ArticleGenome medicine2020
Multi-method genome- and epigenome-wide studies of inflammatory protein levels in healthy older adults.
Article in Genome medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 2 of them syntheses that pooled it.
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Who cites it
38 citing papers in PubMed, 2 syntheses or guidelines pooled it, 70 citations in OpenAlex.
- Inflammatory cytokines are associated with stroke and risk factors of cerebrovascular diseases: a Mendelian randomization study.Mammalian genome : official journal of the International Mammalian Genome Society · 2025Pooled it
- Pooled it
- Exploring the role of inflammatory cytokines in obesity-mediated MASLD development and drug target identification.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Mechanism-First Psychobiotics: Fermented Vegetables, Dairy, and Soy for Depression and Anxiety.International journal of molecular sciences · 2026Review
- Epigenome-wide association study of blood proteome in the Atherosclerosis Risk in Communities study.HGG advances · 2026Article
- Borderline acceleration in blood epigenetic age of unclear biological importance in knee osteoarthritis progression: Specimens and data from the Osteoarthritis Initiative and Johnston County Osteoarthritis Project.Osteoarthritis and cartilage · 2026Article
- Blood DNA methylation-predicted plasma protein levels and colorectal cancer survival.Clinical epigenetics · 2026Article
- Integrative analysis of DNA methylation and inflammatory protein biomarkers in hypertension.Frontiers in immunology · 2026Article
- Evaluating the Causal Roles of Matrix Metalloproteinases in Metabolic Syndrome: A Mendelian Randomization Study Highlighting MMP12 in Blood Pressure Regulation.Genetics research · 2026Article
- Methylome-wide association studies and epigenetic biomarker development for 133 mass spectrometry-assessed circulating proteins in 14,671 Generation Scotland participants.Genome biology · 2025Article
- Variations in Innate Immune Cell Subtypes Correlate with Epigenetic Clocks, Inflammaging and Health Outcomes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Co-Expression of MHC-II and ANXA1: Mediators of PD-1/PD-L1 Therapy Resistance in Breast Cancer.Cancer reports (Hoboken, N.J.) · 2025Article
- Exploring the role of CD13 and inflammatory factors in radiation enteritis: insights from high-throughput proteomics and Mendelian randomization analysis.Discover oncology · 2025Article
- A novel framework to build saliva-based DNA methylation biomarkers: Quantifying systemic chronic inflammation as a case study.Aging cell · 2025Article
- DNA methylation-predicted plasma protein levels and breast cancer risk.Breast cancer research : BCR · 2025Article
- Influence of Altered Immune-Inflammatory Axis on the Risk of Osteomyelitis and Its Network Interaction Effect in European Population.Mediators of inflammation · 2025Article
- A methylome-wide association study of major depression with out-of-sample case-control classification and trans-ancestry comparison.Nature. Mental health · 2025Article
- Plasma TREM2 levels, alcohol consumption, and liver enzymes in patients with alcohol use disorder: a sex-dependent relationship involving MS4A6A genetic polymorphism.Journal of proteomics and genomics research · 2025Article
- Bivariate genome-wide association study of circulating fibrinogen and C-reactive protein levels.Journal of thrombosis and haemostasis : JTH · 2024Article
- The Genetic Variants Influencing Hypertension Prevalence Based on the Risk of Insulin Resistance as Assessed Using the Metabolic Score for Insulin Resistance (METS-IR).International journal of molecular sciences · 2024Article
Corrections and comments
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Authors and funding
19 authors at 7 institutions in 5 countries.
Funding
Abstract
backgroundThe molecular factors which control circulating levels of inflammatory proteins are not well understood. Furthermore, association studies between molecular probes and human traits are often performed by linear model-based methods which may fail to account for complex structure and interrelationships within molecular datasets.
methodsIn this study, we perform genome- and epigenome-wide association studies (GWAS/EWAS) on the levels of 70 plasma-derived inflammatory protein biomarkers in healthy older adults (Lothian Birth Cohort 1936; n = 876; Olink® inflammation panel). We employ a Bayesian framework (BayesR+) which can account for issues pertaining to data structure and unknown confounding variables (with sensitivity analyses using ordinary least squares- (OLS) and mixed model-based approaches).
resultsWe identified 13 SNPs associated with 13 proteins (n = 1 SNP each) concordant across OLS and Bayesian methods. We identified 3 CpG sites spread across 3 proteins (n = 1 CpG each) that were concordant across OLS, mixed-model and Bayesian analyses. Tagged genetic variants accounted for up to 45% of variance in protein levels (for MCP2, 36% of variance alone attributable to 1 polymorphism). Methylation data accounted for up to 46% of variation in protein levels (for CXCL10). Up to 66% of variation in protein levels (for VEGFA) was explained using genetic and epigenetic data combined. We demonstrated putative causal relationships between CD6 and IL18R1 with inflammatory bowel disease and between IL12B and Crohn's disease.
conclusionsOur data may aid understanding of the molecular regulation of the circulating inflammatory proteome as well as causal relationships between inflammatory mediators and disease.
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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.