| Title: |
Epigenome-wide meta-analysis of DNA methylation and childhood asthma |
| Authors: |
Reese, SE; Xu, C-J; Den Dekker, HT; Lee, MK; Sikdar, S; Ruiz-Arenas, C; Merid, SK; Rezwan, F; Page, CM; Ullemar, V; Melton, PE; Oh, SS; Yang, I; Burrows, K; Soderhall, C; Jima, DD; Gao, L; Arathimos, R; Kupers, LK; Wielscher, M; Rzehak, P; Lahti, J; Laprise, C; Madore, A-M; Ward, J; Bennett, BD; Wang, T; Bell, DA; Vonk, JM; Haberg, SE; Zhao, S; Karlsson, R; Hollams, E; Hu, D; Richards, AJ; Bergstrom, A; Sharp, GC; Felix, JF; Bustamante, M; Gruzieva, O; Maguire, RL; Gilliland, F; Baiz, N; Nohr, EA; Corpeleijn, E; Sebert, S; Karmaus, W; Grote, V; Kajantie, E; Magnus, MC; Ortqvist, AK; Eng, C; Liu, AH; Kull, I; Jaddoe, VWV; Sunyer, J; Kere, J; Hoyo, C; Annesi-Maesano, I; Arshad, SH; Koletzko, B; Brunekreef, B; Binder, EB; Raikkonen, K; Reischl, E; Holloway, JW; Jarvelin, M-R; Snieder, H; Kazmi, N; Breton, C; Murphy, SK; Pershagen, G; Maria Anto, J; Relton, CL; Schwartz, DA; Burchard, EG; Huang, R-C; Nystad, W-C; Almqvist, C; Henderson, AJ; Melen, E; Duijts, L; Koppelman, GH; London, SJ |
| Contributors: |
UNIVERSITY OF OULU; Commission of the European Communities |
| Source: |
2074 ; 2062 |
| Publisher Information: |
Elsevier |
| Publication Year: |
2018 |
| Collection: |
Imperial College London: Spiral |
| Subject Terms: |
Science & Technology; Life Sciences & Biomedicine; Allergy; Immunology; Epigenetics; methylation; asthma; childhood; newborn; drug development; PRENATAL ARSENIC EXPOSURE; GENE-EXPRESSION; COHORT PROFILE; CORD BLOOD; ASSOCIATION; PREGNANCY; RISK; CONSORTIUM; DISCOVERY; Child; CpG Islands; Cross-Sectional Studies; DNA Methylation; ERG1 Potassium Channel; Epigenesis; Genetic; Epigenome; Genome-Wide Association Study; Humans; Infant |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
Journal of Allergy and Clinical Immunology; http://hdl.handle.net/10044/1/85470; Nil; 633212 |
| DOI: |
10.1016/j.jaci.2018.11.043 |
| Availability: |
http://hdl.handle.net/10044/1/85470; https://doi.org/10.1016/j.jaci.2018.11.043 |
| Rights: |
© 2018 The Author(s). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) ; http://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.5676C39E |
| Database: |
BASE |