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

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...

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Main Authors:	Reese, S., Xu, C., den Dekker, H., Lee, M., Sikdar, S., Ruiz-Arenas, C., Merid, S., Rezwan, F., Page, C., Ullemar, V., Melton, Phillip, Oh, S., Yang, I., Burrows, K., Söderhäll, C., Jima, D., Gao, L., Arathimos, R., Küpers, L., Wielscher, M., Rzehak, P., Lahti, J., Laprise, C., Madore, A., Ward, J., Bennett, B., Wang, T., Bell, D., Vonk, J., Håberg, S., Zhao, S., Karlsson, R., Hollams, E., Hu, D., Richards, A., Bergström, A., Sharp, G., Felix, J., Bustamante, M., Gruzieva, O., Maguire, R., Gilliland, F., Baïz, N., Nohr, E., Corpeleijn, E., Sebert, S., Karmaus, W., Grote, V., Kajantie, E., Magnus, M., Örtqvist, A., Eng, C., Liu, A., Kull, I., Jaddoe, V., Sunyer, J., Kere, J., Hoyo, C., Annesi-Maesano, I.
Format:	Journal Article
Published:	Mosby, Inc. 2019
Online Access:	http://hdl.handle.net/20.500.11937/74559

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author	Reese, S. Xu, C. den Dekker, H. Lee, M. Sikdar, S. Ruiz-Arenas, C. Merid, S. Rezwan, F. Page, C. Ullemar, V. Melton, Phillip Oh, S. Yang, I. Burrows, K. Söderhäll, C. Jima, D. Gao, L. Arathimos, R. Küpers, L. Wielscher, M. Rzehak, P. Lahti, J. Laprise, C. Madore, A. Ward, J. Bennett, B. Wang, T. Bell, D. Vonk, J. Håberg, S. Zhao, S. Karlsson, R. Hollams, E. Hu, D. Richards, A. Bergström, A. Sharp, G. Felix, J. Bustamante, M. Gruzieva, O. Maguire, R. Gilliland, F. Baïz, N. Nohr, E. Corpeleijn, E. Sebert, S. Karmaus, W. Grote, V. Kajantie, E. Magnus, M. Örtqvist, A. Eng, C. Liu, A. Kull, I. Jaddoe, V. Sunyer, J. Kere, J. Hoyo, C. Annesi-Maesano, I.
author_facet	Reese, S. Xu, C. den Dekker, H. Lee, M. Sikdar, S. Ruiz-Arenas, C. Merid, S. Rezwan, F. Page, C. Ullemar, V. Melton, Phillip Oh, S. Yang, I. Burrows, K. Söderhäll, C. Jima, D. Gao, L. Arathimos, R. Küpers, L. Wielscher, M. Rzehak, P. Lahti, J. Laprise, C. Madore, A. Ward, J. Bennett, B. Wang, T. Bell, D. Vonk, J. Håberg, S. Zhao, S. Karlsson, R. Hollams, E. Hu, D. Richards, A. Bergström, A. Sharp, G. Felix, J. Bustamante, M. Gruzieva, O. Maguire, R. Gilliland, F. Baïz, N. Nohr, E. Corpeleijn, E. Sebert, S. Karmaus, W. Grote, V. Kajantie, E. Magnus, M. Örtqvist, A. Eng, C. Liu, A. Kull, I. Jaddoe, V. Sunyer, J. Kere, J. Hoyo, C. Annesi-Maesano, I.
author_sort	Reese, S.
building	Curtin Institutional Repository
collection	Online Access
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.
first_indexed	2025-11-14T11:01:25Z
format	Journal Article
id	curtin-20.500.11937-74559
institution	Curtin University Malaysia
institution_category	Local University
last_indexed	2025-11-14T11:01:25Z
publishDate	2019
publisher	Mosby, Inc.
recordtype	eprints
repository_type	Digital Repository
spelling	curtin-20.500.11937-745592019-07-16T06:02:35Z Epigenome-wide meta-analysis of DNA methylation and childhood asthma Reese, S. Xu, C. den Dekker, H. Lee, M. Sikdar, S. Ruiz-Arenas, C. Merid, S. Rezwan, F. Page, C. Ullemar, V. Melton, Phillip Oh, S. Yang, I. Burrows, K. Söderhäll, C. Jima, D. Gao, L. Arathimos, R. Küpers, L. Wielscher, M. Rzehak, P. Lahti, J. Laprise, C. Madore, A. Ward, J. Bennett, B. Wang, T. Bell, D. Vonk, J. Håberg, S. Zhao, S. Karlsson, R. Hollams, E. Hu, D. Richards, A. Bergström, A. Sharp, G. Felix, J. Bustamante, M. Gruzieva, O. Maguire, R. Gilliland, F. Baïz, N. Nohr, E. Corpeleijn, E. Sebert, S. Karmaus, W. Grote, V. Kajantie, E. Magnus, M. Örtqvist, A. Eng, C. Liu, A. Kull, I. Jaddoe, V. Sunyer, J. Kere, J. Hoyo, C. Annesi-Maesano, I. 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. 2019 Journal Article http://hdl.handle.net/20.500.11937/74559 10.1016/j.jaci.2018.11.043 http://creativecommons.org/licenses/by/4.0/ Mosby, Inc. fulltext
spellingShingle	Reese, S. Xu, C. den Dekker, H. Lee, M. Sikdar, S. Ruiz-Arenas, C. Merid, S. Rezwan, F. Page, C. Ullemar, V. Melton, Phillip Oh, S. Yang, I. Burrows, K. Söderhäll, C. Jima, D. Gao, L. Arathimos, R. Küpers, L. Wielscher, M. Rzehak, P. Lahti, J. Laprise, C. Madore, A. Ward, J. Bennett, B. Wang, T. Bell, D. Vonk, J. Håberg, S. Zhao, S. Karlsson, R. Hollams, E. Hu, D. Richards, A. Bergström, A. Sharp, G. Felix, J. Bustamante, M. Gruzieva, O. Maguire, R. Gilliland, F. Baïz, N. Nohr, E. Corpeleijn, E. Sebert, S. Karmaus, W. Grote, V. Kajantie, E. Magnus, M. Örtqvist, A. Eng, C. Liu, A. Kull, I. Jaddoe, V. Sunyer, J. Kere, J. Hoyo, C. Annesi-Maesano, I. Epigenome-wide meta-analysis of DNA methylation and childhood asthma
title	Epigenome-wide meta-analysis of DNA methylation and childhood asthma
title_full	Epigenome-wide meta-analysis of DNA methylation and childhood asthma
title_fullStr	Epigenome-wide meta-analysis of DNA methylation and childhood asthma
title_full_unstemmed	Epigenome-wide meta-analysis of DNA methylation and childhood asthma
title_short	Epigenome-wide meta-analysis of DNA methylation and childhood asthma
title_sort	epigenome-wide meta-analysis of dna methylation and childhood asthma
url	http://hdl.handle.net/20.500.11937/74559

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

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