. 2025 May 10;17(1):79.

doi: 10.1186/s13148-025-01858-4.

Maternal asthma and newborn DNA methylation

Casper-Emil Tingskov Pedersen¹, Thanh T Hoang^{2

3

4

5}, Jianping Jin², Anna Starnawska^{6

7

8}, Raquel Granell^{9

10}, Hannah R Elliott^{9

10}, Anke Huels^{11

12

13}, Heather J Zar¹⁴, Dan J Stein¹⁴, Yining Zhang¹¹, Herman T den Dekker¹⁵, Liesbeth Duijts^{15

16}, Janine F Felix¹⁵, Júlia Sangüesa¹⁷, Mariona Bustamante¹⁷, Maribel Casas¹⁷, Martine Vrijheid^{17

18

19}, Latha Kadalayil²⁰, Faisal I Rezwan^{21

22}, Hasan Arshad^{23

24

25}, John W Holloway^{22

25}, Stefan Röder²⁶, Ana C Zenclussen²⁶, Gunda Herberth²⁶, Nicklas Heine Staunstrup^{6

7

8}, Henriette Thisted Horsdal^{7

27}, Jonathan Mill²⁸, Eilis Hannon²⁸; iPSYCH-MINERvA Group; Isabella Annesi-Maesano²⁹, Giancarlo Pesce²⁹, Nour Baïz²⁹, Barbara Heude³⁰, Sahra Hosseinian-Mohazzab³¹, Carrie V Breton³¹, Sophia Harlid³², Justin Harbs³², Magnus Domellof³³, Christina West³³, Edwina Yeung³⁴, Xuehuo Zeng³⁵, Wenche Nystad³⁶, Siri E Håberg³⁷, Maria C Magnus^{9

37

38}, Diana Schendel^{7

27

39}, Stephanie J London^#⁴⁰, Klaus Bønnelykke^#⁴¹

Affiliations

¹ Copenhagen Prospective Studies On Asthma in Childhood, Herlev and Gentofte Hospital, COPSAC, University of Copenhagen, Ledreborg Alle 34 Gentofte, 2820, Copenhagen, Denmark.
² 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.
³ Department of Pediatrics, Division of Hematology-Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
⁴ Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA.
⁵ Cancer and Hematology Center, Texas Children's Hospital, Houston, TX, USA.
⁶ Department of Biomedicine, Aarhus University, 8000, Aarhus, Denmark.
⁷ The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark.
⁸ Center for Genomics and Personalized Medicine, CGPM, and Center for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark.
⁹ Department of Population Health Sciences, Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, Bristol, BS8 2BN, UK.
¹⁰ Medical Research Council Integrative Epidemiology Unit at the University of Bristol, Bristol, BS8 2BN, UK.
¹¹ Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
¹² Ganagarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
¹³ Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
¹⁴ SAMRC Unit On Child & Adolescent Health, Dept of Paediatrics, University of Cape Town, Cape Town, South Africa.
¹⁵ The Generation R Study Group and Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
¹⁶ Department of Neonatal and Pedicatric Intensive Care, Division of Neonatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
¹⁷ ISGlobal, Barcelona, Spain.
¹⁸ Universitat Pompeu Fabra (UPF), Barcelona, Spain.
¹⁹ CIBER Epidemiología y Salud Pública, Madrid, Spain.
²⁰ School of Chemistry, Faculty of Engineering and Physical Sciences, University of Southampton, Southampton, UK.
²¹ Department of Computer Science, Aberystwyth University, University, Aberystwyth, SY23 3DB, UK.
²² Faculty of Medicine, Human Development and Health, University of Southampton, Southampton, UK.
²³ David Hide Asthma and Allergy Research Centre, Isle of Wight, UK.
²⁴ Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.
²⁵ NIHR Southampton Biomedical Research Centre, Southampton General Hospital, Southampton, UK.
²⁶ Department of Environmental Immunology, Helmholtz Centre for Environmental Research-UFZ, Leipzig, Germany.
²⁷ National Centre for Register-Based Research, Aarhus University, Aarhus, Denmark.
²⁸ Department of Clinical & Biomedical Sciences, University of Exeter Medical School, University of Exeter, Exeter, UK.
²⁹ Institute Desbrest of Epidemiology and Public Health, University of Montpellier and INSERM, Montpellier, France.
³⁰ Inserm, INRAE, Center for Research in Epidemiology and StatisticS (CRESS), Université Paris Cité and Université Sorbonne Paris Nord, 75004, Paris, France.
³¹ Department of Population and Public Health Sciences, University of Southern California, Los Angeles, CA, USA.
³² Department of Diagnostics and Intervention, Oncology, Umeå University, Umeå, Sweden.
³³ Department of Clinical Sciences, Pediatrics, Umeå University, Umeå, Sweden.
³⁴ Epidemiology Branch, Division of Population Health Research, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, 20817, USA.
³⁵ Glotech Inc., 1801 Research Blvd #605, Rockville, MD, 20850, USA.
³⁶ Department of Chronic Diseases, Division of Mental and Physical Health, Norwegian Institute of Public Health, Oslo, Norway.
³⁷ Centre for Fertility and Health, Norwegian Institute of Public Health, Skøyen, P.O. Box 222, 0213, Oslo, Norway.
³⁸ MRC Integrative Epidemiology Unit at the University of Bristol, Oakfield House, Oakfield Grove, Bristol, BS8 2BN, UK.
³⁹ AJ Drexel Autism Institute, Drexel University, Philadelphia, USA.
⁴⁰ 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. london2@niehs.nih.gov.
⁴¹ Copenhagen Prospective Studies On Asthma in Childhood, Herlev and Gentofte Hospital, COPSAC, University of Copenhagen, Ledreborg Alle 34 Gentofte, 2820, Copenhagen, Denmark. kb@copsac.com.

^# Contributed equally.

PMID: 40349045
PMCID: PMC12065361
DOI: 10.1186/s13148-025-01858-4

Maternal asthma and newborn DNA methylation

Casper-Emil Tingskov Pedersen et al. Clin Epigenetics. 2025.

. 2025 May 10;17(1):79.

doi: 10.1186/s13148-025-01858-4.

Authors

Affiliations

¹ Copenhagen Prospective Studies On Asthma in Childhood, Herlev and Gentofte Hospital, COPSAC, University of Copenhagen, Ledreborg Alle 34 Gentofte, 2820, Copenhagen, Denmark.
² 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.
³ Department of Pediatrics, Division of Hematology-Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
⁴ Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA.
⁵ Cancer and Hematology Center, Texas Children's Hospital, Houston, TX, USA.
⁶ Department of Biomedicine, Aarhus University, 8000, Aarhus, Denmark.
⁷ The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark.
⁸ Center for Genomics and Personalized Medicine, CGPM, and Center for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark.
⁹ Department of Population Health Sciences, Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, Bristol, BS8 2BN, UK.
¹⁰ Medical Research Council Integrative Epidemiology Unit at the University of Bristol, Bristol, BS8 2BN, UK.
¹¹ Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
¹² Ganagarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
¹³ Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
¹⁴ SAMRC Unit On Child & Adolescent Health, Dept of Paediatrics, University of Cape Town, Cape Town, South Africa.
¹⁵ The Generation R Study Group and Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
¹⁶ Department of Neonatal and Pedicatric Intensive Care, Division of Neonatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
¹⁷ ISGlobal, Barcelona, Spain.
¹⁸ Universitat Pompeu Fabra (UPF), Barcelona, Spain.
¹⁹ CIBER Epidemiología y Salud Pública, Madrid, Spain.
²⁰ School of Chemistry, Faculty of Engineering and Physical Sciences, University of Southampton, Southampton, UK.
²¹ Department of Computer Science, Aberystwyth University, University, Aberystwyth, SY23 3DB, UK.
²² Faculty of Medicine, Human Development and Health, University of Southampton, Southampton, UK.
²³ David Hide Asthma and Allergy Research Centre, Isle of Wight, UK.
²⁴ Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.
²⁵ NIHR Southampton Biomedical Research Centre, Southampton General Hospital, Southampton, UK.
²⁶ Department of Environmental Immunology, Helmholtz Centre for Environmental Research-UFZ, Leipzig, Germany.
²⁷ National Centre for Register-Based Research, Aarhus University, Aarhus, Denmark.
²⁸ Department of Clinical & Biomedical Sciences, University of Exeter Medical School, University of Exeter, Exeter, UK.
²⁹ Institute Desbrest of Epidemiology and Public Health, University of Montpellier and INSERM, Montpellier, France.
³⁰ Inserm, INRAE, Center for Research in Epidemiology and StatisticS (CRESS), Université Paris Cité and Université Sorbonne Paris Nord, 75004, Paris, France.
³¹ Department of Population and Public Health Sciences, University of Southern California, Los Angeles, CA, USA.
³² Department of Diagnostics and Intervention, Oncology, Umeå University, Umeå, Sweden.
³³ Department of Clinical Sciences, Pediatrics, Umeå University, Umeå, Sweden.
³⁴ Epidemiology Branch, Division of Population Health Research, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, 20817, USA.
³⁵ Glotech Inc., 1801 Research Blvd #605, Rockville, MD, 20850, USA.
³⁶ Department of Chronic Diseases, Division of Mental and Physical Health, Norwegian Institute of Public Health, Oslo, Norway.
³⁷ Centre for Fertility and Health, Norwegian Institute of Public Health, Skøyen, P.O. Box 222, 0213, Oslo, Norway.
³⁸ MRC Integrative Epidemiology Unit at the University of Bristol, Oakfield House, Oakfield Grove, Bristol, BS8 2BN, UK.
³⁹ AJ Drexel Autism Institute, Drexel University, Philadelphia, USA.
⁴⁰ 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. london2@niehs.nih.gov.
⁴¹ Copenhagen Prospective Studies On Asthma in Childhood, Herlev and Gentofte Hospital, COPSAC, University of Copenhagen, Ledreborg Alle 34 Gentofte, 2820, Copenhagen, Denmark. kb@copsac.com.

^# Contributed equally.

PMID: 40349045
PMCID: PMC12065361
DOI: 10.1186/s13148-025-01858-4

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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Conflict of interest statement

Declarations. Competing interests: All authors declare no potential, perceived or real conflict of interest regarding the content of this manuscript. The funding agencies did not have any role in design and conduct of the study; collection, management and interpretation of the data; or preparation, review or approval of the manuscript. No pharmaceutical company was involved in the study.

Figures

**Fig. 1**
Flowchart describing the number of samples, the primary quality control filters as well as the analyses included

**Fig. 2**
Manhattan plot of epigenome-wide association of maternal asthma during pregnancy and offspring methylation. Models include the following covariates: child sex, maternal smoking during pregnancy, gestational age, mode of delivery, maternal age at childbirth, maternal socioeconomic status, estimated cell type, batch covariates and ancestry. Panel A) shows analysis restricted to 435,329 probes on the 450 K chip for 7 cohorts using 202 exposed and 2946 non-exposed individuals (lambda = 1.09), and panel B) shows 321,034 probes exclusive to the EPIC chip for 2 cohorts using 76 exposed and 675 non-exposed individuals (lambda = 1.18). The red line indicates 5% FDR significance

**Fig. 3**
Spearman correlations of effects from meta-analyses of all included models for A) CpGs pertaining to the overlap between the 450 K and EPIC chip and B) the CpGs unique to the EPIC chip. MAP, maternal asthma during pregnancy; MAE, maternal asthma ever while; PAE, paternal asthma ever. Sex-stratified models are defined by suffixes. ‘Int’ represent interaction models testing for differences between the sexes

See this image and copyright information in PMC

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Maternal asthma and newborn DNA methylation

Affiliations

Maternal asthma and newborn DNA methylation

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Research Materials