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

Authors :: Florian Kronenberg
Nicole Probst-Hensch
Diana A van der Plaat
Su Chen
Gertraud Erhart
A. J. Henderson
Anna Beckmeyer-Borowko
John M. Starr
Shadia Khan Sunny
Gemma C Sharp
H. Marike Boezen
John W. Holloway
Sarah E. Harris
Matthias Wielscher
Ian J. Deary
Åsa Johansson
Ayoung Jeong
Ian P. Hall
Yu Fu
Kim de Jong
Holger Schulz
Emmanuel Schaffner
Melanie Waldenberger
Ulf Gyllensten
Deborah Jarvis
Kirsi H. Pietiläinen
Päivi Piirilä
Marjo-Riitta Järvelin
Faisal I. Rezwan
Annette Peters
Maaike de Vries
Andre F.S. Amaral
Wilfried Karmaus
Miina Ollikainen
Yu Jiang
Claudia Flexeder
Medea Imboden
Martin D. Tobin
Ryan Arathimos
Groningen Research Institute for Asthma and COPD (GRIAC)
Life Course Epidemiology (LCE)
Commission of the European Communities
Institute for Molecular Medicine Finland
University of Helsinki
HUS Medical Imaging Center
Department of Diagnostics and Therapeutics
University Management
Clinicum
HUS Abdominal Center
Department of Medicine
Research Programs Unit
Diabetes and Obesity Research Program
Endokrinologian yksikkö
Epigenetics of Complex Diseases and Traits
Source :: Eur Respir J, European Respiratory Journal, 54(1):1900457. EUROPEAN RESPIRATORY SOC JOURNALS LTD, Imboden, M, Wielscher, M, Rezwan, F I, Amaral, A F S, Schaffner, E, Jeong, A, Beckmeyer-Borowko, A, Harris, S E, Starr, J M, Deary, I J, Flexeder, C, Waldenberger, M, Peters, A, Schulz, H, Chen, S, Sunny, S K, Karmaus, W J J, Jiang, Y, Erhart, G, Kronenberg, F, Arathimos, R, Sharp, G C, Fu, Y, Piirilä, P, Pietiläinen, K H, Ollikainen, M, Johansson, A, Gyllensten, U, de Vries, M, van der Plaat, D A, de Jong, K, Boezen, H M, Hall, I P, Tobin, M D, Jarvelin, M-R, Holloway, J W, Jarvis, D & Probst-Hensch, N M 2019, ' Epigenome-wide association study of lung function level and its change ', European Respiratory Journal, vol. 54, no. 1, 1900457 . https://doi.org/10.1183/13993003.00457-2019, Imboden, M, Wielscher, M, Rezwan, F I, Amaral, A F S, Schaffner, E, Jeong, A, Beckmeyer-Borowko, A, Harris, S, Starr, J, Deary, I, Flexeder, C, Waldenberger, M, Peters, A, Schulz, H, Chen, S, Shadia Khan, S, Karmaus, W J J, Jiang, Y, Erhart, G, Kronenberg, F, Arathimos, R, Sharp, G C, Henderson, A J, Fu, Y, Piirilä, P, Pietiläinen, K H, Ollikainen, M, Johansson, A, Gyllensten, U, de Vries, M, van der Plaat, D A, de Jong, K, Boezen, H M, Hall, I P, Tobin, M D, Jarvelin, M-R, Holloway, J W, Jarvis, D L & Probst-Hensch, N M 2019, ' Epigenome-wide association study of lung function level and its change ', European Respiratory Journal, vol. 53, no. 5 . https://doi.org/10.1183/13993003.00457-2019, Eur. Respir. J. 54, 1-18:1900457 (2019)
Publication Year :: 2018
Abstract: 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−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.