DOI: 10.5061/dryad.pr10c20
title: Data from: Epigenome-wide association study of lung function level and its change

description: 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=2,043). Associated DNAme markers (P&lt;5x10-7) were tested
 in seven replication cohorts (adult: n=3,327; childhood: n=420).
 Technical-bias adjusted residuals of a regression of the normalized
 absolute beta-values on control-probe-derived principle components were
 regressed on level and change of FEV1, FEV1/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 (FEV1/FVC: Pdiscovery=3.96x10-21 and Pcombined=7.22x10-50).
 A score combining ten DNAme markers previously reported to mediate the
 smoking effect 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.
description: statistical_codescontains the statistical codes used to: 1- derive residuals of methylation data ; 2a - run EWAS cross-sectionally; 2b - run EWAS as repeated cross-sectional analysis; 2c - run EWAS predictive association with change in outcome; 3a - meta-analysis script for replication ; 3b - combined discovery and replication meta-analysis script.DiscoveryResultsByCohorts_archive.tarThis archive contains all the cohort-specific discovery EWAS results. See read-me file for details.DiscoveryResultsByCohorts.tar.gzDiscoveryMetaResults_archive.tarThis archive contains all the discovery EWAS meta-analysed results. See read-me file for details.DiscoveryMetaResults.tar.gzReplicationResultsByCohorts.tarThis archive contains all the cohort-specific replication results. See read-me file for details.ReplicationMetaResults.tarThis archive contains all the replication meta-analysed results. See read-me file for details.CombinedMetaResults.tarThis archive contains the discovery cohort and replication cohort combined meta-analysed results. See read-me file for details.ChildhoodMetaResults.tarThis archive contains all the childhood cohort replication meta-analysed results. See read-me file for details.