TY - JOUR
T1 - Occupational exposure to gases/fumes and mineral dust affect DNA methylation levels of genes regulating expression
AU - van Der Plaat, Diana
AU - Vonk, Judith M.
AU - Terzikhan, Natalie
AU - de Jong, Kim
AU - de Vries, Maaike
AU - La Bastide-van Gemert, Sacha
AU - van Diemen, Cleo C.
AU - Lahousse, Lies
AU - Brusselle, Guy
AU - Nedeljkovic, Ivana
AU - Amin, Najaf
AU - Kromhout, Hans
AU - Vermeulen, Roel C. H.
AU - Postma, Dirkje S.
AU - van Duijn, Cornelia M.
AU - Boezen, H. Marike
AU - Heijmans, Bastiaan T.
AU - Hoen, Peter A. C. T.
AU - van Meurs, Joyce
AU - Isaacs, Aaron
AU - Jansen, Rick
AU - Franke, Lude
AU - Boomsma, Dorret
AU - Pool, Rene
AU - van Dongen, Jenny
AU - Hottenga, Jouke J.
AU - van Greevenbroek, Marleen M. J.
AU - Stehouwer, Coen D. A.
AU - van Der Kallen, Carla J. H.
AU - Schalkwijk, Casper G.
AU - Wijmenga, Cisca
AU - Zhernakova, Sasha
AU - Tigchelaar, Ettje E.
AU - Slagboom, P. Eline
AU - Beekman, Marian
AU - Deelen, Joris
AU - van Heemst, Diana
AU - Veldink, Jan H.
AU - van den Berg, Leonard H.
AU - Hofman, Bert A.
AU - Uitterlinden, Andre G.
AU - Jhamai, P. Mila
AU - Verbiest, Michael
AU - Suchiman, H. Eka D.
AU - Verkerk, Marijn
AU - van Der Breggen, Ruud
AU - van Rooij, Jeroen
AU - Lakenberg, Nico
AU - Mei, Hailiang
AU - van Iterson, Maarten
AU - BIOS Consortium
N1 - Funding Information:
Conflict of Interest statement. L.L. reports personal fees from Boehringer Ingelheim GmbH, non-financial support from Novartis, grants from AstraZeneca, grants and non-financial support from European Respiratory Society and grants and non-financial support from Belgian Respiratory Society, outside the submitted work. DSP reports: The University of Groningen has received money for D.S.P. regarding a grant for research from Astra Zeneca, Chiesi, Genentec, GSK and Roche. Fees for consultancies were given to the University of Groningen by Astra Zeneca, Boehringer Ingelheim, Chiesi, GSK, Takeda and TEVA. All other authors declare they have no actual or potential competing financial interest.
Funding Information:
The LifeLines Biobank initiative has been made possible by funds from FES (Fonds Economische Structuurversterking), SNN (Samenwerkingsverband Noord Nederland) and REP (Ruimtelijke Economisch Programma). The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. The generation and management of the Illumina 450 K methylation array data (EWAS data) for the Rotterdam Study was executed by the Human Genotyping Facility of the Genetic Laboratory of the Department of Internal Medicine, Erasmus MC, the Netherlands. The EWAS data was funded by the Genetic Laboratory of the Department of Internal Medicine, Erasmus MC, and by the Netherlands Organization for Scientific Research (NWO; project number 184021007) and made available as a Rainbow Project (RP3; BIOS) of the Biobanking and Biomolecular Research Infrastructure Netherlands (BBMRI-NL). The Biobank-Based Integrative Omics Studies (BIOS) Consortium is funded by BBMRI-NL, a research infrastructure financed by the Dutch government (NWO 184.021.007).
Funding Information:
Lung Foundation Netherlands (4.1.13.007, 4.113.007 to D.A.v.d.P. and N.A.); Research Foundation—Flanders (postdoctoral fellowship to L.L.).
Publisher Copyright:
© 2019 The Author(s) 2019. Published by Oxford University Press.
PY - 2019/8/1
Y1 - 2019/8/1
N2 - Many workers are daily exposed to occupational agents like gases/fumes, mineral dust or biological dust, which could induce adverse health effects. Epigenetic mechanisms, such as DNA methylation, have been suggested to play a role. We therefore aimed to identify differentially methylated regions (DMRs) upon occupational exposures in never-smokers and investigated if these DMRs associated with gene expression levels. To determine the effects of occupational exposures independent of smoking, 903 never-smokers of the LifeLines cohort study were included. We performed three genome-wide methylation analyses (Illumina 450 K), one per occupational exposure being gases/fumes, mineral dust and biological dust, using robust linear regression adjusted for appropriate confounders. DMRs were identified using comb-p in Python. Results were validated in the Rotterdam Study (233 never-smokers) and methylation-expression associations were assessed using Biobank-based Integrative Omics Study data (n = 2802). Of the total 21 significant DMRs, 14 DMRs were associated with gases/fumes and 7 with mineral dust. Three of these DMRs were associated with both exposures (RPLP1 and LINC02169 (2x)) and 11 DMRs were located within transcript start sites of gene expression regulating genes. We replicated two DMRs with gases/fumes (VTRNA2-1 and GNAS) and one with mineral dust (CCDC144NL). In addition, nine gases/fumes DMRs and six mineral dust DMRs significantly associated with gene expression levels. Our data suggest that occupational exposures may induce differential methylation of gene expression regulating genes and thereby may induce adverse health effects. Given the millions of workers that are exposed daily to occupational exposures, further studies on this epigenetic mechanism and health outcomes are warranted.
AB - Many workers are daily exposed to occupational agents like gases/fumes, mineral dust or biological dust, which could induce adverse health effects. Epigenetic mechanisms, such as DNA methylation, have been suggested to play a role. We therefore aimed to identify differentially methylated regions (DMRs) upon occupational exposures in never-smokers and investigated if these DMRs associated with gene expression levels. To determine the effects of occupational exposures independent of smoking, 903 never-smokers of the LifeLines cohort study were included. We performed three genome-wide methylation analyses (Illumina 450 K), one per occupational exposure being gases/fumes, mineral dust and biological dust, using robust linear regression adjusted for appropriate confounders. DMRs were identified using comb-p in Python. Results were validated in the Rotterdam Study (233 never-smokers) and methylation-expression associations were assessed using Biobank-based Integrative Omics Study data (n = 2802). Of the total 21 significant DMRs, 14 DMRs were associated with gases/fumes and 7 with mineral dust. Three of these DMRs were associated with both exposures (RPLP1 and LINC02169 (2x)) and 11 DMRs were located within transcript start sites of gene expression regulating genes. We replicated two DMRs with gases/fumes (VTRNA2-1 and GNAS) and one with mineral dust (CCDC144NL). In addition, nine gases/fumes DMRs and six mineral dust DMRs significantly associated with gene expression levels. Our data suggest that occupational exposures may induce differential methylation of gene expression regulating genes and thereby may induce adverse health effects. Given the millions of workers that are exposed daily to occupational exposures, further studies on this epigenetic mechanism and health outcomes are warranted.
KW - DECLINE
KW - DISCOVERY
KW - GASES
KW - RISK
KW - FEV1
U2 - 10.1093/hmg/ddz067
DO - 10.1093/hmg/ddz067
M3 - Article
C2 - 31152171
SN - 0964-6906
VL - 28
SP - 2477
EP - 2485
JO - Human Molecular Genetics
JF - Human Molecular Genetics
IS - 15
ER -