Epigenome-wide meta-analysis of DNA methylation and childhood asthma

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  • dc.contributor.author Reese, Sarah E.
  • dc.contributor.author Ruiz Arenas, Carlos, 1990-
  • dc.contributor.author Antó i Boqué, Josep Maria
  • dc.contributor.author London, Stephanie J.
  • dc.date.accessioned 2019-07-22T07:57:20Z
  • dc.date.available 2019-07-22T07:57:20Z
  • dc.date.issued 2019
  • dc.description.abstract Epigenetic mechanisms, including methylation, can contribute to childhood asthma. Identifying DNA methylation profiles in asthmatic patients can inform disease pathogenesis. OBJECTIVE: We sought to identify differential DNA methylation in newborns and children related to childhood asthma. METHODS: Within the Pregnancy And Childhood Epigenetics consortium, we performed epigenome-wide meta-analyses of school-age asthma in relation to CpG methylation (Illumina450K) in blood measured either in newborns, in prospective analyses, or cross-sectionally in school-aged children. We also identified differentially methylated regions. RESULTS:In newborns (8 cohorts, 668 cases), 9 CpGs (and 35 regions) were differentially methylated (epigenome-wide significance, false discovery rate < 0.05) in relation to asthma development. In a cross-sectional meta-analysis of asthma and methylation in children (9 cohorts, 631 cases), we identified 179 CpGs (false discovery rate < 0.05) and 36 differentially methylated regions. In replication studies of methylation in other tissues, most of the 179 CpGs discovered in blood replicated, despite smaller sample sizes, in studies of nasal respiratory epithelium or eosinophils. Pathway analyses highlighted enrichment for asthma-relevant immune processes and overlap in pathways enriched both in newborns and children. Gene expression correlated with methylation at most loci. Functional annotation supports a regulatory effect on gene expression at many asthma-associated CpGs. Several implicated genes are targets for approved or experimental drugs, including IL5RA and KCNH2. CONCLUSION:Novel loci differentially methylated in newborns represent potential biomarkers of risk of asthma by school age. Cross-sectional associations in children can reflect both risk for and effects of disease. Asthma-related differential methylation in blood in children was substantially replicated in eosinophils and respiratory epithelium.
  • dc.description.sponsorship C. Ruiz-Arenas receives grant support from Agència de Gestió d’Ajuts Universitaris i de Recerca. S. S. Oh, C. Eng, and E. G. Burchard receive grant support from the NIH and the Tobacco-Related Disease Research Program. I. V. Yang and C. V. Breton receive grant support from the National Institutes of Health (NIH). C. Soderhall receives grant support from several competitive grants from public and private sources and receives royalties from book chapters instudy material. R. Arathimos and G. C. Sharp receive support from the Medical Research Council. E. Kajantie receives grant support from the European Commission,Academy of Finland, Foundation for Pediatric Research, Sigrid Juselius Foundation, Signe and Ane Gyllenberg Foundation, and Juho Vainio Foundation. G. Pershagen receives grant support from the Swedish Research Council. C. L. Relton receives grantsupport from Wellcome Trust. C. Almqvist receives grant support from the SwedishResearch Council through the Swedish Initiative for Research on Microdata in the So-cial And Medical Sciences (SIMSAM) framework, Stockholm County Council (ALF-projects), Swedish Heart-Lung Foundation, and Swedish Asthma and Allergy Associ-ation’s Research Foundation. A. J. Henderson receives grant support from the MedicalResearch Council and Wellcome Trust. E. Mel en received grant support from the Eu-ropean Research Council during conduct of the study and lecture fees from Thermo Fisher Scientific and Meda outside the submitted work. G. H. Koppelman receivesgrant support from the Lung Foundation of the Netherlands, MEDALL EU FP7, the UBBO EMMIUS Foundation, TEVA The Netherlands, Vertex, Glaxo Smith Kline, and the TETRI Foundation. The rest of the authors declare that they have no relevant conflicts of interest.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Reese SE, Xu CJ, den Dekker HT, Lee MK, Sikdar S, Ruiz-Arenas C et al. Epigenome-wide meta-analysis of DNA methylation and childhood asthma. J Allergy Clin Immunol. 2019 Jun;143(6):2062-74. DOI: 10.1016/j.jaci.2018.11.043
  • dc.identifier.doi http://dx.doi.org/10.1016/j.jaci.2018.11.043
  • dc.identifier.issn 0091-6749
  • dc.identifier.uri http://hdl.handle.net/10230/42128
  • dc.language.iso eng
  • dc.publisher Elsevier
  • dc.relation.ispartof Journal of Allergy and Clinical Immunology. 2019 Jun;143(6):2062-74
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/261357
  • dc.rights Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma &Immunology. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.keyword Epigenetics
  • dc.subject.keyword Asthma
  • dc.subject.keyword Childhood
  • dc.subject.keyword Drug development
  • dc.subject.keyword Methylation
  • dc.subject.keyword Newborn
  • dc.title Epigenome-wide meta-analysis of DNA methylation and childhood asthma
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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