Blood lipids influence DNA methylation in circulating cells

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...

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Bibliographic Details
Published in:Genome Biology 2016-06, Vol.17 (1), p.138-138, Article 138
Main Authors: Dekkers, Koen F, van Iterson, Maarten, Slieker, Roderick C, Moed, Matthijs H, Bonder, Marc Jan, van Galen, Michiel, Mei, Hailiang, Zhernakova, Daria V, van den Berg, Leonard H, Deelen, Joris, van Dongen, Jenny, van Heemst, Diana, Hofman, Albert, Hottenga, Jouke J, van der Kallen, Carla J H, Schalkwijk, Casper G, Stehouwer, Coen D A, Tigchelaar, Ettje F, Uitterlinden, André G, Willemsen, Gonneke, Zhernakova, Alexandra, Franke, Lude, 't Hoen, Peter A C, Jansen, Rick, van Meurs, Joyce, Boomsma, Dorret I, van Duijn, Cornelia M, van Greevenbroek, Marleen M J, Veldink, Jan H, Wijmenga, Cisca, van Zwet, Erik W, Slagboom, P Eline, Jukema, J Wouter, Heijmans, Bastiaan T
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
Aged, 80 and over
Arteriosclerosis
Atherosclerosis
ATP Binding Cassette Transporter, Subfamily G, Member 1 - blood
ATP Binding Cassette Transporter, Subfamily G, Member 1 - genetics
Bioinformatics
Blood levels
Carnitine O-Palmitoyltransferase - blood
Carnitine O-Palmitoyltransferase - genetics
Cholesterol
Cholesterol, HDL - blood
Cholesterol, HDL - genetics
Cholesterol, LDL - blood
Cholesterol, LDL - genetics
Consortia
CpG islands
CpG Islands - genetics
Deoxyribonucleic acid
DNA
DNA methylation
DNA Methylation - genetics
Epigenesis, Genetic
External stimuli
Female
Gene Expression Regulation - genetics
Genome, Human
Genomes
Genomics
Genotype & phenotype
High density lipoprotein
Humans
Lipid metabolism
Lipid Metabolism - genetics
Lipids
Lipids - blood
Lipids - genetics
Low density lipoprotein
Male
Middle Aged
Nerve Tissue Proteins - blood
Nerve Tissue Proteins - genetics
Oxidoreductases Acting on CH-CH Group Donors - blood
Oxidoreductases Acting on CH-CH Group Donors - genetics
Pleiotropy
Quality control
Ribonucleic acid
RNA
Standard deviation
Sterol Regulatory Element Binding Protein 1 - blood
Sterol Regulatory Element Binding Protein 1 - genetics
Studies
Triglycerides
Triglycerides - blood
Triglycerides - genetics
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Summary: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. 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. 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.
ISSN:1474-760X
1474-7596
1474-760X
DOI:10.1186/s13059-016-1000-6