10.5061/DRYAD.PR10C20
Imboden, Medea
Swiss Tropical and Public Health Institute
Wielscher, Matthias
Public Health England
Rezwan, Faisal I
University of Southampton
Amaral, Andre F S
Public Health England
Schaffner, Emmanuel
Swiss Tropical and Public Health Institute
Jeong, Ayoung
Swiss Tropical and Public Health Institute
Beckmeyer-Borowko, Anna
Swiss Tropical and Public Health Institute
Harris, Sarah E
University of Edinburgh
Starr, John M
University of Edinburgh
Deary, Ian J
University of Edinburgh
Flexeder, Claudia
Helmholtz Zentrum München
Waldenberger, Melanie
Helmholtz Zentrum München
Peters, Annette
Helmholtz Zentrum München
Schulz, Holger
Helmholtz Zentrum München
Chen, Su
University of Memphis
Sunny, Shadia KHan
University of Memphis
Karmaus, Wilfried J J
University of Memphis
Jiang, Yu
University of Memphis
Erhart, Gertraud
University of Innsbruck
Kronenberg, Florian
University of Innsbruck
Arathimos, Ryan
University of Bristol
Sharp, Gemma C
University of Bristol
Henderson, Alexander John
University of Bristol
Fu, Yu
Institute for Molecular Medicine Finland
Piirila, Paivi
University of Helsinki
Pietilainen, Kirsi H
University of Helsinki
Ollikainen, Miina
Institute for Molecular Medicine Finland
Johannson, Asa
Science for Life Laboratory
Gyllensten, Ulf
Science for Life Laboratory
de Vries, Maaike
University Medical Center Groningen
van der Plaat, Diana
University Medical Center Groningen
de Jong, Kim
University Medical Center Groningen
Boezen, Hendrika M
Hall, Ian P
University of Nottingham
Tobin, Martin D
University of Leicester
Järvelin, Marjo-Riitta
Holloway, John W
University of Southampton
Jarvis, Deborah
Public Health England
Probst-Hensch, Nicole M
Swiss Tropical and Public Health Institute
Data from: Epigenome-wide association study of lung function level and its
change
Dryad
dataset
2019
genome-wide
lung function
Smoking
Homo Sapiens
Epigenetics
2019-06-06T13:19:58Z
2019-06-06T13:19:58Z
en
https://doi.org/10.1183/13993003.00457-2019
5809317427 bytes
1
CC0 1.0 Universal (CC0 1.0) Public Domain Dedication
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<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.
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.
EUROPE
Europe