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 (2×)) 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.
© The Author(s) 2019. Published by Oxford University Press.
Overview publication
| Title | Occupational exposure to gases/fumes and mineral dust affect DNA methylation levels of genes regulating expression. |
| Date | August 1st, 2019 |
| Issue name | Human molecular genetics |
| Issue number | v28.15:2477-2485 |
| DOI | 10.1093/hmg/ddz067 |
| PubMed | 31152171 |
| Authors | |
| Info | BIOS Consortium, Heijmans BT, 't Hoen PAC, van Meurs J, Isaacs A, Jansen R, Franke L, Boomsma DI, Pool R, van Dongen J, Hottenga JJ, van Greevenbroek MM, Stehouwer CDA, van der Kallen CJH, Schalkwijk CG, Wijmenga C, Franke L, Zhernakova S, Tigchelaar EF, Slagboom PE, Beekman M, Deelen J, van Heemst D, Veldink JH, van den Berg LH, van Duijn CM, Hofman BA, Isaacs A, Uitterlinden AG, van Meurs J, Jhamai PM, Verbiest M, Suchiman HED, Verkerk M, der Breggen RV, van Rooij J, Lakenberg N, Mei H, van Iterson M, van Galen M, Bot J, Zhernakova DV, Jansen R, Van't Hof P, Deelen P, Nooren I, 't Hoen PAC, Heijmans BT, Moed M, Franke L, Vermaat M, Zhernakova DV, Luijk R, Bonder MJ, van Iterson M, Deelen P, van Dijk F, van Galen M, Arindrarto W, Kielbasa SM, Swertz MA, van Zwet EW, Jansen R, Hoen PB, Heijmans BT, Heijmans BT, 't Hoen PAC, van Meurs J, Isaacs A, Jansen R, Franke L, Boomsma DI, Pool R, van Dongen J, Hottenga JJ, van Greevenbroek MM, Stehouwer CDA, van der Kallen CJH, Schalkwijk CG, Wijmenga C, Franke L, Zhernakova S, Tigchelaar EF, Slagboom PE, Beekman M, Deelen J, van Heemst D, Veldink JH, van den Berg LH, van Duijn CM, Hofman BA, Isaacs A, Uitterlinden AG, van Meurs J, Jhamai PM, Verbiest M, Suchiman HED, Verkerk M, van der Breggen R, van Rooij J, Lakenberg N, Mei H, van Iterson M, van Galen M, Bot J, Zhernakova DV, Jansen R, van 't Hof P, Deelen P, Nooren I, 't Hoen PAC, Heijmans BT, Moed M, Franke L, Vermaat M, Zhernakova DV, Luijk R, Bonder MJ, van Iterson M, Deelen P, van Dijk F, van Galen M, Arindrarto W, Kielbasa SM, Swertz MA, van Zwet EW, Jansen R, 't Hoen PB, Heijmans BT |
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