Publication Details

Category Text Publication
Reference Category Journals
DOI 10.1111/all.15658
Licence creative commons licence
Title (Primary) Global hypomethylation in childhood asthma identified by genome-wide DNA-methylation sequencing preferentially affects enhancer regions
Author Thürmann, L.; Klös, M.; Mackowiak, S.D.; Bieg, M.; Bauer, T.; Ishaque, N.; Messingschlager, M.; Herrmann, C.; Röder, S. ORCID logo ; Bauer, M.; Schäuble, S.; Faessler, E.; Hahn, U.; Weichenhan, D.; Mücke, O.; Plass, C.; Borte, M.; von Mutius, E.; Stangl, G.I.; Lauener, R.; Karvonen, A.M.; Divaret-Chauveau, A.; Riedler, J.; Heinrich, J.; Standl, M.; von Berg, A.; Schaaf, B.; Herberth, G. ORCID logo ; Kabesch, M.; Eils, R.; Trump, S.; Lehmann, I.
Source Titel Allergy
Year 2023
Department IMMU
Volume 78
Issue 6
Page From 1489
Page To 1506
Language englisch
Topic T9 Healthy Planet
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Keywords asthma; cord blood; DNA-methylation; prenatal exposure
Abstract

Background

Childhood asthma is a result of a complex interaction of genetic and environmental components causing epigenetic and immune dysregulation, airway inflammation and impaired lung function. Although different microarray based EWAS studies have been conducted, the impact of epigenetic regulation in asthma development is still widely unknown. We have therefore applied unbiased whole genome bisulfite sequencing (WGBS) to characterize global DNA-methylation profiles of asthmatic children compared to healthy controls.

Methods

Peripheral blood samples of 40 asthmatic and 42 control children aged 5-15 years from three birth cohorts were sequenced together with paired cord blood samples. Identified differentially methylated regions (DMRs) were categorized in genotype-associated, cell-type-dependent, or prenatally-primed. Network analysis and subsequent natural language processing of DMR-associated genes was complemented by targeted analysis of functional translation of epigenetic regulation on the transcriptional and protein level.

Results

In total, 158 DMRs were identified in asthmatic children compared to controls of which 37% were related to the eosinophil content. A global hypomethylation was identified affecting predominantly enhancer regions and regulating key immune genes such as IL4, IL5RA, and EPX. These DMRs were confirmed in n=267 samples and could be linked to aberrant gene expression. Out of the 158 DMRs identified in the established phenotype, 56 were perturbed already at birth and linked, at least in part, to prenatal influences such as tobacco smoke exposure or phthalate exposure.

Conclusion

This is the first epigenetic study based on whole genome sequencing to identify marked dysregulation of enhancer regions as a hallmark of childhood asthma.

Persistent UFZ Identifier https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=25073
Thürmann, L., Klös, M., Mackowiak, S.D., Bieg, M., Bauer, T., Ishaque, N., Messingschlager, M., Herrmann, C., Röder, S., Bauer, M., Schäuble, S., Faessler, E., Hahn, U., Weichenhan, D., Mücke, O., Plass, C., Borte, M., von Mutius, E., Stangl, G.I., Lauener, R., Karvonen, A.M., Divaret-Chauveau, A., Riedler, J., Heinrich, J., Standl, M., von Berg, A., Schaaf, B., Herberth, G., Kabesch, M., Eils, R., Trump, S., Lehmann, I. (2023):
Global hypomethylation in childhood asthma identified by genome-wide DNA-methylation sequencing preferentially affects enhancer regions
Allergy 78 (6), 1489 - 1506