title: Genome-wide association study of systemic sclerosis identifies CD247 as a new susceptibility locus.
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.
authors.affiliation: Department of Rheumatology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands. tradstake73@gmail.com
authors.forename: Timothy R D J
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authors.lastname: Radstake
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authors.lastname: Kiener
authors.forename: Elfride
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authors.lastname: de Baere
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authors.lastname: Klareskog
authors.forename: Lorenzo
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authors.lastname: Beretta
authors.forename: Rafaella
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authors.lastname: Lie
authors.forename: Anna-Maria
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authors.lastname: Hoffmann-Vold
authors.forename: Patricia
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authors.lastname: Carreira
authors.forename: John
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authors.lastname: Varga
authors.forename: Monique
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authors.lastname: Hinchcliff
authors.forename: Peter K
authors.initials: PK
authors.lastname: Gregersen
authors.forename: Annette T
authors.initials: AT
authors.lastname: Lee
authors.forename: Jun
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authors.lastname: Ying
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authors.lastname: Han
authors.forename: Shih-Feng
authors.initials: SF
authors.lastname: Weng
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authors.initials: CI
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authors.forename: Fredrick M
authors.initials: FM
authors.lastname: Wigley
authors.forename: Laura
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authors.lastname: Hummers
authors.forename: J Lee
authors.initials: JL
authors.lastname: Nelson
authors.forename: Sandeep K
authors.initials: SK
authors.lastname: Agarwal
authors.forename: Shervin
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authors.lastname: Assassi
authors.forename: Pravitt
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authors.lastname: Gourh
authors.forename: Filemon K
authors.initials: FK
authors.lastname: Tan
authors.forename: Bobby P C
authors.initials: BP
authors.lastname: Koeleman
authors.forename: Frank C
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mesh_terms: D000328:Adult; D000368:Aged; D017252:CD3 Complex / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D005060:Europe; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D012307:Risk Factors; D012595:Scleroderma, Systemic / Q000235:genetics*
chemical_list: D017252:CD3 Complex; C121704:CD3 antigen, zeta chain
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