Genome-wide association study of systemic sclerosis identifies CD247 as a novel 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., Scheurwegh, 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, R, Shiels, Paul, Westhovens, Rene, Kreuter, Alexander, Kiener, Hans, de Baere, Elfride, Witte, Torsten, Padykov, Leonid, Klareskog, Lars, Beretta, Lorenzo, Scorza, Rafaella, Lie, Benedicte A., Hoffman-Vold, Anna-Maria, Carreira, P, Varga, J., Hinchcliff, M., Gregersen, Peter, 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: 11.04.2010
• ISSN: 1061-4036; 1546-1718
• DOI: 10.1038/ng.565

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 novel SSc susceptibility loci we conducted the first genome wide association study (GWAS) in a population of Caucasian ancestry including a total of 2296 SSc patients and 5171 controls. Analysis of 279,621 autosomal single nucleotide polymorphisms (SNPs) followed by replication testing in an independent case-control set of European ancestry (2,753 SSc patients / 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 MHC (2.31 × 10 −18 ), IRF5 (P =1.86 × 10 −13 ) and STAT4 (P =3.37 × 10 −9 ) gene regions as SSc genetic risk factors.