Genome-wide association study of eosinophilic granulomatosis with polyangiitis reveals genomic loci stratified by ANCA status
Creators: name: Lyons, Paul A
name: Peters, James E
name: Alberici, Federico
name: Liley, James
name: Coulson, Richard M. R.
name: Astle, William
name: Baldini, Chiara
name: Bonatti, Francesco
name: Cid, Maria C
name: Elding, Heather
name: Emmi, Giacomo
name: Epplen, Jörg
name: Guillevin, Loïc
name: Jayne, David R. W.
name: Jiang, Tao
name: Gunnarsson, Iva
name: Lamprecht, Peter
name: Leslie, Stephen
name: Little, Mark A.
name: Martorana, Davide
name: Moosig, Frank
name: Neumann, Thomas
name: Ohlsson, Sophie
name: Quickert, Stefanie
name: Ramirez, Giuseppe A.
name: Rewerska, Barbara
name: Schett, Georg
name: Sinico, Renato A.
name: Szczeklik, Wojciech
name: Tesar, Vladimir
name: Vukcevic, Damjan
name: Terrier, Benjamin
name: Watts, Richard A
name: Vaglio, Augusto
name: Holle, Julia U
name: Wallace, Chris
name: Smith, Kenneth G. C.
name: Akil, Mohammed
name: Barratt, Jonathan
name: Basu, Neil
name: Butterworth, Adam S.
name: Bruce, Ian
name: Clarkson, Michael
name: Conlon, Niall
name: DasGupta, Bhaskar
name: Doulton, Timothy W. R.
name: Espígol-Frigolé, Georgina
name: Flossmann, Oliver
name: Gabrielli, Armando
name: Gasior, Jolanta
name: Gregorini, Gina
name: Guida, Giuseppe
name: Hernández-Rodríguez, José
name: Hruskova, Zdenka
name: Hudson, Amy
name: Knight, Ann
name: Lanyon, Peter
name: Luqmani, Raashid
name: Magliano, Malgorzata
name: Manfredi, Angelo A.
name: Marguerie, Christopher
name: Maritati, Federica
name: Marvisi, Chiara
name: McHugh, Neil J.
name: Molloy, Eamonn
name: Motyer, Allan
name: Mukhtyar, Chetan
name: Padyukov, Leonid
name: Pesci, Alberto
name: Prieto-Gonzalez, Sergio
name: Ramentol-Sintas, Marc
name: Reis, Petra
name: Roccatello, Dario
name: Rovere-Querini, Patrizia
name: Salvarani, Carlo
name: Santarsia, Francesca
name: Solans-Laque, Roser
name: Soranzo, Nicole
name: Taylor, Jo
name: Wessels, Julie
name: Zwerina, Jochen
Publisher: name: Apollo - University of Cambridge Repository
Year: 2019
Subjects: Article
/631/208/205/2138
/631/250/38
/631/250/248
/692/4023/1670
/45
/45/43
article

description: Abstract: 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.