Genetic architecture of adaptive immune system identifies key immune regulators
The immune system is highly diverse, but characterization of its genetic architecture has lagged behind the vast progress made by genome-wide association studies (GWASs) of emergent diseases. Our GWAS for 54 functionally relevant phenotypes of the adaptive immune system in 489 healthy individuals id...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
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Elsevier
2018
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| _version_ | 1826256870639140864 |
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| author | Lagou, V Garcia-Perez, J Smets, I Van Horebeek, L Vandebergh, M Chen, L Mallants, K Prezzemolo, T Hilven, K Humblet-Baron, S Moisse, M Van Damme, P Boeckxstaens, G Bowness, P Dubois, B Dooley, J Liston, A Goris, A |
| author_facet | Lagou, V Garcia-Perez, J Smets, I Van Horebeek, L Vandebergh, M Chen, L Mallants, K Prezzemolo, T Hilven, K Humblet-Baron, S Moisse, M Van Damme, P Boeckxstaens, G Bowness, P Dubois, B Dooley, J Liston, A Goris, A |
| author_sort | Lagou, V |
| collection | OXFORD |
| description | The immune system is highly diverse, but characterization of its genetic architecture has lagged behind the vast progress made by genome-wide association studies (GWASs) of emergent diseases. Our GWAS for 54 functionally relevant phenotypes of the adaptive immune system in 489 healthy individuals identifies eight genome-wide significant associations explaining 6%–20% of variance. Coding and splicing variants in PTPRC and COMMD10 are involved in memory T cell differentiation. Genetic variation controlling disease-relevant T helper cell subsets includes RICTOR and STON2 associated with Th2 and Th17, respectively, and the interferon-lambda locus controlling regulatory T cell proliferation. Early and memory B cell differentiation stages are associated with variation in LARP1B and SP4. Finally, the latrophilin family member ADGRL2 correlates with baseline pro-inflammatory interleukin-6 levels. Suggestive associations reveal mechanisms of autoimmune disease associations, in particular related to pro-inflammatory cytokine production. Pinpointing these key human immune regulators offers attractive therapeutic perspectives. |
| first_indexed | 2024-03-06T18:09:08Z |
| format | Journal article |
| id | oxford-uuid:0262fa28-63af-4864-86a9-e5fb215b4aa2 |
| institution | University of Oxford |
| last_indexed | 2024-03-06T18:09:08Z |
| publishDate | 2018 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oxford-uuid:0262fa28-63af-4864-86a9-e5fb215b4aa22022-03-26T08:40:29ZGenetic architecture of adaptive immune system identifies key immune regulatorsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:0262fa28-63af-4864-86a9-e5fb215b4aa2Symplectic Elements at OxfordElsevier2018Lagou, VGarcia-Perez, JSmets, IVan Horebeek, LVandebergh, MChen, LMallants, KPrezzemolo, THilven, KHumblet-Baron, SMoisse, MVan Damme, PBoeckxstaens, GBowness, PDubois, BDooley, JListon, AGoris, AThe immune system is highly diverse, but characterization of its genetic architecture has lagged behind the vast progress made by genome-wide association studies (GWASs) of emergent diseases. Our GWAS for 54 functionally relevant phenotypes of the adaptive immune system in 489 healthy individuals identifies eight genome-wide significant associations explaining 6%–20% of variance. Coding and splicing variants in PTPRC and COMMD10 are involved in memory T cell differentiation. Genetic variation controlling disease-relevant T helper cell subsets includes RICTOR and STON2 associated with Th2 and Th17, respectively, and the interferon-lambda locus controlling regulatory T cell proliferation. Early and memory B cell differentiation stages are associated with variation in LARP1B and SP4. Finally, the latrophilin family member ADGRL2 correlates with baseline pro-inflammatory interleukin-6 levels. Suggestive associations reveal mechanisms of autoimmune disease associations, in particular related to pro-inflammatory cytokine production. Pinpointing these key human immune regulators offers attractive therapeutic perspectives. |
| spellingShingle | Lagou, V Garcia-Perez, J Smets, I Van Horebeek, L Vandebergh, M Chen, L Mallants, K Prezzemolo, T Hilven, K Humblet-Baron, S Moisse, M Van Damme, P Boeckxstaens, G Bowness, P Dubois, B Dooley, J Liston, A Goris, A Genetic architecture of adaptive immune system identifies key immune regulators |
| title | Genetic architecture of adaptive immune system identifies key immune regulators |
| title_full | Genetic architecture of adaptive immune system identifies key immune regulators |
| title_fullStr | Genetic architecture of adaptive immune system identifies key immune regulators |
| title_full_unstemmed | Genetic architecture of adaptive immune system identifies key immune regulators |
| title_short | Genetic architecture of adaptive immune system identifies key immune regulators |
| title_sort | genetic architecture of adaptive immune system identifies key immune regulators |
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