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

Imboden, Medea and Wielscher, Matthias and Rezwan, Faisal I. and Amaral, André F. S. and Schaffner, Emmanuel and Jeong, Ayoung and Beckmeyer-Borowko, Anna and Harris, Sarah E. and Starr, John M. and Deary, Ian J. and Flexeder, Claudia and Waldenberger, Melanie and Peters, Annette and Schulz, Holger and Chen, Su and Sunny, Shadia Khan and Karmaus, Wilfried J. J. and Jiang, Yu and Erhart, Gertraud and Kronenberg, Florian and Arathimos, Ryan and Sharp, Gemma C. and Henderson, Alexander John and Fu, Yu and Piirilä, Päivi and Pietiläinen, Kirsi H. and Ollikainen, Miina and Johansson, Asa and Gyllensten, Ulf and de Vries, Maaike and van der Plaat, Diana A. and de Jong, Kim and Boezen, H. Marike and Hall, Ian P. and Tobin, Martin D. and Jarvelin, Marjo-Riitta and Holloway, John W. and Jarvis, Deborah and Probst-Hensch, Nicole M.. (2019) Epigenome-wide association study of lung function level and its change. The European respiratory journal, 54. p. 1900457.

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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.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Epidemiology and Public Health (EPH) > Chronic Disease Epidemiology > Genetic Epidemiology of Non-Communicable Diseases (Probst-Hensch)
03 Faculty of Medicine > Departement Public Health > Sozial- und Präventivmedizin > Genetic Epidemiology of Non-Communicable Diseases (Probst-Hensch)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Epidemiology and Public Health (EPH) > Biostatistics > Biostatistics Frequentist Modelling
UniBasel Contributors:Imboden, Medea and Schaffner, Emmanuel and Jeong, Ayoung and Beckmeyer-Borowko, Anna and Probst Hensch, Nicole
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Munksgaard
ISSN:0903-1936
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
Last Modified:10 Jul 2019 13:52
Deposited On:10 Jul 2019 13:52

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