Evidence map›Paper›PMID 27350042›Full record

ArticleGenome biology2016

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 and 25 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Genome biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 papers, 15 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
124citing papers in PubMed, 15 pooled it
13.9field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

124 citing papers in PubMed, 15 syntheses or guidelines pooled it, 197 citations in OpenAlex.

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64 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

35 authors at 6 institutions in 2 countries.

Koen F DekkersMolecular Epidemiology section, Leiden University Medical Center, Einthovenweg 20, Leiden, The Netherlands.
Maarten van ItersonMolecular Epidemiology section, Leiden University Medical Center, Einthovenweg 20, Leiden, The Netherlands.
Roderick C SliekerMolecular Epidemiology section, Leiden University Medical Center, Einthovenweg 20, Leiden, The Netherlands.
Matthijs H MoedMolecular Epidemiology section, Leiden University Medical Center, Einthovenweg 20, Leiden, The Netherlands.
Marc Jan BonderDepartment of Genetics, University of Groningen, University Medical Centre Groningen, Broerstraat 5, Groningen, The Netherlands.
Michiel van GalenDepartment of Human Genetics, Leiden University Medical Center, Einthovenweg 20, Leiden, The Netherlands.
Hailiang MeiSequence Analysis Support Core, Leiden University Medical Center, Einthovenweg 20, Leiden, The Netherlands.
Daria V ZhernakovaDepartment of Genetics, University of Groningen, University Medical Centre Groningen, Broerstraat 5, Groningen, The Netherlands.
Leonard H van den BergDepartment of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Heidelberglaan 100, Utrecht, The Netherlands.
Joris DeelenMolecular Epidemiology section, Leiden University Medical Center, Einthovenweg 20, Leiden, The Netherlands.
Jenny van DongenDepartment of Biological Psychology, VU University Amsterdam, Neuroscience Campus Amsterdam, De Boelelaan 1117, Amsterdam, The Netherlands.
Diana van HeemstDepartment of Gerontology and Geriatrics, Leiden University Medical Center, Einthovenweg 20, Leiden, The Netherlands.
Albert HofmanDepartment of Genetic Epidemiology, ErasmusMC, 's-Gravendijkwal 230, Rotterdam, The Netherlands.
Jouke J HottengaDepartment of Biological Psychology, VU University Amsterdam, Neuroscience Campus Amsterdam, De Boelelaan 1117, Amsterdam, The Netherlands.
Carla J H van der KallenDepartment of Internal Medicine and School for Cardiovascular Diseases (CARIM), Maastricht University Medical Center, P. Debyelaan 25, Maastricht, The Netherlands.
Casper G SchalkwijkDepartment of Internal Medicine and School for Cardiovascular Diseases (CARIM), Maastricht University Medical Center, P. Debyelaan 25, Maastricht, The Netherlands.
Coen D A StehouwerDepartment of Internal Medicine and School for Cardiovascular Diseases (CARIM), Maastricht University Medical Center, P. Debyelaan 25, Maastricht, The Netherlands.
Ettje F TigchelaarDepartment of Genetics, University of Groningen, University Medical Centre Groningen, Broerstraat 5, Groningen, The Netherlands.
André G UitterlindenDepartment of Internal Medicine, ErasmusMC, 's-Gravendijkwal 230, Rotterdam, The Netherlands.
Gonneke WillemsenDepartment of Biological Psychology, VU University Amsterdam, Neuroscience Campus Amsterdam, De Boelelaan 1117, Amsterdam, The Netherlands.
Alexandra ZhernakovaDepartment of Genetics, University of Groningen, University Medical Centre Groningen, Broerstraat 5, Groningen, The Netherlands.
Lude FrankeDepartment of Genetics, University of Groningen, University Medical Centre Groningen, Broerstraat 5, Groningen, The Netherlands.
Peter A C 't HoenDepartment of Human Genetics, Leiden University Medical Center, Einthovenweg 20, Leiden, The Netherlands.
Rick JansenDepartment of Psychiatry, VU University Medical Center, Neuroscience Campus Amsterdam, De Boelelaan 1117, Amsterdam, The Netherlands.
Joyce van MeursDepartment of Internal Medicine, ErasmusMC, 's-Gravendijkwal 230, Rotterdam, The Netherlands.
Dorret I BoomsmaDepartment of Biological Psychology, VU University Amsterdam, Neuroscience Campus Amsterdam, De Boelelaan 1117, Amsterdam, The Netherlands.
Cornelia M van DuijnDepartment of Genetic Epidemiology, ErasmusMC, 's-Gravendijkwal 230, Rotterdam, The Netherlands.
Marleen M J van GreevenbroekDepartment of Internal Medicine and School for Cardiovascular Diseases (CARIM), Maastricht University Medical Center, P. Debyelaan 25, Maastricht, The Netherlands.
Jan H VeldinkDepartment of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Heidelberglaan 100, Utrecht, The Netherlands.
Cisca WijmengaDepartment of Genetics, University of Groningen, University Medical Centre Groningen, Broerstraat 5, Groningen, The Netherlands.
BIOS Consortium
Erik W van ZwetDepartment of Medical Statistics and Bioinformatics, Leiden University Medical Center, Einthovenweg 20, Leiden, The Netherlands.
P Eline SlagboomMolecular Epidemiology section, Leiden University Medical Center, Einthovenweg 20, Leiden, The Netherlands.
J Wouter JukemaDepartment of Cardiology, Leiden University Medical Center, Einthovenweg 20, Leiden, The Netherlands.
Bastiaan T HeijmansMolecular Epidemiology section, Leiden University Medical Center, Einthovenweg 20, Leiden, The Netherlands. bas.heijmans@lumc.nl.
Leiden University Medical Center · NLUniversity Medical Center Groningen · NLAmsterdam Neuroscience · NLErasmus MC · NLMaastricht University · NLHeidelberg University · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCells 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.

resultsThis 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.

conclusionsOur 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.

Indexed as

Epigenesis, GeneticAdolescentAdultAgedAged, 80 and overATP Binding Cassette Transporter, Subfamily G, Member 1Carnitine O-PalmitoyltransferaseCholesterol, HDLCholesterol, LDLCpG IslandsDNA MethylationFemaleGene Expression RegulationGenome, HumanHumansLipid MetabolismATP Binding Cassette Transporter, Subfamily G, Member 1Carnitine O-PalmitoyltransferaseCholesterol, HDLCholesterol, LDLCPT1A protein, humanDHCR24 protein, humanLipidsNerve Tissue ProteinsOxidoreductases Acting on CH-CH Group DonorsSREBF1 protein, humanSterol Regulatory Element Binding Protein 1TriglyceridesDNA methylationGene expressionLipidsMendelian randomization

Identifiers

PMID27350042
PMCPMC4922056
OpenAlexW2467067181

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.