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Lyons, Paul A; Peters, James E; Alberici, Federico; Liley, James; Coulson, Richard M. R.; Astle, William; Baldini, Chiara; Bonatti, Francesco; Cid, Maria C; Elding, Heather; Emmi, Giacomo; Epplen, Jörg; Guillevin, Loïc; Jayne, David R. W.; Jiang, Tao; Gunnarsson, Iva; Lamprecht, Peter; Leslie, Stephen; Little, Mark A.; Martorana, Davide; Moosig, Frank; Neumann, Thomas; Ohlsson, Sophie; Quickert, Stefanie; [...]

Genome-wide association study of eosinophilic granulomatosis with polyangiitis reveals genomic loci stratified by ANCA status

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  • Medientyp: E-Artikel
  • Titel: Genome-wide association study of eosinophilic granulomatosis with polyangiitis reveals genomic loci stratified by ANCA status
  • Beteiligte: Lyons, Paul A; Peters, James E; Alberici, Federico; Liley, James; Coulson, Richard M. R.; Astle, William; Baldini, Chiara; Bonatti, Francesco; Cid, Maria C; Elding, Heather; Emmi, Giacomo; Epplen, Jörg; Guillevin, Loïc; Jayne, David R. W.; Jiang, Tao; Gunnarsson, Iva; Lamprecht, Peter; Leslie, Stephen; Little, Mark A.; Martorana, Davide; Moosig, Frank; Neumann, Thomas; Ohlsson, Sophie; Quickert, Stefanie; [...]
  • Erschienen: Springer Science and Business Media LLC, 2019
  • Erschienen in: Nature Communications
  • Sprache: Englisch
  • DOI: 10.1038/s41467-019-12515-9
  • ISSN: 2041-1723
  • Schlagwörter: General Physics and Astronomy ; General Biochemistry, Genetics and Molecular Biology ; General Chemistry ; Multidisciplinary
  • Entstehung:
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  • Beschreibung: <jats:title>Abstract</jats:title><jats:p>Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare inflammatory disease of unknown cause. 30% of patients have anti-neutrophil cytoplasmic antibodies (ANCA) specific for myeloperoxidase (MPO). Here, we describe a genome-wide association study in 676 EGPA cases and 6809 controls, that identifies 4 EGPA-associated loci through conventional case-control analysis, and 4 additional associations through a conditional false discovery rate approach. Many variants are also associated with asthma and six are associated with eosinophil count in the general population. Through Mendelian randomisation, we show that a primary tendency to eosinophilia contributes to EGPA susceptibility. Stratification by ANCA reveals that EGPA comprises two genetically and clinically distinct syndromes. MPO+ ANCA EGPA is an eosinophilic autoimmune disease sharing certain clinical features and an <jats:italic>HLA-DQ</jats:italic> association with MPO+ ANCA-associated vasculitis, while ANCA-negative EGPA may instead have a mucosal/barrier dysfunction origin. Four candidate genes are targets of therapies in development, supporting their exploration in EGPA.</jats:p>
  • Zugangsstatus: Freier Zugang