RT Journal Article
SR Electronic
T1 Epigenome-wide association study of lung function level and its change
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 1900457
DO 10.1183/13993003.00457-2019
VO 54
IS 1
A1 Medea Imboden
A1 Matthias Wielscher
A1 Faisal I. Rezwan
A1 André F.S. Amaral
A1 Emmanuel Schaffner
A1 Ayoung Jeong
A1 Anna Beckmeyer-Borowko
A1 Sarah E. Harris
A1 John M. Starr
A1 Ian J. Deary
A1 Claudia Flexeder
A1 Melanie Waldenberger
A1 Annette Peters
A1 Holger Schulz
A1 Su Chen
A1 Shadia Khan Sunny
A1 Wilfried J.J. Karmaus
A1 Yu Jiang
A1 Gertraud Erhart
A1 Florian Kronenberg
A1 Ryan Arathimos
A1 Gemma C. Sharp
A1 Alexander John Henderson
A1 Yu Fu
A1 Päivi Piirilä
A1 Kirsi H. Pietiläinen
A1 Miina Ollikainen
A1 Asa Johansson
A1 Ulf Gyllensten
A1 Maaike de Vries
A1 Diana A. van der Plaat
A1 Kim de Jong
A1 H. Marike Boezen
A1 Ian P. Hall
A1 Martin D. Tobin
A1 Marjo-Riitta Jarvelin
A1 John W. Holloway
A1 Deborah Jarvis
A1 Nicole M. Probst-Hensch
YR 2019
UL http://erj.ersjournals.com/content/54/1/1900457.abstract
AB 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 (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.An agnostic association study on lung function using longitudinal population-based cohort data shows that differentially methylated genomic sites related to smoking are strongly associated with lung function in adults http://ow.ly/wYID30onUB4