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

Radstake, Timothy R D J and Gorlova, Olga and Rueda, Blanca and Martin, Jose-Ezequiel and Alizadeh, Behrooz Z and Palomino-Morales, Rogelio and Coenen, Marieke J and Vonk, Madelon C and Voskuyl, Alexandre E and Scheurwegh, Annemie J and Broen, Jasper C and van Riel, Piet L C M and van 't Slot, Ruben and Italiaander, Annet and Ophoff, Roel A and Riemekasten, Gabriela and Hunzelmann, Nico and Simeon, Carmen P and Ortego-Centeno, Norberto and González-Gay, Miguel A and González-Escribano, María F and Airo, Paolo and van Laar, Jaap and Herrick, Ariane and Worthington, Jane and Hesselstrand, Roger and Smith, Vanessa and de Keyser, Filip and Houssiau, Fredric and Chee, Meng May and Madhok, Rajan and Shiels, Paul and Westhovens, Rene and Kreuter, Alexander and Kiener, Hans and de Baere, Elfride and Witte, Torsten and Padykov, Leonid and Klareskog, Lars and Beretta, Lorenzo and Scorza, Rafaella and Lie, Benedicte A and Hoffmann-Vold, Anna-Maria and Carreira, Patricia and Varga, John and Hinchcliff, Monique and Gregersen, Peter K and Lee, Annette T and Ying, Jun and Han, Younghun and Weng, Shih-Feng and Amos, Christopher I and Wigley, Fredrick M and Hummers, Laura and Nelson, J Lee and Agarwal, Sandeep K and Assassi, Shervin and Gourh, Pravitt and Tan, Filemon K and Koeleman, Bobby P C and Arnett, Frank C and Martin, Javier and Mayes, Maureen D (2010) Genome-wide association study of systemic sclerosis identifies CD247 as a new susceptibility locus. Nature genetics, 42 (5). pp. 426-429. ISSN 1546-1718

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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.

Item Type:	Article or Abstract
Additional Information:	This article is available to subscribers only via the URL above.
DOI:	10.1038/ng.565
PubMed ID:	20383147
NIHMSID:	NIHMS196766
PMCID:	PMC2861917
Grant Numbers:	R01 AI041721-12, R01 MH078075-04, N01 AR002251-013, R01 AR055258-02, P50 AR054144-04, UL1 RR024148-02, K08 AR054404-02
Keywords or MeSH Headings:	Adult Aged Antigens, CD3/genetics* Case-Control Studies Cohort Studies Europe Female Genetic Predisposition to Disease* Genome-Wide Association Study* Humans Male Middle Aged Odds Ratio Risk Factors Scleroderma, Systemic/genetics*
Subjects:	Cellular and Organismal Processes > Genetic processes > Mutation Diseases > Autoimmune Research Methodologies > Epidemiology > Risk assessment
Depositing User:	Library Staff
Date Deposited:	16 Apr 2010 18:35
Last Modified:	14 Feb 2012 14:43
URI:	http://authors.fhcrc.org/id/eprint/432

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