1. DNA methylation in childhood asthma
- Author
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Mariona Bustamante, Francesco Forastiere, Henriette A. Smit, Petter Mowinckel, Marjan Kerkhof, Tari Haahtela, Martijn C. Nawijn, Raul Aguirre-Gamboa, Dan Mason, Mihai G. Netea, Cisca Wijmenga, Raf Azad, Vegard Hovland, John Wright, Josep M. Antó, Cilla Söderhäll, Pieter van der Vlies, William O.C.M. Cookson, Bianca van Rijkom, Lovisa E. Reinius, Soesma A Jankipersadsing, Leda Chatzi, Nour Baïz, Erik Melén, Daniela Porta, Olena Gruzieva, Juha Kere, Isabella Annesi-Maesano, Maties Torrent, Charles Auffray, Cleo C. van Diemen, Manolis Kogevinas, Davide Gori, Johann Pellet, Jose Ramon Bilbao, Harri Alenius, Göran Pershagen, Sabrina Llop, Miriam F. Moffatt, Nathanaël Lemonnier, Ashok Kumar, Simon Kebede Merid, Nanna Fyhrquist, Stephane Ballereau, Tiina Laatikainen, Cheng-Jian Xu, Johan C. de Jongste, Marc Jan Bonder, Judith Garcia-Aymerich, Karin C. Lødrup Carlsen, J Sunyer, Mikel Basterrechea, Dario Greco, Yang Li, Jean Bousquet, Ulrike Gehring, Catherine Laprise, Maria Pia Fantini, Rosemary R. C. McEachan, Bert Brunekreef, Stefano Guerra, Gerard H. Koppelman, Cornelis J. Vermeulen, Andréanne Morin, Carmen Iñiguez, Kai-Håkon Carlsen, Center for Research in Environmental Epidemiology (CREAL), Universitat Pompeu Fabra [Barcelona] (UPF)-Catalunya ministerio de salud, CIBER de Epidemiología y Salud Pública (CIBERESP), IMIM-Hospital del Mar, Generalitat de Catalunya, Universitat Pompeu Fabra [Barcelona] (UPF), Karolinska Institutet [Stockholm], University of Helsinki, King‘s College London, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Stockholm County Council, Aging Research Center [Karolinska Institutet] (ARC ), Stockholm University-Karolinska Institutet [Stockholm], Keck School of Medicine [Los Angeles], University of Southern California (USC), Azienda Sanitaria Locale [ROMA] (ASL), McGill University and Genome Quebec Innovation Centre, Département des Sciences Fondamentales [Chicoutimi] (DSF), Université du Québec à Chicoutimi (UQAC), European Institute for Systems Biology and Medicine (EISBM), Arizona Respiratory Center, Radboud University Medical Center [Nijmegen], Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Department of Dermatology, Allergology and Venereology, Clinicum, Medicum, Department of Bacteriology and Immunology, HUS Inflammation Center, One Health Chemisch, dIRAS RA-2, Pediatrics, RS: NUTRIM - R3 - Respiratory & Age-related Health, Complexe Genetica, RS: NUTRIM - R4 - Gene-environment interaction, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Xu, Cheng-Jian, Söderhäll, Cilla, Bustamante, Mariona, Baïz, Nour, Gruzieva, Olena, Gehring, Ulrike, Mason, Dan, Chatzi, Leda, Basterrechea, Mikel, Llop, Sabrina, Torrent, Matie, Forastiere, Francesco, Fantini, Maria Pia, Carlsen, Karin C Lødrup, Haahtela, Tari, Morin, Andréanne, Kerkhof, Marjan, Merid, Simon Kebede, van Rijkom, Bianca, Jankipersadsing, Soesma A., Bonder, Marc Jan, Ballereau, Stephane, Vermeulen, Cornelis J., Aguirre-Gamboa, Raul, de Jongste, Johan C., Smit, Henriette A., Kumar, Ashish, Pershagen, Göran, Guerra, Stefano, Garcia-Aymerich, Judith, Greco, Dario, Reinius, Lovisa, McEachan, Rosemary R.C., Azad, Raf, Hovland, Vegard, Mowinckel, Petter, Alenius, Harri, Fyhrquist, Nanna, Lemonnier, Nathanaël, Pellet, Johann, Auffray, Charle, van der Vlies, Pieter, van Diemen, Cleo C., Li, Yang, Wijmenga, Cisca, Netea, Mihai G., Moffatt, Miriam F., Cookson, William O.C.M., Anto, Josep M., Bousquet, Jean, Laatikainen, Tiina, Laprise, Catherine, Carlsen, Kai-Håkon, Gori, Davide, Porta, Daniela, Iñiguez, Carmen, Bilbao, Jose Ramon, Kogevinas, Manoli, Wright, John, Brunekreef, Bert, Kere, Juha, Nawijn, Martijn C., Annesi-Maesano, Isabella, Sunyer, Jordi, Melén, Erik, and Koppelman, Gerard H.
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Male ,0301 basic medicine ,Allergy ,Cytotoxic ,T-Lymphocytes ,[SDV]Life Sciences [q-bio] ,Respiratory System ,lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] ,CHILDREN ,Immunoglobulin E ,Epigenesis, Genetic ,Child ,POPULATION ,education.field_of_study ,biology ,Methylation ,3. Good health ,CpG site ,Child, Preschool ,DNA methylation ,Female ,BIOS Consortium ,Life Sciences & Biomedicine ,Pulmonary and Respiratory Medicine ,Population ,PHENOTYPES ,IMMUNITY ,03 medical and health sciences ,Critical Care Medicine ,Genetic ,General & Internal Medicine ,medicine ,Humans ,COHORT ,Epigenetics ,IGE ,EXPOSURE ,Preschool ,education ,Asthma ,Science & Technology ,business.industry ,RHINITIS ,DNA ,DNA Methylation ,medicine.disease ,Eosinophils ,030104 developmental biology ,3121 General medicine, internal medicine and other clinical medicine ,Immunology ,biology.protein ,GENOMEWIDE ASSOCIATION ,CpG Islands ,business ,COLLECTION ,T-Lymphocytes, Cytotoxic ,Epigenesis ,Genome-Wide Association Study - Abstract
Background: DNA methylation profiles associated with childhood asthma might provide novel insights into disease pathogenesis. We did an epigenome-wide association study to assess methylation profiles associated with childhood asthma. Methods: We did a large-scale epigenome-wide association study (EWAS) within the Mechanisms of the Development of ALLergy (MeDALL) project. We examined epigenome-wide methylation using Illumina Infinium Human Methylation450 BeadChips (450K) in whole blood in 207 children with asthma and 610 controls at age 4–5 years, and 185 children with asthma and 546 controls at age 8 years using a cross-sectional case-control design. After identification of differentially methylated CpG sites in the discovery analysis, we did a validation study in children (4–16 years; 247 cases and 2949 controls) from six additional European cohorts and meta-analysed the results. We next investigated whether replicated CpG sites in cord blood predict later asthma in 1316 children. We subsequently investigated cell-type-specific methylation of the identified CpG sites in eosinophils and respiratory epithelial cells and their related gene-expression signatures. We studied cell-type specificity of the asthma association of the replicated CpG sites in 455 respiratory epithelial cell samples, collected by nasal brushing of 16-year-old children as well as in DNA isolated from blood eosinophils (16 with asthma, eight controls [age 2–56 years]) and compared this with whole-blood DNA samples of 74 individuals with asthma and 93 controls (age 1–79 years). Whole-blood transcriptional profiles associated with replicated CpG sites were annotated using RNA-seq data of subsets of peripheral blood mononuclear cells sorted by fluorescence-activated cell sorting. Findings: 27 methylated CpG sites were identified in the discovery analysis. 14 of these CpG sites were replicated and passed genome-wide significance (p
- Published
- 2018
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