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. 2010 May;42(5):426-9.
doi: 10.1038/ng.565. Epub 2010 Apr 11.

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

Timothy R D J Radstake  1 , Olga Gorlova, Blanca Rueda, Jose-Ezequiel Martin, Behrooz Z Alizadeh, Rogelio Palomino-Morales, Marieke J Coenen, Madelon C Vonk, Alexandre E Voskuyl, Annemie J Schuerwegh, Jasper C Broen, Piet L C M van Riel, Ruben van 't Slot, Annet Italiaander, Roel A Ophoff, Gabriela Riemekasten, Nico Hunzelmann, Carmen P Simeon, Norberto Ortego-Centeno, Miguel A González-Gay, María F González-Escribano; Spanish Scleroderma Group; Paolo Airo, Jaap van Laar, Ariane Herrick, Jane Worthington, Roger Hesselstrand, Vanessa Smith, Filip de Keyser, Fredric Houssiau, Meng May Chee, Rajan Madhok, Paul Shiels, Rene Westhovens, Alexander Kreuter, Hans Kiener, Elfride de Baere, Torsten Witte, Leonid Padykov, Lars Klareskog, Lorenzo Beretta, Rafaella Scorza, Benedicte A Lie, Anna-Maria Hoffmann-Vold, Patricia Carreira, John Varga, Monique Hinchcliff, Peter K Gregersen, Annette T Lee, Jun Ying, Younghun Han, Shih-Feng Weng, Christopher I Amos, Fredrick M Wigley, Laura Hummers, J Lee Nelson, Sandeep K Agarwal, Shervin Assassi, Pravitt Gourh, Filemon K Tan, Bobby P C Koeleman, Frank C Arnett, Javier Martin, Maureen D Mayes
Affiliations

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

Timothy R D J Radstake et al. Nat Genet. 2010 May.

Abstract

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 x 10(-7) in the discovery samples, P = 3.39 x 10(-9) in the combined analysis). Additionally, we confirm and firmly establish the role of the MHC (P = 2.31 x 10(-18)), IRF5 (P = 1.86 x 10(-13)) and STAT4 (P = 3.37 x 10(-9)) gene regions as SSc genetic risk factors.

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Figures

Figure 1
Figure 1
Manhattan plot of the Genome wide association study of the discovery cohort comprising 2346 SSc patients and 5193 healthy controls. The –log10 of the Mantel-Haenszel test P value of 279.621 SNPs after correction by λ is plotted against its physical chromosomal position. Chromosomes are showed in alternate colors. SNPs above the red line represent those with a P-value of 5 < 10−7. Plot corresponds to the combined analysis of the study cohorts.
Figure 2
Figure 2
Forest plot showing the odds ratios and confidence intervals of the CD247 association in the various populations studied both in the discovery and replication cohorts.
See this image and copyright information in PMC

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