ArticleGenome medicine2016
Targeted genomic analysis reveals widespread autoimmune disease association with regulatory variants in the TNF superfamily cytokine signalling network.
Article in Genome medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 21 citations in OpenAlex.
- Genetic testing guides therapy in children with refractory cytopenias.Haematologica · 2026Article
- Gene regulatory network integration with multi-omics data enhances survival predictions in cancer.Briefings in bioinformatics · 2025Article
- Nonlinear Dynamics of TNFR1 and TNFR2 Expression on Immune Cells: Genetic and Age-Related Aspects of Inflamm-Aging Mechanisms.Biomedicines · 2025Article
- TNF Superfamily and ILC2 Activation in Asthma.Biomolecules · 2024Review
- Low-dose IL-2 reduces IL-21Nature communications · 2022Article
- Re-emerging concepts of immune dysregulation in autism spectrum disorders.Frontiers in psychiatry · 2022Review
- Regulatory SNPs: Altered Transcription Factor Binding Sites Implicated in Complex Traits and Diseases.International journal of molecular sciences · 2021Review
- Potential Molecular Mechanism of TNF Superfamily-Related Genes in Glioblastoma Multiforme Based on Transcriptome and Epigenome.Frontiers in neurology · 2021Article
- Socioeconomic Deprivation, Adverse Childhood Experiences and Medical Disorders in Adulthood: Mechanisms and Associations.Molecular neurobiology · 2019Review
- Reduced monocyte and macrophage TNFSF15/TL1A expression is associated with susceptibility to inflammatory bowel disease.PLoS genetics · 2018Article
- Type 3 innate lymphoid cell-derived lymphotoxin prevents microbiota-dependent inflammation.Cellular & molecular immunology · 2018Article
- Beyond TNF: TNF superfamily cytokines as targets for the treatment of rheumatic diseases.Nature reviews. Rheumatology · 2017Review
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundTumour necrosis factor (TNF) superfamily cytokines and their receptors regulate diverse immune system functions through a common set of signalling pathways. Genetic variants in and expression of individual TNF superfamily cytokines, receptors and signalling proteins have been associated with autoimmune and inflammatory diseases, but their interconnected biology has been largely unexplored.
methodsWe took a hypothesis-driven approach using available genome-wide datasets to identify genetic variants regulating gene expression in the TNF superfamily cytokine signalling network and the association of these variants with autoimmune and autoinflammatory disease. Using paired gene expression and genetic data, we identified genetic variants associated with gene expression, expression quantitative trait loci (eQTLs), in four peripheral blood cell subsets. We then examined whether eQTLs were dependent on gene expression level or the presence of active enhancer chromatin marks. Using these eQTLs as genetic markers of the TNF superfamily signalling network, we performed targeted gene set association analysis in eight autoimmune and autoinflammatory disease genome-wide association studies.
resultsComparison of TNF superfamily network gene expression and regulatory variants across four leucocyte subsets revealed patterns that differed between cell types. eQTLs for genes in this network were not dependent on absolute gene expression levels and were not enriched for chromatin marks of active enhancers. By examining autoimmune disease risk variants among our eQTLs, we found that risk alleles can be associated with either increased or decreased expression of co-stimulatory TNF superfamily cytokines, receptors or downstream signalling molecules. Gene set disease association analysis revealed that eQTLs for genes in the TNF superfamily pathway were associated with six of the eight autoimmune and autoinflammatory diseases examined, demonstrating associations beyond single genome-wide significant hits.
conclusionsThis systematic analysis of the influence of regulatory genetic variants in the TNF superfamily network reveals widespread and diverse roles for these cytokines in susceptibility to a number of immune-mediated diseases.
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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.