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

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Reese, SE, Xu, C-J, den Dekker, HT, Lee, MK, Sikdar, S, Ruiz-Arenas, C, Merid, SK, Rezwan, FI, Page, CM, Ullemar, V, Melton, PE ORCID: 0000-0003-4026-2964, Oh, SS, Yang, IV, 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, CV, Murphy, SK, Pershagen, G, Anto, JM, Relton, CL, Schwartz, DA, Burchard, EG, Huang, R-C, Nystad, W, Almqvist, C, Henderson, AJ, Melen, E, Duijts, L, Koppelman, GH and London, SJ 2019 , 'Epigenome-wide meta-analysis of DNA methylation and childhood asthma' , Journal of Allergy and Clinical Immunology, vol. 143, no. 6 , pp. 2062-2074 , doi: 10.1016/j.jaci.2018.11.043.

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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 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.

Item Type: Article
Authors/Creators:Reese, SE and Xu, C-J and den Dekker, HT and Lee, MK and Sikdar, S and Ruiz-Arenas, C and Merid, SK and Rezwan, FI and Page, CM and Ullemar, V and Melton, PE and Oh, SS and Yang, IV and Burrows, K and Soderhall, C and Jima, DD and Gao, L and Arathimos, R and Kupers, LK and Wielscher, M and Rzehak, P and Lahti, J and Laprise, C and Madore, A-M and Ward, J and Bennett, BD and Wang, T and Bell, DA and Vonk, JM and Haberg, SE and Zhao, S and Karlsson, R and Hollams, E and Hu, D and Richards, AJ and Bergstrom, A and Sharp, GC and Felix, JF and Bustamante, M and Gruzieva, O and Maguire, RL and Gilliland, F and Baiz, N and Nohr, EA and Corpeleijn, E and Sebert, S and Karmaus, W and Grote, V and Kajantie, E and Magnus, MC and Ortqvist, AK and Eng, C and Liu, AH and Kull, I and Jaddoe, VWV and Sunyer, J and Kere, J and Hoyo, C and Annesi-Maesano, I and Arshad, SH and Koletzko, B and Brunekreef, B and Binder, EB and Raikkonen, K and Reischl, E and Holloway, JW and Jarvelin, M-R and Snieder, H and Kazmi, N and Breton, CV and Murphy, SK and Pershagen, G and Anto, JM and Relton, CL and Schwartz, DA and Burchard, EG and Huang, R-C and Nystad, W and Almqvist, C and Henderson, AJ and Melen, E and Duijts, L and Koppelman, GH and London, SJ
Keywords: epigenetics, asthma, childhood, drug development, methylation, newborn
Journal or Publication Title: Journal of Allergy and Clinical Immunology
Publisher: Mosby
ISSN: 0091-6749
DOI / ID Number: 10.1016/j.jaci.2018.11.043
Copyright Information:

Copyright © 2021 Elsevier B.V. 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://creative commons.org/licenses/by/4.0/).

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