1. Genome-wide association study of systemic sclerosis identifies **CD247** as a new susceptibility locus
- Author
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Alexander Kreuter, Gabriela Riemekasten, Patricia Carreira, Timothy R D J Radstake, Rajan Madhok, María Francisca González-Escribano, Filip De Keyser, Nico Hunzelmann, Ariane L. Herrick, Monique Hinchcliff, Ruben van 't Slot, Rafaella Scorza, Benedicte A. Lie, Jose Ezequiel Martin, Roger Hesselstrand, Pravitt Gourh, Laura K. Hummers, Lorenzo Beretta, Jun Ying, Fredrick M. Wigley, Annemie J. Schuerwegh, Hans P. Kiener, Vanessa Smith, Jaap M van Laar, Paolo Airò, Paul G. Shiels, Blanca Rueda, Norberto Ortego-Centeno, Carmen P. Simeon, Filemon K. Tan, Anna Maria Hoffmann-Vold, Shervin Assassi, Shih-Feng Weng, Annet Italiaander, Alexandre E. Voskuyl, J. Lee Nelson, Fredric Houssiau, Olga Y. Gorlova, Jane Worthington, Torsten Witte, Piet L. C. M. van Riel, Younghun Han, Maureen D. Mayes, Lars Klareskog, Peter K. Gregersen, Jasper C A Broen, Christopher I. Amos, Sandeep K. Agarwal, Leonid Padykov, Frank C. Arnett, Marieke J H Coenen, Rene Westhovens, Roel A. Ophoff, Bobby P. C. Koeleman, Meng May Chee, Behrooz Z. Alizadeh, Elfride De Baere, Annette Lee, Rogelio Palomino-Morales, Madelon C. Vonk, Javier Martín, John Varga, Miguel A. Gonzalez-Gay, and UCL - SSS/IREC/RUMA - Pôle de Pathologies rhumatismales
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Adult ,Male ,Systemic disease ,CD3 Complex ,CD247 ,Population ,Antigens, CD3 - genetics ,Genome-wide association study ,Single-nucleotide polymorphism ,Biology ,Auto-immunity, transplantation and immunotherapy [N4i 4] ,Article ,Cohort Studies ,Genomic disorders and inherited multi-system disorders [IGMD 3] ,Molecular epidemiology [NCEBP 1] ,Risk Factors ,Odds Ratio ,Genetics ,medicine ,Humans ,Genetic Predisposition to Disease ,Health care ethics [NCEBP 5] ,education ,skin and connective tissue diseases ,Aged ,education.field_of_study ,Scleroderma, Systemic ,Lupus erythematosus ,integumentary system ,Multiple sclerosis ,Scleroderma, Systemic - genetics ,Middle Aged ,medicine.disease ,Europe ,Evaluation of complex medical interventions [NCEBP 2] ,Case-Control Studies ,Immunology ,Female ,cd4 t-cells lupus-erythematosus functional polymorphism japanese population cd3-zeta expression complex risk scleroderma mechanisms phenotype ,Human medicine ,Infection and autoimmunity [NCMLS 1] ,IRF5 ,Genome-Wide Association Study - Abstract
4 páginas, 2 figuras, 2 tablas.-- Spanish Scleroderma Group., Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis of the skin and internal organs that leads to profound disability and premature death. To identify new SSc susceptibility loci, we conducted the first genome-wide association study in a population of European ancestry including a total of 2,296 individuals with SSc and 5,171 controls. Analysis of 279,621 autosomal SNPs followed by replication testing in an independent case-control set of European ancestry (2,753 individuals with SSc (cases) and 4,569 controls) identified a new susceptibility locus for systemic sclerosis at CD247 (1q22–23, rs2056626, P = 2.09 × 10−7 in the discovery samples, P = 3.39 × 10−9 in the combined analysis). Additionally, we confirm and firmly establish the role of the MHC (P = 2.31 × 10−18), IRF5 (P = 1.86 × 10−13) and STAT4 (P = 3.37 × 10−9) gene regions as SSc genetic risk factors., This work was supported by the following grants: T.R.D.J.R. was funded by the VIDI laureate from the Dutch Association of Research (NWO) and Dutch Arthritis Foundation (National Reumafonds). J.M. was funded by GEN-FER from the Spanish Society of Rheumatology, SAF2009-11110 from the Spanish Ministry of Science, CTS-4977 from Junta de Andalucía, Spain and in part by Redes Temáticas de Investigación Cooperativa Sanitaria Program, RD08/0075 (RIER) from Instituto de Salud Carlos III (ISCIII), Spain (J.M.). R.B. is supported by the I3P Consejo Superior de Investigaciones Científicas program funded by the 'Fondo Social Europeo'. B.Z.A. is supported by the Netherlands Organization for Health Research and Development (ZonMW grant 016.096.121). B.K. is supported by the Dutch Diabetes Research Foundation (grant 2008.40.001) and the Dutch Arthritis Foundation (Reumafonds, grant NR 09-1-408). Genotyping of the Dutch control samples was sponsored by US National Insitutes of Mental Health funding, R01 MH078075 (R.O.A.). The German controls were from the PopGen biobank (to B.K.).
- Published
- 2010