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

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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 , 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 & 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

Title: Epigenome-wide association study of lung function level and its change
Author: Imboden, Medea; Wielscher, Matthias; Rezwan, Faisal I.; Amaral, Andre 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.
Contributor organization: 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
Date: 2019-07-01
Language: eng
Number of pages: 18
Belongs to series: European Respiratory Journal
ISSN: 0903-1936
DOI: https://doi.org/10.1183/13993003.00457-2019
URI: http://hdl.handle.net/10138/306599
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 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=3.96x10(-21) and pcombined=7.22x10(-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=2.65x10(-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.
Subject: OBSTRUCTIVE PULMONARY-DISEASE
DNA METHYLATION
SMOKING
BLOOD
3121 General medicine, internal medicine and other clinical medicine
Peer reviewed: Yes
Usage restriction: openAccess
Self-archived version: publishedVersion


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