In:
European Respiratory Journal, European Respiratory Society (ERS), Vol. 54, No. 1 ( 2019-07), p. 1900457-
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 〈 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 (FEV 1 ), forced vital capacity (FVC) and their ratio (FEV 1 /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 (FEV 1 /FVC: p discovery =3.96×10 −21 and p combined =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 (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.
Type of Medium:
Online Resource
ISSN:
0903-1936
,
1399-3003
DOI:
10.1183/13993003.00457-2019
DOI:
10.1183/13993003.00457-2019.Supp1
Language:
English
Publisher:
European Respiratory Society (ERS)
Publication Date:
2019
detail.hit.zdb_id:
2834928-3
detail.hit.zdb_id:
1499101-9
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