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Sinke, L.* ; van Dongen, J.* ; Delerue, T. ; Wilson, R. ; Xia, Y.* ; Beekman, M.* ; Willemsen, G.* ; Gieger, C. ; Herder, C.* ; Koenig, W.* ; Peters, A. ; de Geus, E.J.C.* ; Ordovas, J.M.* ; Bell, J.T.* ; Waldenberger, M. ; Boomsma, D.I.* ; Slagboom, P.E.* ; Heijmans, B.T.*

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

Comm. Biol. 9:242 (2026)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Dna Methylation ; Epigenetics ; Cpg Site ; Methylation ; Disease ; Cytokine ; Epigenesis ; Dna ; Histone; Gene-expression; Transcription; Il-6; Pathway; Differentiation; Induction
ISSN (print) / ISBN 2399-3642
e-ISSN 2399-3642
Zeitschrift Communications Biology
Quellenangaben Band: 9, Heft: 1, Seiten: , Artikelnummer: 242 Supplement: ,
Verlag Springer
Verlagsort London
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Epidemiology (EPI)
Förderungen ZonMw (Netherlands Organisation for Health Research and Development)
Ministry of Economic Affairs | SenterNovem (Senter Novem)
Joint Programming Initiative A healthy diet for a healthy life (JPI A Healthy Diet for a Healthy Life)
Nederlandse Organisatie voor Wetenschappelijk Onderzoek (Netherlands Organisation for Scientific Research)