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Epigenome-wide association study of lung function level and its change |
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| Author: | Imboden, Medea1,2; Wielscher, Matthias3,4; Rezwan, Faisal I.5; |
| Organizations: |
1Chronic Disease Epidemiology Unit, Dept of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland 2University of Basel, Basel, Switzerland 3MRC-PHE Centre for Environment and Health, Imperial College London, London, UK
4Dept of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
5Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK 6Population Health and Occupational Disease, NHLI, Imperial College London, London, UK 7Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK 8Medical Genetics Section, University of Edinburgh Centre for Genomic and Experimental Medicine and MRC Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, UK 9Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh, UK 10Dept of Psychology, University of Edinburgh, Edinburgh, UK 11Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany 12Research Unit Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany 13Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research (DZL), Munich, Germany 14Dept of Mathematical Sciences, University of Memphis, Memphis, TN, USA 15Division of Epidemiology, Biostatistics, and Environmental Health, School of Public Health, University of Memphis, Memphis, TN, USA 16Division of Genetic Epidemiology, Dept of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria 17MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK 18Dept of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK 19Bristol Dental School, University of Bristol, Bristol, UK 20Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland 21Unit of Clinical Physiology, HUS Medical Imaging Center, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland 22Obesity Research Unit, Research Programs Unit, University of Helsinki, Helsinki, Finland 23Abdominal Center, Endocrinology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland 24Dept of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden 25University of Groningen, University Medical Center Groningen, Dept of Epidemiology, Groningen, The Netherlands 26Groningen Research Institute for Asthma and COPD (GRIAC), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands 27Division of Respiratory Medicine, University of Nottingham, Nottingham, UK 28National Institute for Health Research, Nottingham Biomedical Research Centre, Nottingham University Hospitals, Nottingham, UK 29Dept of Health Sciences, University of Leicester, Leicester, UK 30National Institute of Health Research Biomedical Research Centre, University of Leicester, Leicester, UK 31Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland 32Biocenter Oulu, University of Oulu, Oulu, Finland 33Unit of Primary Health Care, Oulu University Hospital, Oulu, Finland 34Dept of Life Sciences, College of Health and Life Sciences, Brunel University London, London, UK |
| Format: | article |
| Version: | published version |
| Access: | open |
| Online Access: | PDF Full Text (PDF, 1 MB) |
| Persistent link: | http://urn.fi/urn:nbn:fi-fe202003269331 |
| Language: | English |
| Published: |
European Respiratory Society,
2019
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| Publish Date: | 2020-03-26 |
| Description: |
AbstractPrevious 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 (FEV1), forced vital capacity (FVC) and their ratio (FEV1/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 (FEV1/FVC: pdiscovery=3.96×10−21 and pcombined=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 (FEV1/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. see all
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| Series: |
European respiratory journal |
| ISSN: | 0903-1936 |
| ISSN-E: | 1399-3003 |
| ISSN-L: | 0903-1936 |
| Volume: | 54 |
| Issue: | 1 |
| Article number: | 1900457 |
| DOI: | 10.1183/13993003.00457-2019 |
| OADOI: | https://oadoi.org/10.1183/13993003.00457-2019 |
| Type of Publication: |
A1 Journal article – refereed |
| Field of Science: |
3121 General medicine, internal medicine and other clinical medicine |
| Subjects: | |
| Funding: |
This work has been conducted within the Aging Lungs in European Cohorts (ALEC) project, funded from the European Union’s Horizon 2020 research and innovation programme under grant agreement 633212. The funding agency had no role in the design, data collection and analysis of the data. Cohort-specific funding details are provided in the supplementary material. Funding information for this article has been deposited with the Crossref Funder Registry. |
| Copyright information: |
© ERS 2019. This version is distributed under the terms of the Creative Commons Attribution Licence 4.0. |
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https://creativecommons.org/licenses/by/4.0/ |