Imperial College London
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DrJamesPeters

Faculty of Medicine, Department of Immunology and Inflammation

Clinical Reader in Rheumatology
 
 
 
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j.peters

 
 
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Location

 

ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Richard:2016:10.1186/s13073-016-0329-5,
author = {Richard, AC and Peters, JE and Lee, JC and Vahedi, G and Schäffer, AA and Siegel, RM and Lyons, PA and Smith, KGC},
doi = {10.1186/s13073-016-0329-5},
journal = {Genome Medicine: medicine in the post-genomic era},
pages = {1--15},
title = {Targeted genomic analysis reveals widespread autoimmune disease association with regulatory variants in the TNF superfamily cytokine signalling network.},
url = {http://dx.doi.org/10.1186/s13073-016-0329-5},
volume = {8},
year = {2016}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BACKGROUND: Tumour 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. METHODS: We 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. RESULTS: Comparison 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 singl
AU  - Richard,AC
AU  - Peters,JE
AU  - Lee,JC
AU  - Vahedi,G
AU  - Schäffer,AA
AU  - Siegel,RM
AU  - Lyons,PA
AU  - Smith,KGC
DO  - 10.1186/s13073-016-0329-5
EP  - 15
PY  - 2016///
SN  - 1756-994X
SP  - 1
TI  - Targeted genomic analysis reveals widespread autoimmune disease association with regulatory variants in the TNF superfamily cytokine signalling network.
T2  - Genome Medicine: medicine in the post-genomic era
UR  - http://dx.doi.org/10.1186/s13073-016-0329-5
UR  - https://www.ncbi.nlm.nih.gov/pubmed/27435189
UR  - https://genomemedicine.biomedcentral.com/articles/10.1186/s13073-016-0329-5
UR  - http://hdl.handle.net/10044/1/74629
VL  - 8
ER  -
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