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: University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, HUS Medical Imaging Center
University of Helsinki, HUS Abdominal Center
University of Helsinki, University Management
Date: 2019-07-01
Language: eng
Number of pages: 18
Belongs to series: European Respiratory Journal
ISSN: 0903-1936
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.
3121 Internal medicine

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