ArticleThe journals of gerontology. Series A, Biological sciences and medical sciences2021
Creating and Validating a DNA Methylation-Based Proxy for Interleukin-6.
Article in The journals of gerontology. Series A, Biological sciences and medical sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 2 of them syntheses that pooled it.
What it found
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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.
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Who cites it
42 citing papers in PubMed, 2 syntheses or guidelines pooled it, 52 citations in OpenAlex.
- Epigenome-wide association study of circulating interleukin-6 connects DNA methylation to immunometabolic and inflammatory health.Communications biology · 2026Pooled it
- Epigenetic scores of blood-based proteins as biomarkers of general cognitive function and brain health.Clinical epigenetics · 2024Pooled it
- Telehealth Parenting Program and Salivary Epigenetic Biomarkers in Preschool Children With Developmental Delay: NIMHD Social Epigenomics Program.JAMA network open · 2024Trial
- The OmniAge compendium of aging omic biomarkers links mitotic clocks to clonal hematopoiesis and causality.Nature communications · 2026Article
- Protein epigenetic scores derived in neonatal saliva as biomarkers of childhood cognition.Molecular psychiatry · 2026Article
- Strong concordance of DNA methylation measures between venous and capillary blood - Implications for human epigenome studies.iScience · 2026Article
- Epigenetic inflammation signatures and lung cancer risk among never-smoking women: a nested case-control study.medRxiv : the preprint server for health sciences · 2026Article
- An FDA-Approved Tenofovir Alafenamide-Based Antiretroviral Therapy Reduces Biological Age in Healthy Adults: First Human Proof-of-Concept for Retrotransposon-Targeted Gerotherapeutics.medRxiv : the preprint server for health sciences · 2026Article
- Epigenetic age acceleration in young adults with congenital heart disease.Clinical epigenetics · 2026Article
- Blood DNA methylation-predicted plasma protein levels and colorectal cancer survival.Clinical epigenetics · 2026Article
- DNA Methylation Signatures of Systemic Inflammation Are Associated With Brain Volume, Cognitive Trajectories, and Long-Term Dementia Risk.Aging cell · 2025Article
- A novel DNA methylation-based surrogate biomarker for chronic systemic inflammation (Inflammation Latent Variable Methylation Surrogate, InfLaMeS).The journals of gerontology. Series A, Biological sciences and medical sciences · 2025Article
- Variations in Innate Immune Cell Subtypes Correlate with Epigenetic Clocks, Inflammaging and Health Outcomes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Cross-Tissue Specificity of Pediatric DNA Methylation Associated With Cumulative Family Stress.Developmental psychobiology · 2025Article
- Distinct maternal DNA methylation associations with gestational age at early and late-mid term pregnancy in a low- and middle-income country: evaluation of biological, genetic, and psychosocial contributors.BMC pregnancy and childbirth · 2025Article
- Accounting for differences between Infinium MethylationEPIC v2 and v1 in DNA methylation-based tools.Life science alliance · 2025Article
- Cross-omics risk scores of inflammation markers are associated with all-cause mortality: The Canadian Longitudinal Study on Aging.American journal of human genetics · 2025Article
- Toward precision interventions and metrics of inflammaging.Nature aging · 2025Review
- Epigenetic mechanisms underlying variation of IL-6, a well-established inflammation biomarker and risk factor for cardiovascular disease.Atherosclerosis · 2025Article
- Physical activity affects DNA methylation-derived inflammation markers in a community-based Parkinson's disease study.Brain, behavior, & immunity - health · 2025Article
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundStudies evaluating the relationship between chronic inflammation and cognitive functioning have produced heterogeneous results. A potential reason for this is the variability of inflammatory mediators which could lead to misclassifications of individuals' persisting levels of inflammation. DNA methylation (DNAm) has shown utility in indexing environmental exposures and could be leveraged to provide proxy signatures of chronic inflammation.
methodWe conducted an elastic net regression of interleukin-6 (IL-6) in a cohort of 875 older adults (Lothian Birth Cohort 1936; mean age: 70 years) to develop a DNAm-based predictor. The predictor was tested in an independent cohort (Generation Scotland; N = 7028 [417 with measured IL-6], mean age: 51 years).
resultsA weighted score from 35 CpG sites optimally predicted IL-6 in the independent test set (Generation Scotland; R2 = 4.4%, p = 2.1 × 10-5). In the independent test cohort, both measured IL-6 and the DNAm proxy increased with age (serum IL-6: n = 417, β = 0.02, SE = 0.004, p = 1.3 × 10-7; DNAm IL-6 score: N = 7028, β = 0.02, SE = 0.0009, p < 2 × 10-16). Serum IL-6 did not associate with cognitive ability (n = 417, β = -0.06, SE = 0.05, p = .19); however, an inverse association was identified between the DNAm score and cognitive functioning (N = 7028, β = -0.16, SE = 0.02, pFDR < 2 × 10-16).
conclusionsThese results suggest methylation-based predictors can be used as proxies for inflammatory markers, potentially allowing for further insight into the relationship between inflammation and pertinent health outcomes.
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Registered trials
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.