Maternal asthma and newborn DNA methylation

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

doi:10.1186/s13148-025-01858-4

Maternal asthma and newborn DNA methylation

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 ArshadJohn 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^*

^*Corresponding author for this work

Department of Computer Science

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Article number	79
Number of pages	14
Journal	Clinical Epigenetics
Volume	17
Early online date	10 May 2025
DOIs	https://doi.org/10.1186/s13148-025-01858-4
Publication status	E-pub ahead of print - 10 May 2025

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Pedersen, C. E. T., Hoang, T. T., Jin, J., Starnawska, A., Granell, R., Elliott, H. R., Huels, A., Zar, H. J., Stein, D. J., Zhang, Y., Dekker, H. T. D., Duijts, L., Felix, J. F., Sangüesa, J., Bustamante, M., Casas, M., Vrijheid, M., Kadalayil, L., Rezwan, F. I., ... Bønnelykke, K. (2025). Maternal asthma and newborn DNA methylation. Clinical Epigenetics, 17, Article 79. Advance online publication. https://doi.org/10.1186/s13148-025-01858-4

@article{f8f5b894b0d241cea1fd4d1ee3cd0d3c,

title = "Maternal asthma and newborn DNA methylation",

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.",

author = "Pedersen, \{Casper Emil Tingskov\} and Hoang, \{Thanh T.\} and Jianping Jin and Anna Starnawska and Raquel Granell and Elliott, \{Hannah R.\} and Anke Huels and Zar, \{Heather J.\} and Stein, \{Dan J.\} and Yining Zhang and Dekker, \{Herman T.den\} and Liesbeth Duijts and Felix, \{Janine F.\} and J{\'u}lia Sang{\"u}esa and Mariona Bustamante and Maribel Casas and Martine Vrijheid and Latha Kadalayil and Rezwan, \{Faisal I.\} and Hasan Arshad and Holloway, \{John W.\} and Stefan R{\"o}der and Zenclussen, \{Ana C.\} and Gunda Herberth and Staunstrup, \{Nicklas Heine\} and Horsdal, \{Henriette Thisted\} and Jonathan Mill and Eilis Hannon and \{iPSYCH-MINERvA Group\} and Isabella Annesi-Maesano and Giancarlo Pesce and Nour Ba{\"i}z and Barbara Heude and Sahra Hosseinian-Mohazzab and Breton, \{Carrie V.\} and Sophia Harlid and Justin Harbs and Magnus Domellof and Christina West and Edwina Yeung and Xuehuo Zeng and Wenche Nystad and H{\aa}berg, \{Siri E.\} and Magnus, \{Maria C.\} and Diana Schendel and London, \{Stephanie J.\} and Klaus B{\o}nnelykke",

note = "Publisher Copyright: {\textcopyright} This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2025.",

year = "2025",

month = may,

day = "10",

doi = "10.1186/s13148-025-01858-4",

language = "English",

volume = "17",

journal = "Clinical Epigenetics",

issn = "1868-7075",

publisher = "Springer Nature",

}

Pedersen, CET, Hoang, TT, Jin, J, Starnawska, A, Granell, R, Elliott, HR, Huels, A, Zar, HJ, Stein, DJ, Zhang, Y, Dekker, HTD, Duijts, L, Felix, JF, Sangüesa, J, Bustamante, M, Casas, M, Vrijheid, M, Kadalayil, L, Rezwan, FI, Arshad, H, Holloway, JW, Röder, S, Zenclussen, AC, Herberth, G, Staunstrup, NH, Horsdal, HT, Mill, J, Hannon, E, iPSYCH-MINERvA Group, Annesi-Maesano, I, Pesce, G, Baïz, N, Heude, B, Hosseinian-Mohazzab, S, Breton, CV, Harlid, S, Harbs, J, Domellof, M, West, C, Yeung, E, Zeng, X, Nystad, W, Håberg, SE, Magnus, MC, Schendel, D, London, SJ & Bønnelykke, K 2025, 'Maternal asthma and newborn DNA methylation', Clinical Epigenetics, vol. 17, 79. https://doi.org/10.1186/s13148-025-01858-4

TY - JOUR

T1 - Maternal asthma and newborn DNA methylation

AU - Pedersen, Casper Emil Tingskov

AU - Hoang, Thanh T.

AU - Jin, Jianping

AU - Starnawska, Anna

AU - Granell, Raquel

AU - Elliott, Hannah R.

AU - Huels, Anke

AU - Zar, Heather J.

AU - Stein, Dan J.

AU - Zhang, Yining

AU - Dekker, Herman T.den

AU - Duijts, Liesbeth

AU - Felix, Janine F.

AU - Sangüesa, Júlia

AU - Bustamante, Mariona

AU - Casas, Maribel

AU - Vrijheid, Martine

AU - Kadalayil, Latha

AU - Rezwan, Faisal I.

AU - Arshad, Hasan

AU - Holloway, John W.

AU - Röder, Stefan

AU - Zenclussen, Ana C.

AU - Herberth, Gunda

AU - Staunstrup, Nicklas Heine

AU - Horsdal, Henriette Thisted

AU - Mill, Jonathan

AU - Hannon, Eilis

AU - iPSYCH-MINERvA Group

AU - Annesi-Maesano, Isabella

AU - Pesce, Giancarlo

AU - Baïz, Nour

AU - Heude, Barbara

AU - Hosseinian-Mohazzab, Sahra

AU - Breton, Carrie V.

AU - Harlid, Sophia

AU - Harbs, Justin

AU - Domellof, Magnus

AU - West, Christina

AU - Yeung, Edwina

AU - Zeng, Xuehuo

AU - Nystad, Wenche

AU - Håberg, Siri E.

AU - Magnus, Maria C.

AU - Schendel, Diana

AU - London, Stephanie J.

AU - Bønnelykke, Klaus

PY - 2025/5/10

Y1 - 2025/5/10

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=105004887387&partnerID=8YFLogxK

U2 - 10.1186/s13148-025-01858-4

DO - 10.1186/s13148-025-01858-4

M3 - Article

C2 - 40349045

AN - SCOPUS:105004887387

SN - 1868-7075

VL - 17

JO - Clinical Epigenetics

JF - Clinical Epigenetics

M1 - 79

ER -

Maternal asthma and newborn DNA methylation

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