Epigenome-wide association study of lung function level and its change.

Autor:	Imboden M; Chronic Disease Epidemiology Unit, Dept of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland.; University of Basel, Basel, Switzerland.; These authors contributed equally to this work., Wielscher M; MRC-PHE Centre for Environment and Health, Imperial College London, London, UK.; Dept of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.; These authors contributed equally to this work., Rezwan FI; Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK.; These authors contributed equally to this work., Amaral AFS; MRC-PHE Centre for Environment and Health, Imperial College London, London, UK.; Population Health and Occupational Disease, NHLI, Imperial College London, London, UK.; These authors contributed equally to this work., Schaffner E; Chronic Disease Epidemiology Unit, Dept of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland.; University of Basel, Basel, Switzerland., Jeong A; Chronic Disease Epidemiology Unit, Dept of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland.; University of Basel, Basel, Switzerland., Beckmeyer-Borowko A; Chronic Disease Epidemiology Unit, Dept of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland.; University of Basel, Basel, Switzerland., Harris SE; Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.; Medical Genetics Section, University of Edinburgh Centre for Genomic and Experimental Medicine and MRC Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, UK., Starr JM; Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.; Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh, UK., Deary IJ; Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.; Dept of Psychology, University of Edinburgh, Edinburgh, UK., Flexeder C; Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany., Waldenberger M; Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.; Research Unit Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany., Peters A; Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.; Research Unit Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany., Schulz H; Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.; Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research (DZL), Munich, Germany., Chen S; Dept of Mathematical Sciences, University of Memphis, Memphis, TN, USA., Sunny SK; Division of Epidemiology, Biostatistics, and Environmental Health, School of Public Health, University of Memphis, Memphis, TN, USA., Karmaus WJJ; Division of Epidemiology, Biostatistics, and Environmental Health, School of Public Health, University of Memphis, Memphis, TN, USA., Jiang Y; Division of Epidemiology, Biostatistics, and Environmental Health, School of Public Health, University of Memphis, Memphis, TN, USA., Erhart G; Division of Genetic Epidemiology, Dept of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria., Kronenberg F; Division of Genetic Epidemiology, Dept of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria., Arathimos R; MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.; Dept of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK., Sharp GC; MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.; Dept of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.; Bristol Dental School, University of Bristol, Bristol, UK., Henderson AJ; Dept of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK., Fu Y; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland., Piirilä P; Unit of Clinical Physiology, HUS Medical Imaging Center, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland., Pietiläinen KH; Obesity Research Unit, Research Programs Unit, University of Helsinki, Helsinki, Finland.; Abdominal Center, Endocrinology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland., Ollikainen M; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland., Johansson A; Dept of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden., Gyllensten U; Dept of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden., de Vries M; University of Groningen, University Medical Center Groningen, Dept of Epidemiology, Groningen, The Netherlands.; Groningen Research Institute for Asthma and COPD (GRIAC), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., van der Plaat DA; University of Groningen, University Medical Center Groningen, Dept of Epidemiology, Groningen, The Netherlands.; Groningen Research Institute for Asthma and COPD (GRIAC), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., de Jong K; University of Groningen, University Medical Center Groningen, Dept of Epidemiology, Groningen, The Netherlands.; Groningen Research Institute for Asthma and COPD (GRIAC), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., Boezen HM; University of Groningen, University Medical Center Groningen, Dept of Epidemiology, Groningen, The Netherlands.; Groningen Research Institute for Asthma and COPD (GRIAC), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., Hall IP; Division of Respiratory Medicine, University of Nottingham, Nottingham, UK.; National Institute for Health Research, Nottingham Biomedical Research Centre, Nottingham University Hospitals, Nottingham, UK., Tobin MD; Dept of Health Sciences, University of Leicester, Leicester, UK.; National Institute of Health Research Biomedical Research Centre, University of Leicester, Leicester, UK., Jarvelin MR; Dept of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.; Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland.; Biocenter Oulu, University of Oulu, Oulu, Finland.; Unit of Primary Health Care, Oulu University Hospital, Oulu, Finland.; Dept of Life Sciences, College of Health and Life Sciences, Brunel University London, London, UK.; These authors contributed equally to this work., Holloway JW; Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK.; These authors contributed equally to this work., Jarvis D; MRC-PHE Centre for Environment and Health, Imperial College London, London, UK.; Population Health and Occupational Disease, NHLI, Imperial College London, London, UK.; These authors contributed equally to this work., Probst-Hensch NM; Chronic Disease Epidemiology Unit, Dept of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland.; University of Basel, Basel, Switzerland.; These authors contributed equally to this work.
Jazyk:	angličtina
Zdroj:	The European respiratory journal [Eur Respir J] 2019 Jul 04; Vol. 54 (1). Date of Electronic Publication: 2019 Jul 04 (Print Publication: 2019).
DOI:	10.1183/13993003.00457-2019
Abstrakt:	Previous reports link differential DNA methylation (DNAme) to environmental exposures that are associated with lung function. Direct evidence on lung function DNAme is, however, limited. We undertook an agnostic epigenome-wide association study (EWAS) on pre-bronchodilation lung function and its change in adults.In a discovery-replication EWAS design, DNAme in blood and spirometry were measured twice, 6-15 years apart, in the same participants of three adult population-based discovery cohorts (n=2043). Associated DNAme markers (p<5×10 -7 ) were tested in seven replication cohorts (adult: n=3327; childhood: n=420). Technical bias-adjusted residuals of a regression of the normalised absolute β-values on control probe-derived principle components were regressed on level and change of forced expiratory volume in 1 s (FEV 1 ), forced vital capacity (FVC) and their ratio (FEV 1 /FVC) in the covariate-adjusted discovery EWAS. Inverse-variance-weighted meta-analyses were performed on results from discovery and replication samples in all participants and never-smokers.EWAS signals were enriched for smoking-related DNAme. We replicated 57 lung function DNAme markers in adult, but not childhood samples, all previously associated with smoking. Markers not previously associated with smoking failed replication. cg05575921 ( AHRR (aryl hydrocarbon receptor repressor)) showed the statistically most significant association with cross-sectional lung function (FEV 1 /FVC: p discovery =3.96×10 -21 and p combined =7.22×10 -50 ). A score combining 10 DNAme markers previously reported to mediate the effect of smoking on lung function was associated with lung function (FEV 1 /FVC: p=2.65×10 -20 ).Our results reveal that lung function-associated methylation signals in adults are predominantly smoking related, and possibly of clinical utility in identifying poor lung function and accelerated decline. Larger studies with more repeat time-points are needed to identify lung function DNAme in never-smokers and in children. Competing Interests: Conflict of interest: M. Imboden has nothing to disclose. Conflict of interest: M. Wielscher has nothing to disclose. Conflict of interest: F.I. Rezwan has nothing to disclose. Conflict of interest: A.F.S. Amaral has nothing to disclose. Conflict of interest: E. Schaffner has nothing to disclose. Conflict of interest: A. Jeong has nothing to disclose. Conflict of interest: A. Beckmeyer-Borowko has nothing to disclose. Conflict of interest: S.E. Harris reports grants from Medical Research Council, Biotechnology and Biological Sciences Research Council, Age UK and The Wellcome Trust, during the conduct of the study. Conflict of interest: J.M. Starr has nothing to disclose. Conflict of interest: I.J. Deary reports grants from Age UK and Medical Research Council, during the conduct of the study. Conflict of interest: C. Flexeder has nothing to disclose. Conflict of interest: M. Waldenberger has nothing to disclose. Conflict of interest: A. Peters has nothing to disclose. Conflict of interest: H. Schulz reports grants from German Federal Ministry of Education and Research (BMBF), during the conduct of the study. Conflict of interest: S. Chen has nothing to disclose. Conflict of interest: S.K. Sunny has nothing to disclose. Conflict of interest: W.J.J. Karmaus has nothing to disclose. Conflict of interest: Y. Jiang has nothing to disclose. Conflict of interest: G. Erhart has nothing to disclose. Conflict of interest: F. Kronenberg has nothing to disclose. Conflict of interest: R. Arathimos has nothing to disclose. Conflict of interest: G.C. Sharp has nothing to disclose. Conflict of interest: A.J. Henderson reports grants from Medical Research Council and Wellcome Trust, during the conduct of the study. Conflict of interest: Y. Fu has nothing to disclose. Conflict of interest: P. Piirilä has nothing to disclose. Conflict of interest: K.H. Pietiläinen has nothing to disclose. Conflict of interest: M. Ollikainen has nothing to disclose. Conflict of interest: A. Johansson has nothing to disclose. Conflict of interest: U. Gyllensten has nothing to disclose. Conflict of interest: M de Vries has nothing to disclose. Conflict of interest: D.A. van der Plaat has nothing to disclose. Conflict of interest: K. de Jong has nothing to disclose. Conflict of interest: H.M. Boezen has nothing to disclose. Conflict of interest: I.P. Hall reports grants from GSK and Boehringer Ingelheim, outside the submitted work. Conflict of interest: M.D. Tobin reports grants from Pfizer and GSK, outside the submitted work. Conflict of interest: M-R. Jarvelin has nothing to disclose. Conflict of interest: J.W. Holloway reports grants from European Union and National Institutes of Health, during the conduct of the study. Conflict of interest: D. Jarvis reports grants from European Union, Medical Research Council and Asthma UK, during the conduct of the study. Conflict of interest: N.M. Probst-Hensch has nothing to disclose. (Copyright ©ERS 2019.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu