Integration of gene expression and DNA methylation identifies epigenetically controlled modules related to PM2.5 exposure
Author: Merid, Simon Kebede; Bustamante, Mariona; Standl, Marie; Sunyer, Jordi; Heinrich, Joachim; Lemonnier, Nathanaël; Aguilar, Daniel; Antó, Josep Maria; Bousquet, Jean; Santa-Marina, Loreto; Lertxundi, Aitana; Bergström, Anna; Kull, Inger; Wheelock, Åsa M; Koppelman, Gerard H; Melén, Erik; Gruzieva, Olena
Department: Inst för klinisk forskning och utbildning, Södersjukhuset / Dept of Clinical Science and Education, Södersjukhuset
View/ Open:
Author Accepted Manuscript (886.4Kb)
Abstract
Air pollution has been associated with adverse health effects across the life-course. Although underlying mechanisms are unclear, several studies suggested pollutant-induced changes in transcriptomic profiles. In this meta-analysis of transcriptome-wide association studies of 656 children and adolescents from three European cohorts participating in the MeDALL Consortium, we found two differentially expressed transcript clusters (FDR p < 0.05) associated with exposure to particulate matter < 2.5 µm in diameter (PM2.5) at birth, one of them mapping to the MIR1296 gene. Further, by integrating gene expression with DNA methylation using Functional Epigenetic Modules algorithms, we identified 9 and 6 modules in relation to PM2.5 exposure at birth and at current address, respectively (including NR1I2, MAPK6, TAF8 and SCARA3). In conclusion, PM2.5 exposure at birth was linked to differential gene expression in children and adolescents. Importantly, we identified several significant interactome hotspots of gene modules of relevance for complex diseases in relation to PM2.5 exposure.
Institution:
- Department of Clinical Sciences and Education, Karolinska Institutet, Södersjukhuset, Stockholm, Sweden
- Institute for Global Health, Barcelona, Spain
- Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain
- Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
- IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain
- Institute and Clinic for Occupational, Social and Environmental Medicine, University Hospital, LMU Munich, Munich, Germany
- Allergy and Lung Health Unit, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia
- Institute for Advanced Biosciences, UGA/INSERM U1209/CNRS UMR5309 joint research center, Allée des Alpes, France
- Biomedical Research Networking Center in Hepatic and Digestive Diseases (CIBEREHD), Instituto de Salud Carlos III, Barcelona, Spain
- Charité, Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, Berlin, Germany
- University Hospital, Montpellier, France MACVIA-France, Montpellier, France
- Health Research Institute-BIODONOSTIA, Basque Country, Spain
- CIBER Epidemiología y Salud Pública (CIBERESP), Spain
- Health Department of Basque Government, Sub-directorate of Public Health of Gipuzkoa, San Sebastian, Spain
- Preventive Medicine and Public Health Department, University of Basque Country (UPV/EHU), Spain
- Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
- Centre for Occupational and Environmental Medicine, Stockholm County Council, Sweden
- Sachs Children’s Hospital, Södersjukhuset, Stockholm, Sweden
- Respiratory Medicine Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden
- Department of Pediatric Pulmonology and Pediatric Allergology, Beatrix Children’s Hospital, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
- Groningen Research Institute for Asthma and COPD (GRIAC), University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
- Universitat Pompeu Fabra (UPF), Barcelona, Spain
- Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden
- Department of Dermatology and Allergy, Comprehensive Allergy Center, Berlin Institute of Health, Berlin, Germany
Citation: Environ Int. 2021 Jan;146:106248.
Citation DOI: 10.1016/j.envint.2020.106248
Citation PMID: 33212358
Citation ISI: 000604626300013
Publishing journal: Environment International
Eprint status: Peer Reviewed
Version: Accepted
Issue date: 2021-02-09
Sponsorship:
- EU’s Seventh Framework Program, ESCAPE 211250, MeDALL 76 261357
- European Research Council, TRIBAL 757919
- Swedish Research Council
- Swedish Heart-Lung Foundation
- Strategic Research Programme in Epidemiology at Karolinska Institutet
- Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning (Formas)
- Swedish Environment Protection Agency
- Swedish Asthma and Allergy Research Foundation
- Cancer and Allergy Foundation
- Swedish Research Council for Health, Working life and Welfare (Forte), 2017-01146
- Federal Ministry for Education, Science, Research and Technology
- Helmholtz Zentrum Munich
- Research Institute at Marien-Hospital Wesel, Munich
- Leibniz Research-Institute for Environmental Medicine
- Federal Ministry for Environment, IUF Düsseldorf, FKZ 20462296
- Mead Johnson
- Nestlé
- Instituto de Salud Carlos III, INMA G03/176, CB06/02/0041, PI04/1436, PI06/0867, PI08/1151, PI18/01142
- Generalitat de Catalunya-CIRIT, 1999SGR 00241
- Department of Health of the Basque Government, 2005111093
- Provincial Government of Gipuzkoa, DFG06/002
- Stockholm County Council
Rights:
CC BY 4.0
Publication year: 2020
Statistics
Total Visits
Views | |
---|---|
Integration ... | 365 |
Total Visits Per Month
March 2024 | April 2024 | May 2024 | June 2024 | July 2024 | August 2024 | September 2024 | |
---|---|---|---|---|---|---|---|
Integration ... | 3 | 3 | 4 | 3 | 3 | 11 | 5 |
File Visits
Views | |
---|---|
Manuscript_Merid_et_al.pdf | 250 |
AAM_Integration of gene expression and DNA methylation.pdf | 53 |
Manuscript_Merid_SK_EnvInt.pdf | 3 |
Top country views
Views | |
---|---|
United States | 94 |
Sweden | 89 |
Canada | 49 |
Germany | 26 |
South Korea | 17 |
France | 14 |
Ireland | 13 |
Russia | 9 |
India | 5 |
Vietnam | 5 |
Top cities views
Views | |
---|---|
Montreal | 46 |
Ashburn | 35 |
Bagarmossen | 12 |
Dublin | 12 |
Umeå | 7 |
Norrköping | 6 |
San Jose | 6 |
Bromma | 5 |
Ludwigshafen am Rhein | 5 |
Moscow | 5 |