Analysis of the common genetic component of large-vessel vasculitides through a meta-Immunochip strategy
Authors: Carmona F. David , Coit Patrick , Saruhan-Direskeneli Güher , Hernández-Rodríguez José , Cid María C. , Solans Roser , Castañeda Santos , Vaglio Augusto , Direskeneli Haner , Merkel Peter A. , Boiardi Luigi , Salvarani Carlo , González-Gay Miguel A. , Martín Javier , Sawalha Amr H. ,   Spanish GCA Study Group, Martínez-Berriochoa Agustín , Unzurrunzaga Ainhoa , Hidalgo-Conde Ana , Vuelta Ana Belén Madroñero , Fernández-Nebro Antonio , Ordóñez-Cañizares M. Carmen , Fernández-Gutiérrez Benjamín , Rodríguez-Rodríguez Luis , Escalante Begoña , Marí-Alfonso Begoña , Sopeña Bernardo , Gómez-Vaquero Carmen , Raya Enrique , Grau Elena , Román José A. , Vicente Esther F. , de Miguel Eugenio , López-Longo Francisco J. , Martínez Lina , Morado Inmaculada C. , Díaz-López J. Bernardino , Caminal-Montero Luis , Martínez-Zapico Aleida , Narváez Javier , Monfort Jordi , Tío Laura , Miranda-Filloy José A. , Sánchez-Martín Julio , Alegre-Sancho Juan J. , Sáez-Comet Luis , Pérez-Conesa Mercedes , Corbera-Bellalta Marc , Ramentol-Sintas Marc , García-Villanueva María Jesús , Guijarro Rojas Mercedes , Ortego-Centeno Norberto , Ríos Fernández Raquel , Callejas José Luis , Sanchez Pernaute Olga , Fanlo Mateo Patricia , Blanco Ricardo , Prieto-González Sergio , Martínez-Taboada Víctor Manuel ,   Italian GCA Study Group, Soriano Alessandra , Lunardi Claudio , Gianfreda Davide , Santilli Daniele , Bonatti Francesco , Muratore Francesco , Pazzola Giulia , Addimanda Olga , Emmi Giacomo , Ramirez Giuseppe A. , Beretta Lorenzo , Govoni Marcello , Cimmino Marco A. ,   Turkish Takayasu Study Group, Mesut Onat Ahmet , Cefle Ayse , Yazici Ayten , Kısacık Bünyamin , Dalkilic Ediz , Seyahi Emire , Fresko Izzet , Tunc Ercan , Erken Eren , TE Ozer Hüseyin , Aksu Kenan , Keser Gokhan , Ozturk Mehmet A. , Bıcakcıgil Muge , Duzgun Nurşen , Karadag Omer , Kiraz Sedat , Pamuk Ömer N. , Akar Servet , Onen Fatos , Akkoc Nurullah , Kamali Sevil , Inanc Murat , Yentür Sibel P. , Aydin Sibel Z. , Alibaz-Oner Fatma , Kaşifoğlu Timuçin , Cobankara Veli , Ozbalkan Zeynep , Ates Askin , Karaaslan Yasar ,   Vasculitis Clinical Research Consortium, Carette Simon , Chung Sharon A. , Cuthbertson David , Forbess Lindsay J. , Hoffman Gary S. , Khalidi Nader A. , Koening Curry L. , Langford Carol A. , McAlear Carol A. , McKinnon-Maksimowicz Kathleen , Monach Paul A. , Moreland Larry , Pagnoux Christian , Seo Philip , Spiera Robert , Sreih Antoine G. , Warrington Kenneth J. , Ytterberg Steven R. 
Published: March 2017

AbstractGiant cell arteritis (GCA) and Takayasu’s arteritis (TAK) are major forms of large-vessel vasculitis (LVV) that share clinical features. To evaluate their genetic similarities, we analysed Immunochip genotyping data from 1,434 LVV patients and 3,814 unaffected controls. Genetic pleiotropy was also estimated. The HLA region harboured the main disease-specific associations. GCA was mostly associated with class II genes (HLA-DRB1/HLA-DQA1) whereas TAK was mostly associated with class I genes (HLA-B/MICA). Both the statistical significance and effect size of the HLA signals were considerably reduced in the cross-disease meta-analysis in comparison with the analysis of GCA and TAK separately. Consequently, no significant genetic correlation between these two diseases was observed when HLA variants were tested. Outside the HLA region, only one polymorphism located nearby the IL12B gene surpassed the study-wide significance threshold in the meta-analysis of the discovery datasets (rs755374, P = 7.54E-07; ORGCA = 1.19, ORTAK = 1.50). This marker was confirmed as novel GCA risk factor using four additional cohorts (PGCA = 5.52E-04, ORGCA = 1.16). Taken together, our results provide evidence of strong genetic differences between GCA and TAK in the HLA. Outside this region, common susceptibility factors were suggested, especially within the IL12B locus.