Pedersen Casper-Emil Tingskov, Hoang Thanh T, Jin Jianping, Starnawska Anna, Granell Raquel, Elliott Hannah R, Huels Anke, Zar Heather J, Stein Dan J, Zhang Yining, Dekker Herman T den, Duijts Liesbeth, Felix Janine F, Sangüesa Júlia, Bustamante Mariona, Casas Maribel, Vrijheid Martine, Kadalayil Latha, Rezwan Faisal I, Arshad Hasan, Holloway John W, Röder Stefan, Zenclussen Ana C, Herberth Gunda, Staunstrup Nicklas Heine, Horsdal Henriette Thisted, Mill Jonathan, Hannon Eilis, Annesi-Maesano Isabella, Pesce Giancarlo, Baïz Nour, Heude Barbara, Hosseinian-Mohazzab Sahra, Breton Carrie V, Harlid Sophia, Harbs Justin, Domellof Magnus, West Christina, Yeung Edwina, Zeng Xuehuo, Nystad Wenche, Håberg Siri E, Magnus Maria C, Schendel Diana, London Stephanie J, Bønnelykke Klaus
Copenhagen Prospective Studies On Asthma in Childhood, Herlev and Gentofte Hospital, COPSAC, University of Copenhagen, Ledreborg Alle 34 Gentofte, 2820, Copenhagen, Denmark.
Division of Intramural Research, National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), MD A3-05, PO 12233, Research Triangle Park, NC, 27709, USA.
Clin Epigenetics. 2025 May 10;17(1):79. doi: 10.1186/s13148-025-01858-4.
Prenatal exposure to maternal asthma may influence DNA methylation patterns in offspring, potentially affecting their susceptibility to later diseases including asthma.
To investigate the relationship between parental asthma and newborn blood DNA methylation.
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.
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.
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.
产前暴露于母亲哮喘可能会影响后代的DNA甲基化模式，潜在地影响他们对包括哮喘在内的后续疾病的易感性。
研究父母哮喘与新生儿血液DNA甲基化之间的关系。
对13个队列中的7433名新生儿进行全基因组关联分析，这些新生儿具有来自Illumina450K或EPIC阵列的血液甲基化数据。我们使用固定效应荟萃分析来识别差异甲基化的CpG（DMC），并使用comb-p来识别与孕期母亲哮喘和既往母亲哮喘相关的差异甲基化区域（DMR）。对父亲哮喘进行分析以作比较。模型针对协变量和细胞类型组成进行了调整。我们在公开可用的儿童血液和成人肺数据中检查了相关位点是否与基因表达分析有关。
我们在错误发现率<0.05时鉴定出27个与孕期母亲哮喘相关的CpG，但未发现与既往母亲哮喘相关的CpG。有两个不同的CpG与父亲哮喘相关。我们观察到5个与孕期母亲哮喘相关的DMR，3个与既往母亲哮喘相关的DMR，以及13个与父亲哮喘相关的DMR。使用832名儿童的血液数据和424名成人的肺数据进行的基因表达分析表明，使用母亲哮喘鉴定出的DMC与包括HLA基因和HOXA5在内的几个基因的表达之间存在关联，这些基因先前与哮喘或肺功能有关。
父母哮喘，尤其是孕期母亲哮喘，可能与新生儿DNA甲基化的改变有关。这些发现可能有助于揭示哮喘易感性的潜在机制。
