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Reese, S.E.* ; Xu, C.J.* ; den Dekker, H.T.* ; Lee, M.K.* ; Sikdar, S.* ; Ruiz-Arenas, C.* ; Merid, S.K.* ; Rezwan, F.I.* ; Page, C.M.* ; Ullemar, V.* ; Melton, P.E.* ; Oh, S.S.* ; Yang, I.V.* ; Burrows, K.* ; Söderhäll, C.* ; Jima, D.D.* ; Gao, L.* ; Arathimos, R.* ; Küpers, L.K.* ; Wielscher, M.* ; Rzehak, P.* ; Lahti, J.* ; Laprise, C.* ; Madore, A.M.* ; Ward, J.* ; Bennett, B.D.* ; Wang, T.* ; Bell, D.A.* ; Vonk, J.M.* ; Håberg, S.E.* ; Zhao, S.* ; Karlsson, R.* ; Hollams, E.* ; Hu, D.* ; Richards, A.J.* ; Bergström, A.* ; Sharp, G.C.* ; Felix, J.F.* ; Bustamante, M.* ; Gruzieva, O.* ; Maguire, R.L.* ; Gilliland, F.* ; Baïz, N.* ; Nohr, E.A.* ; Corpeleijn, E.* ; Sebert, S.* ; Karmaus, W.* ; Grote, V.* ; Kajantie, E.* ; Magnus, M.C.* ; Örtqvist, A.K.* ; Eng, C.* ; Liu, A.H.* ; Kull, I.* ; Jaddoe, V.W.V.* ; Sunyer, J.* ; Kere, J.* ; Hoyo, C.* ; Annesi-Maesano, I.* ; Arshad, S.H.* ; Koletzko, B.* ; Brunekreef, B.* ; Binder, E.B.* ; Räikkönen, K.* ; Reischl, E. ; Holloway, J.W.* ; Jarvelin, M.R.* ; Snieder, H.* ; Kazmi, N.* ; Breton, C.V.* ; Murphy, S.K.* ; Pershagen, G.* ; Antò, J.M.* ; Relton, C.L.* ; Schwartz, D.A.* ; Burchard, E.G.* ; Huang, R.C.* ; Nystad, W.* ; Almqvist, C.* ; Henderson, A.J.* ; Melén, E.* ; Duijts, L.* ; Koppelman, G.H.* ; London, S.J.*

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

J. Allergy Clin. Immunol. 143, 2062-2074 (2019)
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Background: 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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Epigenetics ; Methylation ; Asthma ; Childhood ; Newborn ; Drug Development; Prenatal Arsenic Exposure; Gene-expression; Cohort Profile; Cord Blood; Association; Epigenetics; Pregnancy; Risk; Consortium; Discovery
Language
Publication Year 2019
Prepublished in Year 2018
HGF-reported in Year 2018
ISSN (print) / ISBN 0091-6749
e-ISSN 1097-6825
Journal The journal of allergy and clinical immunology
Quellenangaben Volume: 143, Issue: 6, Pages: 2062-2074 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place Amsterdam [u.a.]
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology (EPI)
POF-Topic(s) 30202 - Environmental Health
Research field(s) Genetics and Epidemiology
PSP Element(s) G-504091-001
DOI 10.1016/j.jaci.2018.11.043
WOS ID WOS:000470113200012
Scopus ID 85060282097
PubMed ID 30579849
Erfassungsdatum 2019-01-10
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