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Epigenome-wide association study of lung function level and its change
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
ID 4509214
Author(s) Imboden, Medea; Wielscher, Matthias; Rezwan, Faisal I.; Amaral, André F. S.; Schaffner, Emmanuel; Jeong, Ayoung; Beckmeyer-Borowko, Anna; Harris, Sarah E.; Starr, John M.; Deary, Ian J.; Flexeder, Claudia; Waldenberger, Melanie; Peters, Annette; Schulz, Holger; Chen, Su; Sunny, Shadia Khan; Karmaus, Wilfried J. J.; Jiang, Yu; Erhart, Gertraud; Kronenberg, Florian; Arathimos, Ryan; Sharp, Gemma C.; Henderson, Alexander John; Fu, Yu; Piirilä, Päivi; Pietiläinen, Kirsi H.; Ollikainen, Miina; Johansson, Asa; Gyllensten, Ulf; de Vries, Maaike; van der Plaat, Diana A.; de Jong, Kim; Boezen, H. Marike; Hall, Ian P.; Tobin, Martin D.; Jarvelin, Marjo-Riitta; Holloway, John W.; Jarvis, Deborah; Probst-Hensch, Nicole M.
Author(s) at UniBasel Imboden, Medea
Schaffner, Emmanuel
Jeong, Ayoung
Beckmeyer-Borowko, Anna
Probst Hensch, Nicole
Year 2019
Title Epigenome-wide association study of lung function level and its change
Journal The European respiratory journal
Volume 54
Number 1
Pages / Article-Number 1900457
Abstract Previous reports link differential DNA methylation (DNAme) to environmental exposures which 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, six-to-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 beta-values on control-probe-derived principle components were regressed on level and change of FEV; 1; , FEV; 1; /FVC and FVC in 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 in adult, but not childhood samples, all previously associated with smoking. Markers not previously associated with smoking failed replication. cg05575921 (; AHRR; ) 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 ten DNAme markers previously reported to mediate the smoking effect 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.
Publisher Munksgaard
ISSN/ISBN 0903-1936
Full Text on edoc Available
Digital Object Identifier DOI 10.1183/13993003.00457-2019
PubMed ID
ISI-Number MEDLINE:31073081
Document type (ISI) Journal Article

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