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

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BIOS Consortium , Reese , S E , Xu , C-J , den Dekker , H T , Lahti , J , Kajantie , E , Kere , J & Räikkönen , K 2019 , ' Epigenome-wide meta-analysis of DNA methylation and childhood asthma ' , Journal of Allergy and Clinical Immunology , vol. 143 , no. 6 , pp. 2062-2074 . https://doi.org/10.1016/j.jaci.2018.11.043

Title: Epigenome-wide meta-analysis of DNA methylation and childhood asthma
Author: BIOS Consortium; Reese, Sarah E.; Xu, Cheng-Jian; den Dekker, Herman T.; Lahti, Jari; Kajantie, Eero; Kere, Juha; Räikkönen, Katri
Contributor organization: Department of Psychology and Logopedics
Helsinki Collegium for Advanced Studies
Lastentautien yksikkö
Children's Hospital
University of Helsinki
HUS Children and Adolescents
Juha Kere / Principal Investigator
Developmental Psychology Research Group
Date: 2019-06
Language: eng
Number of pages: 13
Belongs to series: Journal of Allergy and Clinical Immunology
ISSN: 0091-6749
DOI: https://doi.org/10.1016/j.jaci.2018.11.043
URI: http://hdl.handle.net/10138/304057
Abstract: 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.
Subject: Epigenetics
drug development
3121 General medicine, internal medicine and other clinical medicine
3123 Gynaecology and paediatrics
Peer reviewed: Yes
Rights: cc_by_nc_nd
Usage restriction: openAccess
Self-archived version: acceptedVersion

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