Evidence map›Paper›PMID 41639309›Full record

SynthesisCommunications biology2026

Epigenome-wide association study of circulating interleukin-6 connects DNA methylation to immunometabolic and inflammatory health.

Lucy Sinke, Jenny van Dongen, Thomas Delerue, Rory Wilson, Yujing Xia, Marian Beekman, Gonneke Willemsen, Christian Gieger, Christian Herder, Wolfgang Koenig and 8 more

Abstract readMeta-Analysis
In one paragraph

Synthesis in Communications biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors.

Lucy SinkeMolecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands. l.j.sinke@lacdr.leidenuniv.nl.ORCID http://orcid.org/0000-0002-9209-1266
Jenny van DongenDepartment of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Thomas DelerueResearch Unit Molecular Epidemiology, Institute of Epidemiology, Helmholtz Munich, German Research Center for Environmental Health, Neuherberg, Germany.
Rory WilsonResearch Unit Molecular Epidemiology, Institute of Epidemiology, Helmholtz Munich, German Research Center for Environmental Health, Neuherberg, Germany.
Yujing XiaDepartment of Twin Research and Genetic Epidemiology, King's College London, London, UK.
Marian BeekmanMolecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands.ORCID http://orcid.org/0000-0003-0585-6206
Gonneke WillemsenDepartment of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Christian GiegerResearch Unit Molecular Epidemiology, Institute of Epidemiology, Helmholtz Munich, German Research Center for Environmental Health, Neuherberg, Germany.ORCID http://orcid.org/0000-0001-6986-9554
Christian HerderInstitute for Clinical Diabetology, German Diabetes Center (Deutsches Diabetes-Zentrum/DDZ), Leibniz Center for Diabetes Research at Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.
Wolfgang KoenigGerman Center for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany.ORCID http://orcid.org/0000-0002-2064-9603
Annette PetersResearch Unit Molecular Epidemiology, Institute of Epidemiology, Helmholtz Munich, German Research Center for Environmental Health, Neuherberg, Germany.ORCID http://orcid.org/0000-0001-6645-0985
Eco J C de GeusDepartment of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.ORCID http://orcid.org/0000-0001-6022-2666
José M OrdovasUSDA ARS, Nutrition and Genomics Laboratory, JM-USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA.
Jordana T BellDepartment of Twin Research and Genetic Epidemiology, King's College London, London, UK.ORCID http://orcid.org/0000-0002-3858-5986
Melanie WaldenbergerResearch Unit Molecular Epidemiology, Institute of Epidemiology, Helmholtz Munich, German Research Center for Environmental Health, Neuherberg, Germany.
Dorret I BoomsmaDepartment of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
P Eline SlagboomMolecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands.ORCID http://orcid.org/0000-0002-2875-4723
Bastiaan T HeijmansMolecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands. b.t.heijmans@lumc.nl.ORCID http://orcid.org/0000-0001-5918-0534

Funding

Integration of Genomics & Transcriptomics in Normal Twins & Major DepressionRC2MH089951 · NIMH · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SULLIVAN, PATRICK F · 2009 to 2010
$6.5M
Genomics of Developmental Trajectories in TwinsRC2MH089995 · NIMH · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · PI HUDZIAK, JAMES J. · 2009 to 2010
$3.8M
Collaborative Study of Genetics of Dizygotic TwinningR01HD042157 · NICHD · QUEENSLAND INSTITUTE OF MEDICAL RESEARCH · PI MONTGOMERY, GRANT W · 2002 to 2006
$2.0M
Major Depression: Stage 1 Genomewide Association in Population-Based SamplesR01MH081802 · NIMH · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SULLIVAN, PATRICK F · 2007 to 2007
$138k
EPA EP-C-15-001Joint Programming Initiative A healthy diet for a healthy life (JPI A Healthy Diet for a Healthy Life) 01EA1902AMinistry of Economic Affairs | SenterNovem (Senter Novem) IGE01014Ministry of Economic Affairs | SenterNovem (Senter Novem) IGE05007Nederlandse Organisatie voor Wetenschappelijk Onderzoek (Netherlands Organisation for Scientific Research) 184.021.007Nederlandse Organisatie voor Wetenschappelijk Onderzoek (Netherlands Organisation for Scientific Research) 184.034.019NICHD NIH HHS R01 HD042157NIMH NIH HHS R01 MH081802NIMH NIH HHS RC2 MH089951NIMH NIH HHS RC2 MH089995ZonMw (Netherlands Organisation for Health Research and Development) 529051021ZonMw (Netherlands Organisation for Health Research and Development) 91109032
6 · The paper itself

Abstract

Interleukin-6 (IL-6) drives metabolic and inflammatory processes central to disease. Current knowledge implicates epigenetic mechanisms in the regulation of these pathways, including through the methylation of CpG sites. This blood-based meta-analysis of three cohorts (n = 4,361) identifies 401 IL-6-associated CpGs enriched in regulatory regions and linked to key immunometabolic genes, including AIM2, MTOR, and IL6R. Three complementary causal inference approaches support most sites as responding to IL-6, with SOCS3 (Suppressor of Cytokine Signalling 3) methylation statistically mediating inflammatory bowel disease risk. Notably, one CpG connected to NFATC2IP (Nuclear Factor of Activated T-cells 2 Interacting Protein) plausibly influences both IL-6 production and multiple immunometabolic conditions, including body mass index and type 2 diabetes. Collectively, our results map the DNA methylation landscape surrounding circulating IL-6 levels and unveil directional effects and distinct functional relationships between epigenetics and inflammation.

Indexed as

DNA MethylationEpigenesis, GeneticEpigenomeInflammationInterleukin-6CpG IslandsGenome-Wide Association StudyHumansIL6 protein, humanInterleukin-6

Identifiers

PMID41639309
PMCPMC12905258

What OpenQuestion holds

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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 OpenQuestion graph.