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PMID: 20383147 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Nature genetics ·Vol. 42 ·No. 5 ·2010-05-00 ·Pages 426-9

Radstake TR, Gorlova O, Rueda B, Martin JE, Alizadeh BZ, Palomino-Morales R, Coenen MJ, Vonk MC, Voskuyl AE, Schuerwegh AJ, Broen JC, van Riel PL, van 't Slot R, Italiaander A, Ophoff RA, Riemekasten G, Hunzelmann N, Simeon CP, Ortego-Centeno N, González-Gay MA, González-Escribano MF, Spanish Scleroderma Group, Airo P, van Laar J, Herrick A, Worthington J, Hesselstrand R, Smith V, de Keyser F, Houssiau F, Chee MM, Madhok R, Shiels P, Westhovens R, Kreuter A, Kiener H, de Baere E, Witte T, Padykov L, Klareskog L, Beretta L, Scorza R, Lie BA, Hoffmann-Vold AM, Carreira P, Varga J, Hinchcliff M, Gregersen PK, Lee AT, Ying J, Han Y, Weng SF, Amos CI, Wigley FM, Hummers L, Nelson JL, Agarwal SK, Assassi S, Gourh P, Tan FK, Koeleman BP, Arnett FC, Martin J, Mayes MD

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.

MeSH Terms
Adult Aged CD3 Complex/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
Chemicals
CD3 Complex CD3 antigen, zeta chain
Authors & Affiliations
64 authors, click to expand affiliations / ORCID
Radstake Timothy R D J
Department of Rheumatology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands. [email protected]
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
Spanish Scleroderma Group
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
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Article Info
Journal
Nature genetics
Abbr.
Nat Genet
ISSN
1546-1718
DOI
10.1038/ng.565
Email
[email protected]
Published
2010-05-00
Epub
2010-00-11
Pages
426-9
Language
English
Region
United States
NLM ID
9216904
PMCID
PMC2861917
Subset
IM
Grants
NIMH NIH HHS · R01 MH078075 · United States
NIAMS NIH HHS · R01 AR055258-02 · United States
NIAMS NIH HHS · P50 AR054144 · United States
NIAID NIH HHS · R01 AI041721-12 · United States
NIAMS NIH HHS · K08AR054404 · United States
NIAMS NIH HHS · K08 AR054404-02 · United States
NCRR NIH HHS · UL1 RR024148 · United States
NIAMS NIH HHS · K08 AR054404 · United States
NCRR NIH HHS · 3UL1RR024148 · United States
NIMH NIH HHS · R01 MH078075-04 · United States
NIAMS NIH HHS · P50AR054144 · United States
NIAMS NIH HHS · R01 AR055258 · United States
NIAMS NIH HHS · N01-AR-02251 · United States
NIAMS NIH HHS · P50 AR054144-04 · United States
NCRR NIH HHS · UL1 RR024148-02 · United States
Arthritis Research UK · 17552 · United Kingdom
NIAID NIH HHS · R01 AI041721 · United States
NIAMS NIH HHS · N01 AR002251-013 · United States
External Links
PubMed source DOI: 10.1038/ng.565 PMC Full Text View journal details
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