A Large-Scale Genetic Analysis Reveals a Strong Contribution of the HLA Class II Region to Giant Cell Arteritis Susceptibility
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1 The American Journal of Human Genetics Supplemental Data A Large-Scale Genetic Analysis Reveals a Strong Contribution of the HLA Class II Region to Giant Cell Arteritis Susceptibility F. David Carmona, Sarah L. Mackie, Jose-Ezequiel Martín, John C. Taylor, Augusto Vaglio, Stephen Eyre, Lara Bossini-Castillo, Santos Castañeda, María C. Cid, José Hernández-Rodríguez, Sergio Prieto-González, Roser Solans, Marc Ramentol-Sintas, M. Francisca González-Escribano, Lourdes Ortiz-Fernández, Inmaculada C. Morado, Javier Narváez, José A. Miranda-Filloy, Spanish GCA Group, Lorenzo Beretta, Claudio Lunardi, Marco A. Cimmino, Davide Gianfreda, Daniele Santilli, Giuseppe A. Ramirez, Alessandra Soriano, Francesco Muratore, Giulia Pazzola, Olga Addimanda, Cisca Wijmenga, Torsten Witte, Jan H. Schirmer, Frank Moosig, Verena Schönau, Andre Franke, Øyvind Palm, Øyvind Molberg, Andreas P. Diamantopoulos, Simon Carette, David Cuthbertson, Lindsy J. Forbess, Gary S. Hoffman, Nader A. Khalidi, Curry L. Koening, Carol A. Langford, Carol A. McAlear, Larry Moreland, Paul A. Monach, Christian Pagnoux, Philip Seo, Robert Spiera, Antoine G. Sreih, Kenneth J. Warrington, Steven R. Ytterberg, Peter K. Gregersen, Colin T. Pease, Andrew Gough, Michael Green, Lesley Hordon, Stephen Jarrett, Richard Watts, Sarah Levy, Yusuf Patel, Sanjeet Kamath, Bhaskar Dasgupta, Jane Worthington, Bobby P.C. Koeleman, Paul I.W. de Bakker, Jennifer H. Barrett, Carlo Salvarani, Peter A. Merkel, Miguel A. González-Gay, Ann W. Morgan, and Javier Martín
2 Figure S1. Plot of the first and second principal components of the study cohorts and the populations in HapMap phase 3. *Populations included in this study. HapMap populations: ASW, African ancestry in Southwest USA; CEU, Utah residents with Northern and Western European ancestry from the CEPH collection; CHB, Han Chinese in Beijing, China; CHD, Chinese in Metropolitan Denver, Colorado; GIH, Gujarati Indians in Houston, Texas; JPT, Japanese in Tokyo, Japan; LWK, Luhya in Webuye, Kenya; MEX, Mexican ancestry in Los Angeles, California; MKK, Maasai in Kinyawa, Kenya; TSI, Tuscans in Italy; YRI, Yoruba in Ibadan, Nigeria.
3 Figure S2. Manhattan plot representation of the Immunochip results for the independent populations. The log10 of the logistic regression test P-values are plotted against its physical chromosomal position. The results of the analyses including and excluding rare variants are shown. The red line represents the genome-wide level of significance (P<5 10-8).
4 Figure S3. Imputation accuracy in this study of classical HLA-DQα1, HLA-DRβ1, and HLA-B alleles.
5 Figure S4. Manhattan plot representation of the omnibus test results. The log10 of the combined omnibus test P-values are plotted against the physical chromosomal positions of the centre of codon. The red line represents the genome-wide level of significance (P< ). Each analysed HLA gene is represented with a different colour.
6 Figure S5. Regional plots of previously associated candidate genes with giant cell arteritis in the overall meta-analysis. Red arrows point to the lead variants of the gene (highlighted in violet). A) Interleukin 12 receptor beta 2 (IL12RB2); B) Fc fragment of IgG low affinity IIa/IIIa receptor (FCGR2A/ FCGR3A) genomic region (r 2 is referred to rs ); C) Interleukin 10 (IL10) genomic region; D) Interleukin 4 (IL4) genomic region; E) Tumor necrosis factor (TNF) genomic region; F) Interleukin 17A (IL17A) genomic region; G) Interleukin 6 (IL6) genomic region; H) Toll-like receptor 4 (TLR4) genomic region; I) Interferon gamma (IFNG) genomic region; J) NLR family pyrin domain containing 1 (NLRP1) genomic region in the overall meta-analysis; K) nitric oxide synthase 2 inducible (NOS2) genomic region; L) Intercellular adhesion molecule 1 (ICAM1) genomic region; M) Matrix metallopeptidase 9 (MMP9) genomic region.
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13 Supplemental note. Spanish GCA Group Members Agustín Martínez Berriochoa, Department of Internal Medicine, Hospital de Cruces, Barakaldo (Spain). Ainhoa Unzurrunzaga, Department of Internal Medicine, Hospital de Galdakano, Vizcaya (Spain). Ana Hidalgo-Conde, Department of Internal Medicine, Hospital Universitario Virgen de la Victoria, Málaga (Spain). Ana Belén Madroñero Vuelta, Departament of Internal Medicine, Hospital Universitario Arnau de Vilanova, Lleida (Spain). Antonio Fernández-Nebro and María Carmen Ordóñez Cañizares, Rheumatology Department, Hospital Carlos Haya, Málaga (Spain). Begoña Escalante, Department of Internal Medicine, Hospital Clínico Universitario Lozano Blesa, Zaragoza (Spain). Begoña Marí-Alfonso, Department of Internal Medicine, Corporació Sanitaria Parc Taulí, Instituto Universitario Parc Taulí, UAB, Sabadell, Barcelona (Spain). Bernardo Sopeña, Department of Internal Medicine, Complejo Hospitalario Universitario de Vigo Xeral-Chuvi (Spain). César Magro and Enrique Raya, Department of Rheumatology, Hospital Clínico Universitario San Cecilio, Granada (Spain). Elena Grau and José Andrés Román, Department of Rheumatology, Hospital Universitario y Politécnico La Fe, Valencia (Spain). Eugenio de Miguel, Department of Rheumatology, Hospital Universitario de La Paz, Madrid (Spain). Francisco Javier López-Longo and Lina Martínez, Department of Rheumatology, Hospital General Universitario Gregorio Marañón, Madrid (Spain). Carmen Gómez-Vaquero, Department of Rheumatology, Hospital Universitario de Bellvitge-IDIBELL, L'Hospitalet de Llobregat, Barcelona (Spain). Benjamín Fernández-Gutiérrez and Luis Rodríguez-Rodríguez, Department of Rheumatology, Hospital Clínico San Carlos, Madrid (Spain). J. Bernardino Díaz López, Luis Caminal-Montero and Aleida Martínez Zapico, Department of Internal Medicine, Hospital Central de Asturias, Oviedo (Spain). Jordi Monfort and Laura Tío, Department of Rheumatology, Grup de recerca cel lular en inflamació i cartílag. IMIM (Institut de Recerca Hospital del Mar), Barcelona (Spain). Julio Sánchez-Martín, Department of Rheumatology, Hospital Universitario 12 de Octubre, Madrid, Spain (Spain). Juan José Alegre Sancho, Departament of Reumatology, Hospital Universitario Doctor Peset, Valencia (Spain). Luis Sáez-Comet and Mercedes Pérez-Conesa, Department of Internal Medicine, Hospital Universitario Miguel Servet, Zaragoza (Spain). Marc Corbera-Bellalta, Vasculitis Research Unit, Department of Autoimmune and Systemic Diseases, Hospital Clinic, University of Barcelona, Centre de Recerca Biomèdica Cellex (IDIBAPS), Barcelona (Spain). María Jesús García-Villanueva, Department of Rheumatology, Hospital Ramón y Cajal, Madrid (Spain). M. Encarnación Fernández-Contreras, Department of Rheumatology, Hospital La Princesa, Madrid, (Spain). Olga Sanchez Pernaute, Rheumatology Division, Fundación Jiménez Díaz, Universidad Autónoma, Madrid (Spain). Ricardo Blanco, Department of Rheumatology, Hospital Universitario Marqués de Valdecilla, IDIVAL, Santander (Spain). Norberto Ortego-Centeno, Raquel Ríos Fernández and José Luis Callejas, Department of Internal Medicine, Hospital Clínico San Cecilio, Granada (Spain). Patricia Fanlo Mateo, Department of Internal Medicine, Hospital Virgen del Camino, Pamplona (Spain). Víctor Manuel Martínez-Taboada, Rheumatology Department, Hospital Universitario Marqués de Valdecilla, Facultad de Medicina, Universidad de Cantabria, Santander (Spain).
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