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Thürmann, L.* ; Klös, M.* ; Mackowiak, S.D.* ; Bieg, M.* ; Bauer, T.* ; Ishaque, N.* ; Messingschlager, M.* ; Herrmann, C.* ; Roder, 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.*

Global hypomethylation in childhood asthma identified by genome-wide DNA-methylation sequencing preferentially affects enhancer regions.

Allergy 78, 1489-1506 (2023)
Verlagsversion DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Dna-methylation ; Asthma ; Cord Blood ; Prenatal Exposure; Immune; Environment; Expression; System; Blood; Risk
Sprache englisch
Veröffentlichungsjahr 2023
HGF-Berichtsjahr 2023
ISSN (print) / ISBN 0105-4538
e-ISSN 1398-9995
Zeitschrift Allergy
Quellenangaben Band: 78, Heft: 6, Seiten: 1489-1506 Artikelnummer: , Supplement: ,
Verlag Wiley
Verlagsort 111 River St, Hoboken 07030-5774, Nj Usa
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Asthma and Allergy Prevention (IAP)
Institute of Epidemiology (EPI)
POF Topic(s) 30202 - Environmental Health
Forschungsfeld(er) Allergy
Genetics and Epidemiology
PSP-Element(e) G-503300-001
G-504000-008
Förderungen Helmholtz cross program activity on Personalized Medicine (iMed)
Helmholtz Centre for Environmental Research-UFZ, Leipzig
Fondation du Souffle
European Union
Berlin Institute of Health at Charite - Universitatsmedizin Berlin
DOI 10.1111/all.15658
WOS ID 000940944200001
Scopus ID 85147710111
PubMed ID 36704932
Erfassungsdatum 2023-02-01
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