Genome-wide association study of systemic sclerosis identifies CD247 as a new susceptibility locus

• Published in: Nature genetics Vol. 42; no. 5; pp. 426 - 429
• Main Authors: Radstake, Timothy R D J, Gorlova, Olga, Rueda, Blanca, Martin, Jose-Ezequiel, Alizadeh, Behrooz Z, Palomino-Morales, Rogelio, Coenen, Marieke J, Vonk, Madelon C, Voskuyl, Alexandre E, Schuerwegh, Annemie J, Broen, Jasper C, van Riel, Piet L C M, van 't Slot, Ruben, Italiaander, Annet, Ophoff, Roel A, Riemekasten, Gabriela, Hunzelmann, Nico, Simeon, Carmen P, Ortego-Centeno, Norberto, González-Gay, Miguel A, González-Escribano, María F, Airo, Paolo, van Laar, Jaap, Herrick, Ariane, Worthington, Jane, Hesselstrand, Roger, Smith, Vanessa, de Keyser, Filip, Houssiau, Fredric, Chee, Meng May, Madhok, Rajan, Shiels, Paul, Westhovens, Rene, Kreuter, Alexander, Kiener, Hans, de Baere, Elfride, Witte, Torsten, Padykov, Leonid, Klareskog, Lars, Beretta, Lorenzo, Scorza, Rafaella, Lie, Benedicte A, Hoffmann-Vold, Anna-Maria, Carreira, Patricia, Varga, John, Hinchcliff, Monique, Gregersen, Peter K, Lee, Annette T, Ying, Jun, Han, Younghun, Weng, Shih-Feng, Amos, Christopher I, Wigley, Fredrick M, Hummers, Laura, Nelson, J Lee, Agarwal, Sandeep K, Assassi, Shervin, Gourh, Pravitt, Tan, Filemon K, Koeleman, Bobby P C, Arnett, Frank C, Martin, Javier, Mayes, Maureen D
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.05.2010; Nature Publishing Group
• Subjects: 631/208/205/2138; 631/208/457; 631/208/727/2000; 692/699/1670/122/1801; Adult; Aged; Agriculture; Animal Genetics and Genomics; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer Research; Case-Control Studies; CD3 Complex - genetics; Clinical Medicine; Cohort Studies; Europe; Female; Fundamental and applied biological sciences. Psychology; Gene Function; Genetic aspects; Genetic Predisposition to Disease; Genetic susceptibility; Genetics; Genetics of eukaryotes. Biological and molecular evolution; Genome-Wide Association Study; Human Genetics; Humans; Klinisk medicin; letter; Male; Medical and Health Sciences; Medical research; Medical sciences; Medicin och hälsovetenskap; Middle Aged; Odds Ratio; Reumatologi och inflammation; Rheumatology and Autoimmunity; Risk Factors; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Science; Scleroderma (Disease); Scleroderma, Systemic - genetics; Studies; Systemic scleroderma; United States; Immunopathology; Connective tissue disease; Skin disease; Sensitivity; Association; Susceptibility locus; Systemic disease; Autoimmune disease; Identification; Scleroderma
• ISSN: 1061-4036; 1546-1718; 1546-1718
• DOI: 10.1038/ng.565

Timothy Radstake and Maureen Mayes and colleagues report results of a genome-wide association study of systemic sclerosis. They identify a new susceptibility locus at CD247 . 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.