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oai:recercat.cat:2072/4549232026-04-14T04:48:23Zcom_2072_98col_2072_378192

urn:hdl:2072/454923 Genome-wide association study of eosinophilic granulomatosis with polyangiitis reveals genomic loci stratified by ANCA status Lyons, Paul A. Peters, James E. Alberici, Federico Liley, James Coulson, Richard M. R. Astle, William Baldini, Chiara Bonatti, Francesco Cid, María Cinta 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, Stefan Ramirez, Giuseppe A. Rewerska, Barbara Schett, George Sinico, Renato A. Szczeklik, Wojciech Tesar, Vladimir Vukcevic, Damjan Akil, Mohammed Barratt, Jonathan Basu, Neil Butterworth, Adam Bruce, Ian Clarkson, Michael Conlon, Niall DasGupta, Bhaskar Doulton, Timothy W. R. Espígol-Frigolé, Georgina Flossmann, Oliver Gabrielli, Armando Gasior, Jolanta Gregorini, Gina Guida, Giuseppe Hernández Rodríguez, José Hruskova, Zdenka Hudson, Amy Knight, Ann Lanyon, Peter Luqmani, Raashid Magliano, Malgorzata Manfredi, Angelo A. Marguerie, Christopher Maritati, Federica Marvisi, Chiara McHugh, Neil J. Molloy, Eaminn Motyer, Allan Mukhtyar, Chetan Padyukov, Leonid Pesci, Alberto Prieto-Gonzalez, Sergio Ramentol-Sintas, Marc Reis, Petra Roccatello, Dario Rovere-Querini, Patrizia Salvarani, Carlo Santarsia, Francesca Solans, Roser Soranzo, Nicole Taylor, Jo Wessels, Julie Zwerina, Jochen Terrier, Benjamin Watts, Richard A. Vaglio, Augusto Holle, Julia U. Wallace, Chris Smith, Kenneth G. C. Universitat Autònoma de Barcelona Antibodies, Antineutrophil Cytoplasmic Eosinophils Genetic Association Studies Genetic Loci Genetic Predisposition to Disease Genome-Wide Association Study Granulomatosis with Polyangiitis Humans Mendelian Randomization Analysis 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 HLA-DQ 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. 2019 Article Ministerio de Economía y Competitividad SAF2017-88275-R Instituto de Salud Carlos III PI18/00461 Nature communications ; Vol. 10 Núm. 1 (january 2019), p. 5120 open access Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. https://creativecommons.org/licenses/by/4.0/