Pedersen, Casper-Emil TingskovSangüesa, JúliaBustamante Pineda, MarionaCasas Sanahuja, MaribelVrijheid, MartineBønnelykke, Klaus2025-06-232025-06-232025Pedersen CT, Hoang TT, Jin J, Starnawska A, Granell R, Elliott HR, et al. Maternal asthma and newborn DNA methylation. Clin Epigenetics. 2025 May 10;17(1):79. DOI: 10.1186/s13148-025-01858-41868-7075http://hdl.handle.net/10230/70743Background: 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.application/pdfeng© This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2025. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.AsmaADNinfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1186/s13148-025-01858-4info:eu-repo/semantics/openAccess