Association between long-term air pollution exposure and DNA methylation: The REGICOR study.
- Sayols-Baixeras S Cardiovascular Epidemiology and Genetics Research Group, IMIM (Hospital del Mar Medical Research Institute), Dr Aiguader 88, 08003 Barcelona, Catalonia, Spain; Universitat Pompeu Fabra (UPF), Dr Aiguader 88, 08003 Barcelona, Catalonia, Spain; CIBER Cardiovascular Diseases (CIBERCV), Dr Aiguader 88, 08003 Barcelona, Catalonia, Spain.
- Fernández-Sanlés A Cardiovascular Epidemiology and Genetics Research Group, IMIM (Hospital del Mar Medical Research Institute), Dr Aiguader 88, 08003 Barcelona, Catalonia, Spain; Universitat Pompeu Fabra (UPF), Dr Aiguader 88, 08003 Barcelona, Catalonia, Spain.
- Prats-Uribe A Cardiovascular Epidemiology and Genetics Research Group, IMIM (Hospital del Mar Medical Research Institute), Dr Aiguader 88, 08003 Barcelona, Catalonia, Spain; Preventive Medicine and Public Health Training Unit, Parc de Salut Mar-Universitat Pompeu Fabra-Agència de Salut Pública de Barcelona (UDMPiSP PSMar-UPF-ASPB), Dr Aiguader 88, 08003 Barcelona, Catalonia, Spain.
- Subirana I CIBER Epidemiology and Public Health (CIBERESP), Dr Aiguader 88, 08003 Barcelona, Catalonia, Spain; Cardiovascular Epidemiology and Genetics Research Group, IMIM (Hospital del Mar Medical Research Institute), Dr Aiguader 88, 08003 Barcelona, Catalonia, Spain.
- Plusquin M Department of Epidemiology and Biostatics, The School of Public Health, Imperial College London, Medical School Building, St Mary's Hospital, Norfolk Place, London, W2 1PG, United Kingdom; Medical Research Council-Health Protection Agency Centre for Environment and Health, Imperial College London, St Mary's Campus, Imperial College, Paddington, London, W2 1PG, United Kingdom; Centre for Environmental Sciences, Hasselt University, Campus Hasselt, Martelarenlaan 42, BE3500, Hasselt, Belgium.
- Künzli N Swiss Tropical and Public Health Institute, Socinstrasse 57, 4051, Basel, Switzerland; University of Basel, Klingelbergstrasse 61, 4056, Basel, Switzerland.
- Marrugat J REGICOR Research Group, IMIM (Hospital del Mar Medical Research Institute), DR Aiguader 88, 08003 Barcelona, Catalonia, Spain; CIBER Cardiovascular Diseases (CIBERCV), Dr Aiguader 88, 08003 Barcelona, Catalonia, Spain.
- Basagaña X ISGlobal (Institute for Global Health), Dr Aiguader 88, 08003 Barcelona, Spain; Universitat Pompeu Fabra (UPF), Dr Aiguader 88, 08003 Barcelona, Catalonia, Spain; CIBER Epidemiology and Public Health (CIBERESP), Dr Aiguader 88, 08003 Barcelona, Catalonia, Spain.
- Elosua R Cardiovascular Epidemiology and Genetics Research Group, IMIM (Hospital del Mar Medical Research Institute), Dr Aiguader 88, 08003 Barcelona, Catalonia, Spain; CIBER Cardiovascular Diseases (CIBERCV), Dr Aiguader 88, 08003 Barcelona, Catalonia, Spain; Faculty of Medicine, University of Vic-Central University of Catalonia (UVic-UCC), Carretera de Roda 70, 08500 Vic, Catalonia, Spain. Electronic address: relosua@imim.es.
- 2019-07-02
Published in:
- Environmental research. - 2019
Air pollution
DNA methylation
Epigenome-wide association study
Air Pollutants
Air Pollution
DNA Methylation
Environmental Exposure
Epigenesis, Genetic
Humans
Italy
English
INTRODUCTION
Limited evidence suggests that epigenetic mechanisms may partially mediate the adverse effects of air pollution on health. Our aims were to identify new genomic loci showing differential DNA methylation associated with long-term exposure to air pollution and to replicate loci previously identified in other studies.
METHODS
A two-stage epigenome-wide association study was designed: 630 individuals from the REGICOR study were included in the discovery and 454 participants of the EPIC-Italy study in the validation stage. DNA methylation was assessed using the Infinium HumanMethylation450 BeadChip. NOX, NO2, PM10, PM2.5, PMcoarse, traffic intensity and traffic load exposure were measured according to the ESCAPE protocol. A systematic review was undertaken to identify those cytosine-phosphate-guanine (CpGs) associated with air pollution in previous studies and we screened for them in the discovery study.
RESULTS
In the discovery stage of the epigenome-wide association study, 81 unique CpGs were associated with air pollution (p-value <10-5) but none of them were validated in the replication sample. Furthermore, we identified 15 CpGs in the systematic review showing differential methylation with a p-value fulfilling the Bonferroni criteria and 1673 CpGs fulfilling the false discovery rate criteria, all of which were related to PM2.5 or NO2. None of them was replicated in the discovery study, in which the top hits were located in an intergenic region on chromosome 1 (cg10893043, p-value = 6.79·10-5) and in the LRRC45 and PXK genes (cg05088605, p-value = 2.15·10-04; cg16560256, p-value = 2.23·10-04).
CONCLUSIONS
Neither new genomic loci associated with long-term air pollution were identified, nor previously identified loci were replicated. Continued efforts to test this potential association are warranted.
Limited evidence suggests that epigenetic mechanisms may partially mediate the adverse effects of air pollution on health. Our aims were to identify new genomic loci showing differential DNA methylation associated with long-term exposure to air pollution and to replicate loci previously identified in other studies.
METHODS
A two-stage epigenome-wide association study was designed: 630 individuals from the REGICOR study were included in the discovery and 454 participants of the EPIC-Italy study in the validation stage. DNA methylation was assessed using the Infinium HumanMethylation450 BeadChip. NOX, NO2, PM10, PM2.5, PMcoarse, traffic intensity and traffic load exposure were measured according to the ESCAPE protocol. A systematic review was undertaken to identify those cytosine-phosphate-guanine (CpGs) associated with air pollution in previous studies and we screened for them in the discovery study.
RESULTS
In the discovery stage of the epigenome-wide association study, 81 unique CpGs were associated with air pollution (p-value <10-5) but none of them were validated in the replication sample. Furthermore, we identified 15 CpGs in the systematic review showing differential methylation with a p-value fulfilling the Bonferroni criteria and 1673 CpGs fulfilling the false discovery rate criteria, all of which were related to PM2.5 or NO2. None of them was replicated in the discovery study, in which the top hits were located in an intergenic region on chromosome 1 (cg10893043, p-value = 6.79·10-5) and in the LRRC45 and PXK genes (cg05088605, p-value = 2.15·10-04; cg16560256, p-value = 2.23·10-04).
CONCLUSIONS
Neither new genomic loci associated with long-term air pollution were identified, nor previously identified loci were replicated. Continued efforts to test this potential association are warranted.
- Language
-
- English
- Open access status
- green
- Identifiers
-
- DOI 10.1016/j.envres.2019.108550
- PMID 31260916
- Persistent URL
- https://sonar.ch/global/documents/246888
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