epigenome-wide association analyses were conducted in 13 cohorts on 7433 newborns with blood methylation data from the Illumina450K or EPIC array. We used fixed effects meta-analyses to identify differentially methylated CpGs (DMCs) and comb-p to identify differentially methylated regions (DMRs) associated with maternal asthma during pregnancy and maternal asthma ever. Paternal asthma was analyzed for comparison. Models were adjusted for covariates and cell-type composition. We examined whether implicated sites related to gene expression analyses in publicly available data for childhood blood and adult lung. RESULTS: We identified 27 CpGs associated with maternal asthma during pregnancy at False Discovery Rate < 0.05 but none for maternal asthma ever. Two distinct CpGs were associated with paternal asthma. We observed 5 DMRs associated with maternal asthma during pregnancy 3 associated with maternal asthma ever and 13 DMRs associated with paternal asthma. Gene expression analysis using data in blood from 832 children and lung from 424 adults showed associations between identified DMCs using maternal asthma and expression of several genes, including HLA genes and HOXA5, previously implicated in asthma or lung function. CONCLUSION: Parental asthma, especially maternal asthma during pregnancy, may be associated with alterations in newborn DNA methylation. These findings might shed light on underlying mechanisms for asthma susceptibility.
Source: Clinical Epigenetics
Authors: Casper-Emil Tingskov Pedersen, Thanh T. Hoang, Jianping Jin, Anna Starnawska, Raquel Granell, Hannah R. Elliott, Anke Huels, Heather J. Zar, Dan J. Stein, Yining Zhang, Herman T. den Dekker, Liesbeth Duijts, Janine F. Felix, Júlia Sangüesa, Mariona Bustamante, Maribel Casas, Martine Vrijheid, Latha Kadalayil, Faisal I. Rezwan, Hasan Arshad, John W. Holloway, Stefan Röder, Ana C. Zenclussen, Gunda Herberth, Nicklas Heine Staunstrup, Henriette Thisted Horsdal, Jonathan Mill, Eilis Hannon, iPSYCH-MINERvA Group, Isabella Annesi-Maesano, Giancarlo Pesce, Nour Baïz, Barbara Heude, Sahra Hosseinian-Mohazzab, Carrie V. Breton, Sophia Harlid, Justin Harbs, Magnus Domellof, Christina West, Edwina Yeung, Xuehuo Zeng, Wenche Nystad, Siri E. Håberg, Maria C. Magnus, Diana Schendel, Stephanie J. London, Klaus Bønnelykke
Institutions: University of Copenhagen, Gentofte Hospital, Copenhagen Prospective Studies on Asthma in Childhood, National Institutes of Health, Baylor College of Medicine, National Institute of Environmental Health Sciences, Texas Children's Hospital, Dan L Duncan Comprehensive Cancer Center, Aarhus University, Lundbeck Foundation, University of Bristol, MRC Integrative Epidemiology Unit, Emory University, South African Medical Research Council, University of Cape Town, Erasmus MC, Erasmus University Rotterdam, Barcelona Institute for Global Health, Universitat Pompeu Fabra, Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública, University of Southampton, Aberystwyth University, Southampton General Hospital, NIHR Southampton Biomedical Research Centre, David Hide Asthma and Allergy Research Centre, Helmholtz Centre for Environmental Research, University of Exeter, Inserm, Université de Montpellier, Université Paris Cité, Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement, Université Sorbonne Paris Nord, Centre de Recherche Épidémiologie et Statistique, University of Southern California, Umeå University, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Glotech (United States), Norwegian Institute of Public Health, Drexel University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,890
Funders: Strategiske Forskningsråd, Beatrice and Samuel A. Seaver Foundation, University of Bristol, Västerbotten Läns Landsting, Lundbeckfonden, Knut och Alice Wallenbergs Stiftelse, Vetenskapsrådet, Umeå Universitet, Ministeriet Sundhed Forebyggelse, Science for Life Laboratory, National Institutes of Health, National Institute of Neurological Disorders and Stroke, National Institute of Environmental Health Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1948905973, G2340656413, G4072675998
OpenAlex ID: W4410250232