Impact of long-term exposure to PM2.5 on peripheral blood gene expression pathways involved in cell signaling and immune response
Background: Exposure to ambient air pollution, even at low levels, is a major environmental health risk. The peripheral blood transcriptome provides a potential avenue for the elucidation of ambient air pollution related biological perturbations. We assessed the association between long-term estimat...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-10-01
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| Series: | Environment International |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0160412022004184 |
| _version_ | 1798003308814663680 |
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| author | Jelle Vlaanderen Roel Vermeulen Matthew Whitaker Marc Chadeau-Hyam Jouke-Jan Hottenga Eco de Geus Gonneke Willemsen Brenda W.J.H. Penninx Rick Jansen Dorret I. Boomsma |
| author_facet | Jelle Vlaanderen Roel Vermeulen Matthew Whitaker Marc Chadeau-Hyam Jouke-Jan Hottenga Eco de Geus Gonneke Willemsen Brenda W.J.H. Penninx Rick Jansen Dorret I. Boomsma |
| author_sort | Jelle Vlaanderen |
| collection | DOAJ |
| description | Background: Exposure to ambient air pollution, even at low levels, is a major environmental health risk. The peripheral blood transcriptome provides a potential avenue for the elucidation of ambient air pollution related biological perturbations. We assessed the association between long-term estimates for seven priority air pollutants and perturbations in peripheral blood transcriptomics data collected in the Dutch National Twin Register (NTR) and Netherlands Study of Depression and Anxiety (NESDA) cohorts. Methods: In both the discovery (n = 2438) and replication (n = 1567) cohort, outdoor concentration of 7 air pollutants (NO2, NOx, particulate matter (PM2.5, PM2.5abs, PM10, PMcoarse), and ultrafine particles) was predicted with land use regression models. Gene expression was assessed by Affymetrix U219 arrays. Multi-variable univariate mixed-effect models were applied to test for an association between the air pollutants and the transcriptome. Functional analysis was conducted in DAVID. Results: In the discovery cohort, we observed for 335 genes (374 probes with FDR < 5 %) a perturbation in peripheral blood gene expression that was associated with long-term average levels of PM2.5. For 69 genes pooled effect estimates from the NTR and NESDA cohorts were significant. Identified genes play a role in biological pathways related to cell signaling and immune response. Sixty-two out of 69 genes had a similar direction of effect in an analysis in which we regressed the probes on differential PM2.5 exposure within monozygotic twin pairs, indicating that the observed differences in gene expression were likely driven by differences in air pollution, rather than by confounding by genetic factors. Conclusion: Our results indicate that PM2.5 can elicit a response in cell signaling and the immune system, both hallmarks of environmental diseases. The differential effect that we observed between air pollutants may aid in the understanding of differential health effects that have been observed with these exposures. |
| first_indexed | 2024-04-11T12:05:41Z |
| format | Article |
| id | doaj.art-c35ffca3ca504e0cbb81992e73084682 |
| institution | Directory Open Access Journal |
| issn | 0160-4120 |
| language | English |
| last_indexed | 2024-04-11T12:05:41Z |
| publishDate | 2022-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Environment International |
| spelling | doaj.art-c35ffca3ca504e0cbb81992e730846822022-12-22T04:24:44ZengElsevierEnvironment International0160-41202022-10-01168107491Impact of long-term exposure to PM2.5 on peripheral blood gene expression pathways involved in cell signaling and immune responseJelle Vlaanderen0Roel Vermeulen1Matthew Whitaker2Marc Chadeau-Hyam3Jouke-Jan Hottenga4Eco de Geus5Gonneke Willemsen6Brenda W.J.H. Penninx7Rick Jansen8Dorret I. Boomsma9Institute for Risk Assessment Sciences, Utrecht University, the Netherlands; Corresponding author at: Division of Environmental Epidemiology, Institute for Risk Assessment Sciences (IRAS), Utrecht University, PO Box 80178, 3508 TD Utrecht, the Netherlands.Institute for Risk Assessment Sciences, Utrecht University, the Netherlands; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the NetherlandsSchool of Public Health, Imperial College London, London, UKSchool of Public Health, Imperial College London, London, UKDepartment of Biological Psychology, Vrije Universiteit, Amsterdam, the NetherlandsDepartment of Biological Psychology, Vrije Universiteit, Amsterdam, the NetherlandsDepartment of Biological Psychology, Vrije Universiteit, Amsterdam, the NetherlandsDepartment of Psychiatry, Amsterdam UMC Location Vrije Universiteit Amsterdam, Amsterdam Public Health Research Institute and Amsterdam Neuroscience, Amsterdam, the NetherlandsDepartment of Psychiatry, Amsterdam UMC Location Vrije Universiteit Amsterdam, Amsterdam Public Health Research Institute and Amsterdam Neuroscience, Amsterdam, the NetherlandsDepartment of Biological Psychology, Vrije Universiteit, Amsterdam, the NetherlandsBackground: Exposure to ambient air pollution, even at low levels, is a major environmental health risk. The peripheral blood transcriptome provides a potential avenue for the elucidation of ambient air pollution related biological perturbations. We assessed the association between long-term estimates for seven priority air pollutants and perturbations in peripheral blood transcriptomics data collected in the Dutch National Twin Register (NTR) and Netherlands Study of Depression and Anxiety (NESDA) cohorts. Methods: In both the discovery (n = 2438) and replication (n = 1567) cohort, outdoor concentration of 7 air pollutants (NO2, NOx, particulate matter (PM2.5, PM2.5abs, PM10, PMcoarse), and ultrafine particles) was predicted with land use regression models. Gene expression was assessed by Affymetrix U219 arrays. Multi-variable univariate mixed-effect models were applied to test for an association between the air pollutants and the transcriptome. Functional analysis was conducted in DAVID. Results: In the discovery cohort, we observed for 335 genes (374 probes with FDR < 5 %) a perturbation in peripheral blood gene expression that was associated with long-term average levels of PM2.5. For 69 genes pooled effect estimates from the NTR and NESDA cohorts were significant. Identified genes play a role in biological pathways related to cell signaling and immune response. Sixty-two out of 69 genes had a similar direction of effect in an analysis in which we regressed the probes on differential PM2.5 exposure within monozygotic twin pairs, indicating that the observed differences in gene expression were likely driven by differences in air pollution, rather than by confounding by genetic factors. Conclusion: Our results indicate that PM2.5 can elicit a response in cell signaling and the immune system, both hallmarks of environmental diseases. The differential effect that we observed between air pollutants may aid in the understanding of differential health effects that have been observed with these exposures.http://www.sciencedirect.com/science/article/pii/S0160412022004184Air pollutionTranscriptomicsMolecular epidemiologyBiological pathwaysCell signalingImmune system |
| spellingShingle | Jelle Vlaanderen Roel Vermeulen Matthew Whitaker Marc Chadeau-Hyam Jouke-Jan Hottenga Eco de Geus Gonneke Willemsen Brenda W.J.H. Penninx Rick Jansen Dorret I. Boomsma Impact of long-term exposure to PM2.5 on peripheral blood gene expression pathways involved in cell signaling and immune response Environment International Air pollution Transcriptomics Molecular epidemiology Biological pathways Cell signaling Immune system |
| title | Impact of long-term exposure to PM2.5 on peripheral blood gene expression pathways involved in cell signaling and immune response |
| title_full | Impact of long-term exposure to PM2.5 on peripheral blood gene expression pathways involved in cell signaling and immune response |
| title_fullStr | Impact of long-term exposure to PM2.5 on peripheral blood gene expression pathways involved in cell signaling and immune response |
| title_full_unstemmed | Impact of long-term exposure to PM2.5 on peripheral blood gene expression pathways involved in cell signaling and immune response |
| title_short | Impact of long-term exposure to PM2.5 on peripheral blood gene expression pathways involved in cell signaling and immune response |
| title_sort | impact of long term exposure to pm2 5 on peripheral blood gene expression pathways involved in cell signaling and immune response |
| topic | Air pollution Transcriptomics Molecular epidemiology Biological pathways Cell signaling Immune system |
| url | http://www.sciencedirect.com/science/article/pii/S0160412022004184 |
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