Blood lipids influence DNA methylation in circulating cells

Koen F. Dekkers, Maarten van Iterson, Roderick C. Slieker, Matthijs H. Moed, Marc Jan Bonder, Michiel van Galen, Hailiang Mei, Daria V. Zhernakova, Leonard H. van den Berg, Joris Deelen, Jenny van Dongen, Diana van Heemst, Albert Hofman, Jouke J. Hottenga, Carla J. H. van der Kallen, Casper G. Schalkwijk, Coen D. A. Stehouwer, Ettje F. Tigchelaar, Andre G. Uitterlinden, Gonneke WillemsenAlexandra Zhernakova, Lude Franke, Peter A. C. 't Hoen, Rick Jansen, Joyce van Meurs, Dorret I. Boomsma, Cornelia M. van Duijn, Marleen M. J. van Greevenbroek, Jan H. Veldink, Cisca Wijmenga, Erik W. van Zwet, P. Eline Slagboom, J. Wouter Jukema, Bastiaan T. Heijmans*, BIOS Consortium

*Corresponding author voor dit werk

OnderzoeksoutputAcademicpeer review

144 Citaten (Scopus)
336 Downloads (Pure)

Samenvatting

Background: Cells can be primed by external stimuli to obtain a long-term epigenetic memory. We hypothesize that long-term exposure to elevated blood lipids can prime circulating immune cells through changes in DNA methylation, a process that may contribute to the development of atherosclerosis. To interrogate the causal relationship between triglyceride, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol levels and genome-wide DNA methylation while excluding confounding and pleiotropy, we perform a stepwise Mendelian randomization analysis in whole blood of 3296 individuals.

Results: This analysis shows that differential methylation is the consequence of inter-individual variation in blood lipid levels and not vice versa. Specifically, we observe an effect of triglycerides on DNA methylation at three CpGs, of LDL cholesterol at one CpG, and of HDL cholesterol at two CpGs using multivariable Mendelian randomization. Using RNA-seq data available for a large subset of individuals (N = 2044), DNA methylation of these six CpGs is associated with the expression of CPT1A and SREBF1 (for triglycerides), DHCR24 (for LDL cholesterol) and ABCG1 (for HDL cholesterol), which are all key regulators of lipid metabolism.

Conclusions: Our analysis suggests a role for epigenetic priming in end-product feedback control of lipid metabolism and highlights Mendelian randomization as an effective tool to infer causal relationships in integrative genomics data.

Originele taal-2English
Artikelnummer138
Aantal pagina's12
TijdschriftGenome Biology
Volume17
DOI's
StatusPublished - 27-jun.-2016

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  • Additional file 11: of Blood lipids influence DNA methylation in circulating cells

    van Meurs, J. (Contributor), van den Berg, L. H. (Contributor), van Galen, M. (Contributor), Franke, L. (Contributor), Hottenga, J. J. (Contributor), Zhernakova, S. (Contributor), Uitterlinden, A. G. (Contributor), Wijmenga, C. (Contributor), van Dongen, J. (Contributor), van der Kallen, C. J. H. (Contributor), Willemsen, G. (Contributor), Zhernakova, D. (Contributor), Mei, H. (Contributor), Jukema, J. W. (Contributor), van Zwet, E. W. (Contributor), Dekkers, K. F. (Contributor), Jansen, R. (Contributor), Deelen, J. (Contributor), Stehouwer, C. D. A. (Contributor), Tigchelaar - Feenstra, E. (Contributor), Slieker, R. C. (Contributor), Heijmans, B. T. (Contributor), van Iterson, M. (Contributor), Boomsma, D. I. (Contributor), van Greevenbroek, M. M. J. (Contributor), van Duijn, C. M. (Contributor), 't Hoen, P. A. C. (Contributor), van Heemst, D. (Contributor), Bonder, M. J. (Contributor), Slagboom, P. E. (Contributor), Schalkwijk, C. G. (Contributor), Moed, M. H. (Contributor), Hofman, A. (Contributor) & Veldink, J. H. (Contributor), University of Groningen, 14-dec.-2016

    Dataset

  • Additional file 5: of Blood lipids influence DNA methylation in circulating cells

    Slieker, R. C. (Contributor), van Galen, M. (Contributor), Veldink, J. H. (Contributor), van Dongen, J. (Contributor), Uitterlinden, A. G. (Contributor), van den Berg, L. H. (Contributor), Franke, L. (Contributor), Hottenga, J. J. (Contributor), Stehouwer, C. D. A. (Contributor), van Zwet, E. W. (Contributor), Zhernakova, D. (Contributor), Slagboom, P. E. (Contributor), van Meurs, J. (Contributor), Mei, H. (Contributor), Willemsen, G. (Contributor), Bonder, M. J. (Contributor), Jukema, J. W. (Contributor), Moed, M. H. (Contributor), Dekkers, K. F. (Contributor), Hofman, A. (Contributor), van Heemst, D. (Contributor), 't Hoen, P. A. C. (Contributor), Tigchelaar - Feenstra, E. (Contributor), van Duijn, C. M. (Contributor), Zhernakova, S. (Contributor), van der Kallen, C. J. H. (Contributor), Boomsma, D. I. (Contributor), Schalkwijk, C. G. (Contributor), Heijmans, B. T. (Contributor), Jansen, R. (Contributor), Wijmenga, C. (Contributor), van Greevenbroek, M. M. J. (Contributor), van Iterson, M. (Contributor) & Deelen, J. (Contributor), University of Groningen, 14-dec.-2016

    Dataset

  • Additional file 8: of Blood lipids influence DNA methylation in circulating cells

    Veldink, J. H. (Contributor), Boomsma, D. I. (Contributor), van Duijn, C. M. (Contributor), Zhernakova, D. (Contributor), Moed, M. H. (Contributor), van Zwet, E. W. (Contributor), Mei, H. (Contributor), Zhernakova, S. (Contributor), van Heemst, D. (Contributor), van Iterson, M. (Contributor), Deelen, J. (Contributor), van Dongen, J. (Contributor), Bonder, M. J. (Contributor), Hottenga, J. J. (Contributor), Tigchelaar - Feenstra, E. (Contributor), van Meurs, J. (Contributor), Uitterlinden, A. G. (Contributor), Heijmans, B. T. (Contributor), Slagboom, P. E. (Contributor), van Greevenbroek, M. M. J. (Contributor), Jansen, R. (Contributor), 't Hoen, P. A. C. (Contributor), Wijmenga, C. (Contributor), Dekkers, K. F. (Contributor), van Galen, M. (Contributor), Willemsen, G. (Contributor), Franke, L. (Contributor), Jukema, J. W. (Contributor), van der Kallen, C. J. H. (Contributor), van den Berg, L. H. (Contributor), Stehouwer, C. D. A. (Contributor), Hofman, A. (Contributor), Schalkwijk, C. G. (Contributor) & Slieker, R. C. (Contributor), University of Groningen, 14-dec.-2016

    Dataset

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