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

Data from: Epigenome-wide association study of lung function level and its change
Data from: Epigenome-wide association study of lung function level and its change
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.,
DRYAD
Imboden, Medea
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Schaffner, Emmanuel
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Fu, Yu
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Piirila, Paivi
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Pietilainen, Kirsi H
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Ollikainen, Miina
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Johannson, Asa
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Gyllensten, Ulf
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De Vries, Maaike
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De Jong, Kim
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Hall, Ian P
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Järvelin, Marjo-Riitta
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Probst-Hensch, Nicole M
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Imboden, Medea
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Wielscher, Matthias
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Amaral, Andre F S
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Schaffner, Emmanuel
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Jeong, Ayoung
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Beckmeyer-Borowko, Anna
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Harris, Sarah E
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Starr, John M
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Deary, Ian J
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Flexeder, Claudia
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Waldenberger, Melanie
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Chen, Su
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Sunny, Shadia KHan
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Karmaus, Wilfried J J
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Jiang, Yu
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Erhart, Gertraud
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Kronenberg, Florian
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Arathimos, Ryan
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Sharp, Gemma C
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Henderson, Alexander John
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Fu, Yu
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Piirila, Paivi
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Pietilainen, Kirsi H
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Ollikainen, Miina
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Johannson, Asa
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Gyllensten, Ulf
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De Vries, Maaike
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Van Der Plaat, Diana
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De Jong, Kim
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Boezen, Hendrika M
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Hall, Ian P
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Tobin, Martin D
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Järvelin, Marjo-Riitta
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Holloway, John W
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Jarvis, Deborah
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Probst-Hensch, Nicole M
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Imboden, Medea, Wielscher, Matthias, Amaral, Andre F S, Schaffner, Emmanuel, Jeong, Ayoung, Beckmeyer-Borowko, Anna, Starr, John M, Deary, Ian J, Flexeder, Claudia, Waldenberger, Melanie, Peters, Annette, Schulz, Holger, Sunny, Shadia KHan, Karmaus, Wilfried J J, Jiang, Yu, Erhart, Gertraud, Kronenberg, Florian, Arathimos, Ryan, Sharp, Gemma C, Henderson, Alexander John, Fu, Yu, Piirila, Paivi, Ollikainen, Miina, Gyllensten, Ulf, Van Der Plaat, Diana, De Jong, Kim, Hall, Ian P, Tobin, Martin D, Järvelin, Marjo-Riitta, Jarvis, Deborah and Probst-Hensch, Nicole M (2019) Data from: Epigenome-wide association study of lung function level and its change. DRYAD doi:10.5061/dryad.pr10c20 [Dataset]

Record type: Dataset

Abstract

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.,

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More information

Published date: 1 January 2019

Identifiers

Local EPrints ID: 449320
URI: http://eprints.soton.ac.uk/id/eprint/449320
PURE UUID: 1be7a152-5fbd-44c6-9cf5-d43b5a395170
ORCID for Faisal I Rezwan: ORCID iD orcid.org/0000-0001-9921-222X
ORCID for John W Holloway: ORCID iD orcid.org/0000-0001-9998-0464

Catalogue record

Date deposited: 24 May 2021 16:32
Last modified: 17 Jul 2021 01:48

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Contributors

Creator: Medea Imboden
Creator: Matthias Wielscher
Contributor: Faisal I Rezwan ORCID iD
Creator: Andre F S Amaral
Creator: Emmanuel Schaffner
Creator: Ayoung Jeong
Creator: Anna Beckmeyer-Borowko
Contributor: Sarah E Harris
Creator: John M Starr
Creator: Ian J Deary
Creator: Claudia Flexeder
Creator: Melanie Waldenberger
Creator: Annette Peters
Creator: Holger Schulz
Contributor: Su Chen
Creator: Shadia KHan Sunny
Creator: Wilfried J J Karmaus
Creator: Yu Jiang
Creator: Gertraud Erhart
Creator: Florian Kronenberg
Creator: Ryan Arathimos
Creator: Gemma C Sharp
Creator: Alexander John Henderson
Creator: Yu Fu
Creator: Paivi Piirila
Contributor: Kirsi H Pietilainen
Creator: Miina Ollikainen
Contributor: Asa Johannson
Creator: Ulf Gyllensten
Contributor: Maaike De Vries
Creator: Diana Van Der Plaat
Creator: Kim De Jong
Contributor: Hendrika M Boezen
Creator: Ian P Hall
Creator: Martin D Tobin
Creator: Marjo-Riitta Järvelin
Contributor: John W Holloway ORCID iD
Creator: Deborah Jarvis
Creator: Nicole M Probst-Hensch

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