DNA methylation in inflammatory pathways modifies the association between BMI and adult-onset non-atopic asthma

Jeong, Ayoung; Imboden, Medea; Ghantous, Akram; Novoloaca, Alexei; Carsin, Anne-Elie; Kogevinas, Manolis; Schindler, Christian; Lovison, Gianfranco; Herceg, Zdenko; Cuenin, Cyrille; Vermeulen, Roel; Jarvis, Deborah; Amaral, André F.S.; Kronenberg, Florian; Vineis, Paolo; Probst-Hensch, Nicole

DNA methylation in inflammatory pathways modifies the association between BMI and adult-onset non-atopic asthma

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dc.contributor.author Jeong, Ayoung
dc.contributor.author Imboden, Medea
dc.contributor.author Ghantous, Akram
dc.contributor.author Novoloaca, Alexei
dc.contributor.author Carsin, Anne-Elie
dc.contributor.author Kogevinas, Manolis
dc.contributor.author Schindler, Christian
dc.contributor.author Lovison, Gianfranco
dc.contributor.author Herceg, Zdenko
dc.contributor.author Cuenin, Cyrille
dc.contributor.author Vermeulen, Roel
dc.contributor.author Jarvis, Deborah
dc.contributor.author Amaral, André F.S.
dc.contributor.author Kronenberg, Florian
dc.contributor.author Vineis, Paolo
dc.contributor.author Probst-Hensch, Nicole
dc.date.accessioned 2020-06-17T06:47:49Z
dc.date.available 2020-06-17T06:47:49Z
dc.date.issued 2019
dc.description.abstract A high body mass (BMI) index has repeatedly been associated with non-atopic asthma, but the biological mechanism linking obesity to asthma is still poorly understood. We aimed to test the hypothesis that inflammation and/or innate immunity plays a role in the obesity-asthma link. DNA methylome was measured in blood samples of 61 non-atopic participants with asthma and 146 non-atopic participants without asthma (non-smokers for at least 10 years) taking part in the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA) study. Modification by DNA methylation of the association of BMI or BMI change over 10 years with adult-onset asthma was examined at each CpG site and differentially methylated region. Pathway enrichment tests were conducted for genes in a priori curated inflammatory pathways and the NLRP3-IL1B-IL17 axis. The latter was chosen on the basis of previous work in mice. Inflammatory pathways including glucocorticoid/PPAR signaling (p = 0.0023), MAPK signaling (p = 0.013), NF-κB signaling (p = 0.031), and PI3K/AKT signaling (p = 0.031) were enriched for the effect modification of BMI, while NLRP3-IL1B-IL17 axis was enriched for the effect modification of BMI change over 10 years (p = 0.046). DNA methylation measured in peripheral blood is consistent with inflammation as a link between BMI and adult-onset asthma and with the NLRP3-IL1B-IL17 axis as a link between BMI change over 10 years and adult-onset asthma in non-atopic participants.
dc.description.sponsorship This work was supported by the grant FP7 of the European Commission “Enhanced exposure 36 assessment and omic profiling for high priority environmental exposures in Europe” (EXPOsOMICS grant 308610 to PV). The SAPALDIA study is supported by the Swiss National Science Foundation [grants no 33CS30-148470/1&2, 33CSCO-134276/1, 33CSCO-108796, 324730_135673, 3247BO-104283, 3247BO-104288, 3247BO-104284, 3247-065896, 3100-059302, 3200-052720, 3200-042532, 4026-028099, PMPDP3_129021/1, PMPDP3_141671/1], the Federal Office for the Environment, the Federal Office of Public Health, the Federal Office of Roads and Transport, the canton’s government of Aargau, Basel-Stadt, Basel-Land, Geneva, Luzern, Ticino, Valais, and Zürich, the Swiss Lung League, the canton’s Lung League of Basel Stadt/Basel Landschaft, Geneva, Ticino, Valais, Graubünden and Zurich, Stiftung ehemals Bündner Heilstätten, SUVA, Freiwillige Akademische Gesellschaft, Klinik Barmelweid, Hirslanden Klinik Aarau, the European Commission [Grant 018996 GABRIEL to W. Cookson], and the Wellcome Trust [WT 084703MA to W. Cookson]. This work was conducted within the Ageing Lungs in European Cohorts (ALEC) project and has received funding from the European Union’s Horizon 2020 research and innovation programm [grant agreement No 633212].
dc.format.mimetype application/pdf
dc.identifier.citation Jeong A, Imboden M, Ghantous A, Novoloaca A, Carsin AE, Kogevinas M, Schindler C, Lovison G, Herceg Z, Cuenin C, Vermeulen R, Jarvis D, Amaral AFS, Kronenberg F, Vineis P, Probst-Hensch N. DNA methylation in inflammatory pathways modifies the association between BMI and adult-onset non-atopic asthma. Int J Environ Res Public Health. 2019; 16(4):600. DOI: 10.3390/ijerph16040600
dc.identifier.doi http://dx.doi.org/10.3390/ijerph16040600
dc.identifier.issn 1661-7827
dc.identifier.uri http://hdl.handle.net/10230/44998
dc.language.iso eng
dc.publisher MDPI
dc.relation.ispartof Int J Environ Res Public Health. 2019; 16(4):600
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/308610
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/633212
dc.rights © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.subject.keyword DNA methylation
dc.subject.keyword Adult-onset asthma
dc.subject.keyword Epigenetics
dc.subject.keyword Epigenome-wide association study
dc.subject.keyword Inflammation
dc.subject.keyword Innate immunity
dc.subject.keyword Non-atopic asthma
dc.subject.keyword Obesity
dc.title DNA methylation in inflammatory pathways modifies the association between BMI and adult-onset non-atopic asthma
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/publishedVersion

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