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@ARTICLE{Thrmann:212549,
      author       = {L. Thürmann and M. Klös and S. D. Mackowiak and M. Bieg
                      and T. Bauer$^*$ and N. Ishaque and M. Messingschlager and
                      C. Herrmann and S. Röder and M. Bauer and S. Schäuble and
                      E. Faessler and U. Hahn and D. Weichenhan$^*$ and O.
                      Mücke$^*$ and C. Plass$^*$ and M. Borte and E. von Mutius
                      and G. I. Stangl and R. Lauener and A. M. Karvonen and A.
                      Divaret-Chauveau and J. Riedler and J. Heinrich and M.
                      Standl and A. von Berg and B. Schaaf and G. Herberth and M.
                      Kabesch and R. Eils and S. Trump and I. Lehmann},
      title        = {{G}lobal hypomethylation in childhood asthma identified by
                      genome-wide {DNA}-methylation sequencing preferentially
                      affects enhancer regions.},
      journal      = {Allergy},
      volume       = {78},
      number       = {6},
      issn         = {0105-4538},
      address      = {Oxford},
      publisher    = {Wiley},
      reportid     = {DKFZ-2023-00234},
      pages        = {1489-1506},
      year         = {2023},
      note         = {2023 Jun;78(6):1489-1506},
      abstract     = {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.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.},
      keywords     = {DNA-methylation (Other) / asthma (Other) / cord blood
                      (Other) / prenatal exposure (Other)},
      cin          = {B080 / B370},
      ddc          = {610},
      cid          = {I:(DE-He78)B080-20160331 / I:(DE-He78)B370-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:36704932},
      doi          = {10.1111/all.15658},
      url          = {https://inrepo02.dkfz.de/record/212549},
}