Molecular networks in atopic mothers impact the risk of infant atopy

Michaela Schedel; Sonia M Leach; Matthew J Strand; Thomas Danhorn; Morgan MacBeth; Anna V Faino; Anne M Lynch; Virginia D Winn; Lindsay L Munoz; Shannon M Forsberg; David A Schwartz; Erwin W Gelfand; Pia J Hauk

doi:10.1111/all.15490

Molecular networks in atopic mothers impact the risk of infant atopy

Allergy. 2023 Jan;78(1):244-257. doi: 10.1111/all.15490. Epub 2022 Sep 4.

Authors

Michaela Schedel^{1

2

3}, Sonia M Leach^{4

5}, Matthew J Strand⁶, Thomas Danhorn^{6

7}, Morgan MacBeth^{1

8}, Anna V Faino^{6

9}, Anne M Lynch^{10

11}, Virginia D Winn^{11

12}, Lindsay L Munoz^{1

11}, Shannon M Forsberg^{1

13}, David A Schwartz¹⁴, Erwin W Gelfand¹, Pia J Hauk^{1

15}

Affiliations

¹ Divisions of Allergy and Immunology and Cell Biology, Department of Pediatrics, National Jewish Health, Denver, Colorado, USA.
² Department of Pulmonary Medicine, University Medicine Essen-Ruhrlandklinik, Essen, Germany.
³ Department of Pulmonary Medicine, University Medicine Essen, University Hospital, Essen, Germany.
⁴ Department of Biomedical Research, National Jewish Health, Denver, Colorado, USA.
⁵ Center for Genes, Environment & Health, National Jewish Health, Denver, Colorado, USA.
⁶ Division of Biostatistics and Bioinformatics, National Jewish Health, Denver, Colorado, USA.
⁷ Department of Pharmacology, School of Medicine, University of Colorado, Aurora, Colorado, USA.
⁸ Department of Medical Oncology, School of Medicine, University of Colorado, Aurora, Colorado, USA.
⁹ Biostatistics, Epidemiology and Research Core, Seattle Children's Research Institute, Seattle, Washington, USA.
¹⁰ Department of Ophthalmology, School of Medicine, University of Colorado, Aurora, Colorado, USA.
¹¹ Department of Obstetrics and Gynecology, School of Medicine, University of Colorado, Aurora, Colorado, USA.
¹² Department of Obstetrics and Gynecology, Stanford University, Stanford, California, USA.
¹³ Department of Thoracic Oncology, University of Colorado Cancer Center, University of Colorado, Aurora, Colorado, USA.
¹⁴ Department of Medicine, School of Medicine, University of Colorado, Aurora, Colorado, USA.
¹⁵ Section Allergy/Immunology, Children's Hospital Colorado, University of Colorado, Aurora, Colorado, USA.

PMID: 35993851
DOI: 10.1111/all.15490

Abstract

Background: The prevalence of atopic diseases has increased with atopic dermatitis (AD) as the earliest manifestation. We assessed if molecular risk factors in atopic mothers influence their infants' susceptibility to an atopic disease.

Methods: Pregnant women and their infants with (n = 174, high-risk) or without (n = 126, low-risk) parental atopy were enrolled in a prospective birth cohort. Global differentially methylated regions (DMRs) were determined in atopic (n = 92) and non-atopic (n = 82) mothers. Principal component analysis was used to predict atopy risk in children dependent on maternal atopy. Genome-wide transcriptomic analyses were performed in paired atopic (n = 20) and non-atopic (n = 15) mothers and cord blood. Integrative genomic analyses were conducted to define methylation-gene expression relationships.

Results: Atopic dermatitis was more prevalent in high-risk compared to low-risk children by age 2. Differential methylation analyses identified 165 DMRs distinguishing atopic from non-atopic mothers. Inclusion of DMRs in addition to maternal atopy significantly increased the odds ratio to develop AD in children from 2.56 to 4.26. In atopic compared to non-atopic mothers, 139 differentially expressed genes (DEGs) were identified significantly enriched of genes within the interferon signaling pathway. Expression quantitative trait methylation analyses dependent on maternal atopy identified 29 DEGs controlled by 136 trans-acting methylation marks, some located near transcription factors. Differential expression for the same nine genes, including MX1 and IFI6 within the interferon pathway, was identified in atopic and non-atopic mothers and high-risk and low-risk children.

Conclusion: These data suggest that in utero epigenetic and transcriptomic mechanisms predominantly involving the interferon pathway may impact and predict the development of infant atopy.

Keywords: atopic dermatitis; cord blood; differentially expressed gene; differentially methylated region; maternal atopy.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Child
Child, Preschool
Dermatitis, Atopic* / epidemiology
Dermatitis, Atopic* / genetics
Family
Female
Humans
Infant
Pregnancy
Prospective Studies
Risk Factors
Transcriptome

Grants and funding

RC1 HD063508/HD/NICHD NIH HHS/United States