The identification of blood-derived response eQTLs reveals complex effects of regulatory variants on inflammatory and infectious disease risk.
Hundreds of risk loci for immune mediated inflammatory and infectious diseases have been identified by genome-wide association studies (GWAS). Yet, what causal variants and genes in risk loci underpin the observed associations remains poorly understood for most. The identification of colocalized cis...
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Public Library of Science (PLoS)
2025-04-01
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| Series: | PLoS Genetics |
| Online Access: | https://doi.org/10.1371/journal.pgen.1011599 |
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| author | Claire Liefferinckx David Stern Hélène Perée Jérémie Bottieau Alice Mayer Christophe Dubussy Eric Quertinmont Vjola Tafciu Charlotte Minsart Vyacheslav Petrov Alex Kvasz Wouter Coppieters Latifa Karim Souad Rahmouni Michel Georges Denis Franchimont |
| author_facet | Claire Liefferinckx David Stern Hélène Perée Jérémie Bottieau Alice Mayer Christophe Dubussy Eric Quertinmont Vjola Tafciu Charlotte Minsart Vyacheslav Petrov Alex Kvasz Wouter Coppieters Latifa Karim Souad Rahmouni Michel Georges Denis Franchimont |
| author_sort | Claire Liefferinckx |
| collection | DOAJ |
| description | Hundreds of risk loci for immune mediated inflammatory and infectious diseases have been identified by genome-wide association studies (GWAS). Yet, what causal variants and genes in risk loci underpin the observed associations remains poorly understood for most. The identification of colocalized cis-expression Quantitative Trait Loci (cis-eQTLs) is a promising way to identify candidate causative genes. The catalogue of cis-eQTLs of the immune system is likely incomplete as many cis-eQTLs may be context-specific. We built a large cohort of 406 healthy individuals and expanded the immune cis-regulome through their whole blood transcriptome obtained after stimulation with specific toll-like receptor (TLR) agonists and T-cell receptor (TCR) antagonist. We report three mechanisms that may explain why an eQTL could only be revealed after immune stimulation. More than half of the cis-eQTLs detected in this study would have been overlooked without specific immune stimulations. We then mined this new catalogue of response (r)eQTLs, with public GWAS summary statistics of three diseases through a colocalization approach: inflammatory bowel diseases, rheumatoid arthritis and COVID-19 disease. We identified reQTL-specific colocalizations for risk loci for which no matching eQTL were reported before, revealing interesting new candidate causal genes. |
| format | Article |
| id | doaj-art-352a699a664743429cbd06aa73f3ffc1 |
| institution | OA Journals |
| issn | 1553-7390 1553-7404 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj-art-352a699a664743429cbd06aa73f3ffc12025-08-20T02:19:22ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042025-04-01214e101159910.1371/journal.pgen.1011599The identification of blood-derived response eQTLs reveals complex effects of regulatory variants on inflammatory and infectious disease risk.Claire LiefferinckxDavid SternHélène PeréeJérémie BottieauAlice MayerChristophe DubussyEric QuertinmontVjola TafciuCharlotte MinsartVyacheslav PetrovAlex KvaszWouter CoppietersLatifa KarimSouad RahmouniMichel GeorgesDenis FranchimontHundreds of risk loci for immune mediated inflammatory and infectious diseases have been identified by genome-wide association studies (GWAS). Yet, what causal variants and genes in risk loci underpin the observed associations remains poorly understood for most. The identification of colocalized cis-expression Quantitative Trait Loci (cis-eQTLs) is a promising way to identify candidate causative genes. The catalogue of cis-eQTLs of the immune system is likely incomplete as many cis-eQTLs may be context-specific. We built a large cohort of 406 healthy individuals and expanded the immune cis-regulome through their whole blood transcriptome obtained after stimulation with specific toll-like receptor (TLR) agonists and T-cell receptor (TCR) antagonist. We report three mechanisms that may explain why an eQTL could only be revealed after immune stimulation. More than half of the cis-eQTLs detected in this study would have been overlooked without specific immune stimulations. We then mined this new catalogue of response (r)eQTLs, with public GWAS summary statistics of three diseases through a colocalization approach: inflammatory bowel diseases, rheumatoid arthritis and COVID-19 disease. We identified reQTL-specific colocalizations for risk loci for which no matching eQTL were reported before, revealing interesting new candidate causal genes.https://doi.org/10.1371/journal.pgen.1011599 |
| spellingShingle | Claire Liefferinckx David Stern Hélène Perée Jérémie Bottieau Alice Mayer Christophe Dubussy Eric Quertinmont Vjola Tafciu Charlotte Minsart Vyacheslav Petrov Alex Kvasz Wouter Coppieters Latifa Karim Souad Rahmouni Michel Georges Denis Franchimont The identification of blood-derived response eQTLs reveals complex effects of regulatory variants on inflammatory and infectious disease risk. PLoS Genetics |
| title | The identification of blood-derived response eQTLs reveals complex effects of regulatory variants on inflammatory and infectious disease risk. |
| title_full | The identification of blood-derived response eQTLs reveals complex effects of regulatory variants on inflammatory and infectious disease risk. |
| title_fullStr | The identification of blood-derived response eQTLs reveals complex effects of regulatory variants on inflammatory and infectious disease risk. |
| title_full_unstemmed | The identification of blood-derived response eQTLs reveals complex effects of regulatory variants on inflammatory and infectious disease risk. |
| title_short | The identification of blood-derived response eQTLs reveals complex effects of regulatory variants on inflammatory and infectious disease risk. |
| title_sort | identification of blood derived response eqtls reveals complex effects of regulatory variants on inflammatory and infectious disease risk |
| url | https://doi.org/10.1371/journal.pgen.1011599 |
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