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Updated: Feb 6, 2026

Sample Preparation to Bioinformatics Analysis of DNA Methylation: Association Strategy for Obesity and Related Trait Studies
Published on: May 6, 2022
Epigenome-wide association study of circulating interleukin-6 connects DNA methylation to immunometabolic and
Lucy Sinke1, Jenny van Dongen2,3, Thomas Delerue4
1Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands. l.j.sinke@lacdr.leidenuniv.nl.
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.
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