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000212549 1001_ $$aThürmann, Loreen$$b0
000212549 245__ $$aGlobal hypomethylation in childhood asthma identified by genome-wide DNA-methylation sequencing preferentially affects enhancer regions.
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000212549 500__ $$a2023 Jun;78(6):1489-1506
000212549 520__ $$aChildhood asthma is a result of a complex interaction of genetic and environmental components causing epigenetic and immune dysregulation, airway inflammation and impaired lung function. Although different microarray based EWAS studies have been conducted, the impact of epigenetic regulation in asthma development is still widely unknown. We have therefore applied unbiased whole genome bisulfite sequencing (WGBS) to characterize global DNA-methylation profiles of asthmatic children compared to healthy controls.Peripheral blood samples of 40 asthmatic and 42 control children aged 5-15 years from three birth cohorts were sequenced together with paired cord blood samples. Identified differentially methylated regions (DMRs) were categorized in genotype-associated, cell-type-dependent, or prenatally-primed. Network analysis and subsequent natural language processing of DMR-associated genes was complemented by targeted analysis of functional translation of epigenetic regulation on the transcriptional and protein level.In total, 158 DMRs were identified in asthmatic children compared to controls of which 37% were related to the eosinophil content. A global hypomethylation was identified affecting predominantly enhancer regions and regulating key immune genes such as IL4, IL5RA, and EPX. These DMRs were confirmed in n=267 samples and could be linked to aberrant gene expression. Out of the 158 DMRs identified in the established phenotype, 56 were perturbed already at birth and linked, at least in part, to prenatal influences such as tobacco smoke exposure or phthalate exposure.This is the first epigenetic study based on whole genome sequencing to identify marked dysregulation of enhancer regions as a hallmark of childhood asthma.
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000212549 650_7 $$2Other$$aDNA-methylation
000212549 650_7 $$2Other$$aasthma
000212549 650_7 $$2Other$$acord blood
000212549 650_7 $$2Other$$aprenatal exposure
000212549 7001_ $$aKlös, Matthias$$b1
000212549 7001_ $$00000-0003-1673-5389$$aMackowiak, Sebastian D$$b2
000212549 7001_ $$aBieg, Matthias$$b3
000212549 7001_ $$0P:(DE-He78)ba69542e8644b99720d1446ad757efa8$$aBauer, Tobias$$b4
000212549 7001_ $$aIshaque, Naveed$$b5
000212549 7001_ $$00000-0002-7316-8192$$aMessingschlager, Marey$$b6
000212549 7001_ $$aHerrmann, Carl$$b7
000212549 7001_ $$aRöder, Stefan$$b8
000212549 7001_ $$00000-0001-5752-038X$$aBauer, Mario$$b9
000212549 7001_ $$aSchäuble, Sascha$$b10
000212549 7001_ $$aFaessler, Erik$$b11
000212549 7001_ $$aHahn, Udo$$b12
000212549 7001_ $$0P:(DE-He78)ff4024f7bc236e7897d9c18ee19c451f$$aWeichenhan, Dieter$$b13$$udkfz
000212549 7001_ $$0P:(DE-He78)aaef108f2a1ba0a78fff60ac60d3368c$$aMücke, Oliver$$b14$$udkfz
000212549 7001_ $$0P:(DE-He78)4301875630bc997edf491c694ae1f8a9$$aPlass, Christoph$$b15$$udkfz
000212549 7001_ $$aBorte, Michael$$b16
000212549 7001_ $$avon Mutius, Erika$$b17
000212549 7001_ $$aStangl, Gabriele I$$b18
000212549 7001_ $$aLauener, Roger$$b19
000212549 7001_ $$aKarvonen, Anne M$$b20
000212549 7001_ $$00000-0002-2492-9864$$aDivaret-Chauveau, Amandine$$b21
000212549 7001_ $$aRiedler, Josef$$b22
000212549 7001_ $$00000-0002-9620-1629$$aHeinrich, Joachim$$b23
000212549 7001_ $$00000-0002-5345-2049$$aStandl, Marie$$b24
000212549 7001_ $$avon Berg, Andrea$$b25
000212549 7001_ $$aSchaaf, Beate$$b26
000212549 7001_ $$aHerberth, Gunda$$b27
000212549 7001_ $$aKabesch, Michael$$b28
000212549 7001_ $$aEils, Roland$$b29
000212549 7001_ $$aTrump, Saskia$$b30
000212549 7001_ $$aLehmann, Irina$$b31
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