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Epigenome-wide meta-analysis of DNA methylation and childhood asthma.
Reese, Sarah E; Xu, Cheng-Jian; den Dekker, Herman T; Lee, Mi Kyeong; Sikdar, Sinjini; Ruiz-Arenas, Carlos; Merid, Simon K; Rezwan, Faisal I; Page, Christian M; Ullemar, Vilhelmina; Melton, Phillip E; Oh, Sam S; Yang, Ivana V; Burrows, Kimberley; Söderhäll, Cilla; Jima, Dereje D; Gao, Lu; Arathimos, Ryan; Küpers, Leanne K; Wielscher, Matthias; Rzehak, Peter; Lahti, Jari; Laprise, Catherine; Madore, Anne-Marie; Ward, James; Bennett, Brian D; Wang, Tianyuan; Bell, Douglas A; Vonk, Judith M; Håberg, Siri E; Zhao, Shanshan; Karlsson, Robert; Hollams, Elysia; Hu, Donglei; Richards, Adam J; Bergström, Anna; Sharp, Gemma C; Felix, Janine F; Bustamante, Mariona; Gruzieva, Olena; Maguire, Rachel L; Gilliland, Frank; Baïz, Nour; Nohr, Ellen A; Corpeleijn, Eva; Sebert, Sylvain; Karmaus, Wilfried; Grote, Veit; Kajantie, Eero; Magnus, Maria C.
Affiliation
  • Reese SE; Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC.
  • Xu CJ; Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Department of Pediatric Pulmonology and Pediatric Allergology, Beatrix Children's Hospital, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; GRIA
  • den Dekker HT; Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands; Department of Pediatrics, Division of Respiratory Medicine and Allergology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands; Generation R Study Group, Erasmus MC, Univ
  • Lee MK; Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC.
  • Sikdar S; Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC.
  • Ruiz-Arenas C; CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; ISGlobal, Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain.
  • Merid SK; Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
  • Rezwan FI; Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
  • Page CM; Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway; Oslo Centre for Biostatistics and Epidemiology, Oslo University Hospital, Oslo, Norway.
  • Ullemar V; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
  • Melton PE; Curtin/UWA Centre for Genetic Origins of Health and Disease, Faculty of Health and Medical Sciences, University of Western Australia, Crawley, Australia; School of Pharmacy and Biomedical Sciences, Curtin University, Bentley, Australia.
  • Oh SS; Department of Medicine, University of California San Francisco, San Francisco, Calif.
  • Yang IV; Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colo.
  • Burrows K; Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom; Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom.
  • Söderhäll C; Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden; Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
  • Jima DD; Bioinformatics Research Center, North Carolina State University, Raleigh, NC; Center for Human Health and the Environment, North Carolina State University, Raleigh, NC.
  • Gao L; Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, Calif.
  • Arathimos R; Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom; School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.
  • Küpers LK; Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom; Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom; Department of Epidemiology, University of Groningen, University Medical Center Gro
  • Wielscher M; Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment & Health, School of Public Health, Imperial College London, London, United Kingdom.
  • Rzehak P; Division of Metabolic and Nutritional Medicine, Dr. von Hauner Children's Hospital, Ludwig-Maximilians Universität München (LMU), Munich, Germany.
  • Lahti J; Department of Psychology and Logopedics, University of Helsinki, Helsinki, Finland; Helsinki Collegium for Advanced Studies, University of Helsinki, Helsinki, Finland.
  • Laprise C; Centre intégré universitaire de santé et de services sociaux du Saguenay, Saguenay, Quebec, Canada; Département des sciences fondamentales, Université du Québec à Chicoutimi, Saguenay, Quebec, Canada.
  • Madore AM; Département des sciences fondamentales, Université du Québec à Chicoutimi, Saguenay, Quebec, Canada.
  • Ward J; Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC.
  • Bennett BD; Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC.
  • Wang T; Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC.
  • Bell DA; Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC.
  • Vonk JM; GRIAC Research Institute, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
  • Håberg SE; Division of Mental and Physical Health, Norwegian Institute of Public Health, Oslo, Norway.
  • Zhao S; Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC.
  • Karlsson R; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
  • Hollams E; Telethon Kids Institute, University of Western Australia, Perth, Australia.
  • Hu D; Department of Medicine, University of California San Francisco, San Francisco, Calif.
  • Richards AJ; Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colo.
  • Bergström A; Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Centre for Occupational and Environmental Medicine, Stockholm County Council, Stockholm, Sweden.
  • Sharp GC; Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom; Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom; Bristol Dental School, University of Bristol, Bristol, United Kingdom.
  • Felix JF; Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands; Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands; Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Ne
  • Bustamante M; CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; ISGlobal, Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain; Center for Genomic Regulation (CRG), Barcelona Institute of Science and Technology, Barcelona, Spain.
  • Gruzieva O; Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Centre for Occupational and Environmental Medicine, Stockholm County Council, Stockholm, Sweden.
  • Maguire RL; Department of Biological Sciences, North Carolina State University, Raleigh, NC; Department of Community and Family Medicine, Duke University Medical Center, Durham, NC.
  • Gilliland F; Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, Calif.
  • Baïz N; Epidemiology of Allergic and Respiratory Diseases Department, IPLESP, INSERM and UPMC Sorbonne Université, Paris, France.
  • Nohr EA; Research Unit for Gynaecology and Obstetrics, Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
  • Corpeleijn E; Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
  • Sebert S; Biocenter Oulu, University of Oulu, Oulu, Finland; Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland; Department of Genomics of Complex Diseases, School of Public Health, Imperial College London, London, United Kingdom.
  • Karmaus W; Division of Epidemiology, Biostatistics and Environmental Health, School of Public Health, University of Memphis, Memphis, Tenn.
  • Grote V; Division of Metabolic and Nutritional Medicine, Dr. von Hauner Children's Hospital, Ludwig-Maximilians Universität München (LMU), Munich, Germany.
  • Kajantie E; Chronic Disease Prevention Unit, National Institute for Health and Welfare, Helsinki, Finland; Department of Obstetrics and Gynaecology, MRC Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland; Hospital for Children and Adolescents, Helsinki University Central Hospital and Universit
  • Magnus MC; Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom; Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom; Division of Mental and Physical Health, Norwegian Institute of Public Health, Oslo
J Allergy Clin Immunol ; 143(6): 2062-2074, 2019 06.
Article in En | MEDLINE | ID: mdl-30579849
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Asthma / CpG Islands / Interleukin-5 Receptor alpha Subunit / ERG1 Potassium Channel / Epigenome Type of study: Observational_studies / Prevalence_studies / Risk_factors_studies / Systematic_reviews Limits: Child / Humans / Newborn Language: En Journal: J Allergy Clin Immunol Year: 2019 Document type: Article Country of publication: United States
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Asthma / CpG Islands / Interleukin-5 Receptor alpha Subunit / ERG1 Potassium Channel / Epigenome Type of study: Observational_studies / Prevalence_studies / Risk_factors_studies / Systematic_reviews Limits: Child / Humans / Newborn Language: En Journal: J Allergy Clin Immunol Year: 2019 Document type: Article Country of publication: United States