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Maternal asthma and newborn DNA methylation

Maternal asthma and newborn DNA methylation
Maternal asthma and newborn DNA methylation

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.

Adult, Asthma/genetics, CpG Islands, DNA Methylation, Epigenesis, Genetic, Female, Genome-Wide Association Study/methods, Humans, Infant, Newborn, Male, Pregnancy, Pregnancy Complications/genetics, Prenatal Exposure Delayed Effects/genetics
1868-7075
Pedersen, Casper-Emil Tingskov
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Hoang, Thanh T
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Jin, Jianping
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Starnawska, Anna
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Granell, Raquel
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Elliott, Hannah R
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Huels, Anke
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Zar, Heather J
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Stein, Dan J
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Zhang, Yining
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Dekker, Herman T den
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Duijts, Liesbeth
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Felix, Janine F
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Sangüesa, Júlia
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Bustamante, Mariona
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Casas, Maribel
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Vrijheid, Martine
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Kadalayil, Latha
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Rezwan, Faisal I
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Arshad, Hasan
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Holloway, John W
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Röder, Stefan
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Zenclussen, Ana C
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Herberth, Gunda
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Staunstrup, Nicklas Heine
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Horsdal, Henriette Thisted
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Mill, Jonathan
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Hannon, Eilis
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Annesi-Maesano, Isabella
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Pesce, Giancarlo
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Baïz, Nour
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Heude, Barbara
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Hosseinian-Mohazzab, Sahra
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Breton, Carrie V
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Harlid, Sophia
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Harbs, Justin
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Domellof, Magnus
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West, Christina
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Yeung, Edwina
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Zeng, Xuehuo
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Nystad, Wenche
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Håberg, Siri E
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Magnus, Maria C
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Schendel, Diana
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London, Stephanie J
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Bønnelykke, Klaus
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iPSYCH-MINERvA Group
Pedersen, Casper-Emil Tingskov
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Hoang, Thanh T
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Jin, Jianping
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Starnawska, Anna
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Granell, Raquel
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Elliott, Hannah R
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Huels, Anke
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Zar, Heather J
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Stein, Dan J
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Zhang, Yining
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Dekker, Herman T den
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Duijts, Liesbeth
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Felix, Janine F
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Sangüesa, Júlia
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Bustamante, Mariona
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Casas, Maribel
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Vrijheid, Martine
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Kadalayil, Latha
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Rezwan, Faisal I
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Arshad, Hasan
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Holloway, John W
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Röder, Stefan
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Zenclussen, Ana C
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Herberth, Gunda
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Staunstrup, Nicklas Heine
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Horsdal, Henriette Thisted
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Mill, Jonathan
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Hannon, Eilis
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Annesi-Maesano, Isabella
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Pesce, Giancarlo
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Baïz, Nour
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Heude, Barbara
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Hosseinian-Mohazzab, Sahra
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Breton, Carrie V
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Harlid, Sophia
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Harbs, Justin
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Domellof, Magnus
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West, Christina
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Yeung, Edwina
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Zeng, Xuehuo
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Nystad, Wenche
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Håberg, Siri E
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Magnus, Maria C
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Schendel, Diana
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London, Stephanie J
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Bønnelykke, Klaus
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Pedersen, Casper-Emil Tingskov, Hoang, Thanh T and Jin, Jianping , iPSYCH-MINERvA Group (2025) Maternal asthma and newborn DNA methylation. Clinical Epigenetics, 17 (1), [79]. (doi:10.1186/s13148-025-01858-4).

Record type: Article

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.

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s13148-025-01858-4 - Version of Record
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Accepted/In Press date: 11 March 2025
Published date: 10 May 2025
Keywords: Adult, Asthma/genetics, CpG Islands, DNA Methylation, Epigenesis, Genetic, Female, Genome-Wide Association Study/methods, Humans, Infant, Newborn, Male, Pregnancy, Pregnancy Complications/genetics, Prenatal Exposure Delayed Effects/genetics

Identifiers

Local EPrints ID: 502777
URI: http://eprints.soton.ac.uk/id/eprint/502777
DOI: doi:10.1186/s13148-025-01858-4
ISSN: 1868-7075
PURE UUID: 86f68c74-b97f-45be-9c28-04607fe2fb3d
ORCID for Faisal I Rezwan: ORCID iD orcid.org/0000-0001-9921-222X
ORCID for John W Holloway: ORCID iD orcid.org/0000-0001-9998-0464

Catalogue record

Date deposited: 08 Jul 2025 16:36
Last modified: 11 Sep 2025 02:39

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Contributors

Author: Casper-Emil Tingskov Pedersen
Author: Thanh T Hoang
Author: Jianping Jin
Author: Anna Starnawska
Author: Raquel Granell
Author: Hannah R Elliott
Author: Anke Huels
Author: Heather J Zar
Author: Dan J Stein
Author: Yining Zhang
Author: Herman T den Dekker
Author: Liesbeth Duijts
Author: Janine F Felix
Author: Júlia Sangüesa
Author: Mariona Bustamante
Author: Maribel Casas
Author: Martine Vrijheid
Author: Latha Kadalayil
Author: Faisal I Rezwan ORCID iD
Author: Hasan Arshad
Author: John W Holloway ORCID iD
Author: Stefan Röder
Author: Ana C Zenclussen
Author: Gunda Herberth
Author: Nicklas Heine Staunstrup
Author: Henriette Thisted Horsdal
Author: Jonathan Mill
Author: Eilis Hannon
Author: Isabella Annesi-Maesano
Author: Giancarlo Pesce
Author: Nour Baïz
Author: Barbara Heude
Author: Sahra Hosseinian-Mohazzab
Author: Carrie V Breton
Author: Sophia Harlid
Author: Justin Harbs
Author: Magnus Domellof
Author: Christina West
Author: Edwina Yeung
Author: Xuehuo Zeng
Author: Wenche Nystad
Author: Siri E Håberg
Author: Maria C Magnus
Author: Diana Schendel
Author: Stephanie J London
Author: Klaus Bønnelykke
Corporate Author: iPSYCH-MINERvA Group

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