Thuermann, Loreen and Kloes, Matthias and Mackowiak, Sebastian D. and Bieg, Matthias and Bauer, Tobias and Ishaque, Naveed and Messingschlager, Marey and Herrmann, Carl and Roeder, Stefan and Bauer, Mario and Schaeuble, Sascha and Faessler, Erik and Hahn, Udo and Weichenhan, Dieter and Muecke, Oliver and Plass, Christoph and Borte, Michael and von Mutius, Erika and Stangl, Gabriele I. and Lauener, Roger and Karvonen, Anne M. and Divaret-Chauveau, Amandine and Riedler, Josef and Heinrich, Joachim and Standl, Marie and von Berg, Andrea and Schaaf, Beate and Herberth, Gunda and Kabesch, Michael and Eils, Roland and Trump, Saskia and Lehmann, Irina (2023) Global hypomethylation in childhood asthma identified by genome-wide DNA-methylation sequencing preferentially affects enhancer regions. ALLERGY, 78 (6). pp. 1489-1506. ISSN 0105-4538, 1398-9995
Full text not available from this repository. (Request a copy)Abstract
BackgroundChildhood 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. MethodsPeripheral 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. ResultsIn 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. ConclusionThis is the first epigenetic study based on whole genome sequencing to identify marked dysregulation of enhancer regions as a hallmark of childhood asthma.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | IMMUNE; ENVIRONMENT; EXPRESSION; SYSTEM; BLOOD; RISK; asthma; cord blood; DNA-methylation; prenatal exposure |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Kinder- und Jugendmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 19 Apr 2024 13:23 |
| Last Modified: | 19 Apr 2024 13:23 |
| URI: | https://pred.uni-regensburg.de/id/eprint/60906 |
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