Occupational exposure to gases/fumes and mineral dust affect DNA methylation levels of genes regulating expression

Diana van Der Plaat, Judith M. Vonk, Natalie Terzikhan, Kim de Jong, Maaike de Vries, Sacha La Bastide-van Gemert, Cleo C. van Diemen, Lies Lahousse, Guy Brusselle, Ivana Nedeljkovic, Najaf Amin, Hans Kromhout, Roel C. H. Vermeulen, Dirkje S. Postma, Cornelia M. van Duijn, H. Marike Boezen*, Bastiaan T. Heijmans, Peter A. C. T. Hoen, Joyce van Meurs, Aaron IsaacsRick Jansen, Lude Franke, Dorret Boomsma, Rene Pool, Jenny van Dongen, Jouke J. Hottenga, Marleen M. J. van Greevenbroek, Coen D. A. Stehouwer, Carla J. H. van Der Kallen, Casper G. Schalkwijk, Cisca Wijmenga, Sasha Zhernakova, Ettje E. Tigchelaar, P. Eline Slagboom, Marian Beekman, Joris Deelen, Diana van Heemst, Jan H. Veldink, Leonard H. van den Berg, Bert A. Hofman, Andre G. Uitterlinden, P. Mila Jhamai, Michael Verbiest, H. Eka D. Suchiman, Marijn Verkerk, Ruud van Der Breggen, Jeroen van Rooij, Nico Lakenberg, Hailiang Mei, Maarten van Iterson, BIOS Consortium

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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.

Original languageEnglish
Pages (from-to)2477-2485
Number of pages9
JournalHuman Molecular Genetics
Issue number15
Publication statusPublished - 1 Aug 2019


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