Cross-phenotype analysis of Immunochip data identifies KDM4C as a relevant locus for the development of systemic vasculitis. Issue 4 (27th January 2018)

• Record Type: Journal Article
• Authors: Ortiz-Fernández, Lourdes; Carmona, Francisco David; López-Mejías, Raquel; González-Escribano, Maria Francisca; Lyons, Paul A; Morgan, Ann W; Sawalha, Amr H; Merkel, Peter A; Smith, Kenneth G C; González-Gay, Miguel A; Martín, Javier
• Other Names: author non-byline.; Alegre-Sancho Juan J author non-byline.; Blanco Ricardo author non-byline.; Callejas José Luis author non-byline.; Caminal-Montero Luis author non-byline.; Castañeda Santos author non-byline.; Cid M C author non-byline.; Corbera-Bellalta Marc author non-byline.; Miguel Eugenio de author non-byline.; Díaz-López J Bernardino author non-byline.; Escalante Begoña author non-byline.; Mateo Patricia Fanlo author non-byline.; Fernández-Gutiérrez Benjamín author non-byline.; Fernández-Nebro Antonio author non-byline.; García-Villanueva María Jesús author non-byline.; Gómez-Vaquero Carmen author non-byline.; Grau Elena author non-byline.; Rojas Mercedes Guijarro author non-byline.; Hernández-Rodríguez José author non-byline.; Hidalgo-Conde Ana author non-byline.; López-Longo Francisco J author non-byline.; Madroñero Vuelta Ana Belén author non-byline.; Marí-Alfonso Begoña author non-byline.; Martínez Lina author non-byline.; Martínez-Berriochoa Agustín author non-byline.; Martínez-Taboada Víctor Manuel author non-byline.; Martínez-Zapico Aleida author non-byline.; Miranda-Filloy José A author non-byline.; Monfort Jordi author non-byline.; Morado Inmaculada C author non-byline.; Narváez Javier author non-byline.; Ordóñez-Cañizares M Carmen author non-byline.; Ortego-Centeno Norberto author non-byline.; Pérez-Conesa Mercedes author non-byline.; Prieto-González Sergio author non-byline.; Ramentol-Sintas Marc author non-byline.; Raya Enrique author non-byline.; Fernández Raquel Ríos author non-byline.; Rodríguez-Rodríguez Luis author non-byline.; Román José A author non-byline.; Sáez-Comet Luis author non-byline.; Sánchez-Martín Julio author non-byline.; Sánchez-Pernaute Olga author non-byline.; Solans Roser author non-byline.; Sopeña Bernardo author non-byline.; Tío Laura author non-byline.; Unzurrunzaga Ainhoa author non-byline.; Vicente Esther F author non-byline.; Dasgupta Bhaskar author non-byline.; Eyre Stephen author non-byline.; Green Michael author non-byline.; Gough Andrew author non-byline.; Hordon Lesley author non-byline.; Jarret Stephen author non-byline.; Kamath Sanjeet author non-byline.; Levy Sarah author non-byline.; Mackie Sarah L author non-byline.; Patel Yusuf author non-byline.; Pease Colin T author non-byline.; Taylor John C author non-byline.; Watts Richard author non-byline.; Worthington Jane author non-byline.; Alibaz-Oner Fatima author non-byline.; Akar Servet author non-byline.; Akkoc Nurullah author non-byline.; Aksu Kenan author non-byline.; Ates Askin author non-byline.; Aydin Sibel Z author non-byline.; Bıcakcıgil Muge author non-byline.; Cefle Ayse author non-byline.; Cobankara Veli author non-byline.; Coit Patrick author non-byline.; Dalkilic Ediz author non-byline.; Direskeneli Haner author non-byline.; Duzgun Nurşen author non-byline.; Erken Eren author non-byline.; Fresko Izzet author non-byline.; Inanc Murat author non-byline.; Kamali Sevil author non-byline.; Karaaslan Yasar author non-byline.; Karadag Omer author non-byline.; Kaşifoğlu Timuçin author non-byline.; Keser Gokhan author non-byline.; Kısacık Bünyamin author non-byline.; Kiraz Sedat author non-byline.; Onat Ahmet Mesut author non-byline.; Onen Fatos author non-byline.; Ozbalkan Zeynep author non-byline.; Ozer Hüseyin T E author non-byline.; Ozturk Mehmet A author non-byline.; Pamuk Ömer N author non-byline.; Saruhan-Direskeneli Güher author non-byline.; Seyahi Emire author non-byline.; Tunc Ercan author non-byline.; Yazici Ayten author non-byline.; Yentür Sibel P author non-byline.; Carette Simon author non-byline.; Chung Sharon A author non-byline.; Cuthbertson David author non-byline.; Forbess Lindsay J author non-byline.; Hoffman Gary S author non-byline.; Khalidi Nader A author non-byline.; Koening Curry L author non-byline.; Langford Carol A author non-byline.; Mcalear Carol A author non-byline.; Mckinnon-Maksimowicz Kathleen author non-byline.; Merkel Peter A author non-byline.; Monach Paul A author non-byline.; Moreland Larry author non-byline.; Pagnoux Christian author non-byline.; Seo Philip author non-byline.; Spiera Robert author non-byline.; Sreih Antoine G author non-byline.; Warrington Kenneth J author non-byline.; Ytterberg Steven R author non-byline.; Aragües Maximiliano author non-byline.; Blanco-Madrigal Juan María author non-byline.; Argila Diego de author non-byline.; Galíndez-Aguirregoikoa Eva author non-byline.; Genre Fernanda author non-byline.; Luque Manuel León author non-byline.; Llorca Javier author non-byline.; Mijares Verónica author non-byline.; Parejo Antonio Navas author non-byline.; Pina Trinitario author non-byline.; Remuzgo-Martínez Sara author non-byline.; Rubio Esteban author non-byline.; Sevilla-Perez Belén author non-byline.; Ubilla Begoña author non-byline.; Brenchley Paul author non-byline.; Chaundrhy Afzal N author non-byline.; Clayton David G author non-byline.; Deloukas Panos author non-byline.; Harper Lorraine author non-byline.; Jayne David RW author non-byline.; Little Mark A author non-byline.; Padmanabhan Sandosh author non-byline.; Pusey Charles D author non-byline.; Rayner Tim F author non-byline.; Salamana Alan D author non-byline.; Savage Caroline O author non-byline.; Trived Sapna author non-byline.; Watts Richard A author non-byline.;
• Is Part Of: Annals of the rheumatic diseases. Volume 77:Issue 4(2018)
• Page Start: 589
• Page End: 595
• Publication Date: 2018-01-27
• Subjects: systemic sclerosis -- autoantibodies -- outcomes research; Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2017-212372
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Objetive: Systemic vasculitides represent a heterogeneous group of rare complex diseases of the blood vessels with a poorly understood aetiology. To investigate the shared genetic component underlying their predisposition, we performed the first cross-phenotype meta-analysis of genetic data from different clinically distinct patterns of vasculitis. Methods: Immunochip genotyping data from 2465 patients diagnosed with giant cell arteritis, Takayasu's arteritis, antineutrophil cytoplasmic antibody-associated vasculitis or IgA vasculitis as well as 4632 unaffected controls were analysed to identify common susceptibility loci for vasculitis development. The possible functional consequences of the associated variants were interrogated using publicly available annotation data. Results: The strongest association signal corresponded with an intergenic polymorphism located between HLA-DQB1 and HLA-DQA2 (rs6932517, P=4.16E-14, OR=0.74). This single nucleotide polymorphism is in moderate linkage disequilibrium with the disease-specific human leucocyte antigen (HLA) class II associations of each type of vasculitis and could mark them. Outside the HLA region, we identified the KDM4C gene as a common risk locus for vasculitides (highest peak rs16925200, P=6.23E-07, OR=1.75). This gene encodes a histone demethylase involved in the epigenetic control of gene expression. Conclusions: Through a combined analysis of Immunochip data, we have identified KDM4C as a new risk gene shared between systemic vasculitides, consistent with the increasing evidences of the crucial role that the epigenetic mechanisms have in the development of complex immune-mediated conditions.