Genome-wide association study of systemic sclerosis identifies CD247 as a new susceptibility locus.
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.
Radstake
Timothy R D J
TR
Department of Rheumatology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands. tradstake73@gmail.com
Gorlova
Olga
O
Rueda
Blanca
B
Martin
Jose-Ezequiel
JE
Alizadeh
Behrooz Z
BZ
Palomino-Morales
Rogelio
R
Coenen
Marieke J
MJ
Vonk
Madelon C
MC
Voskuyl
Alexandre E
AE
Schuerwegh
Annemie J
AJ
Broen
Jasper C
JC
van Riel
Piet L C M
PL
van 't Slot
Ruben
R
Italiaander
Annet
A
Ophoff
Roel A
RA
Riemekasten
Gabriela
G
Hunzelmann
Nico
N
Simeon
Carmen P
CP
Ortego-Centeno
Norberto
N
González-Gay
Miguel A
MA
González-Escribano
María F
MF
Airo
Paolo
P
van Laar
Jaap
J
Herrick
Ariane
A
Worthington
Jane
J
Hesselstrand
Roger
R
Smith
Vanessa
V
de Keyser
Filip
F
Houssiau
Fredric
F
Chee
Meng May
MM
Madhok
Rajan
R
Shiels
Paul
P
Westhovens
Rene
R
Kreuter
Alexander
A
Kiener
Hans
H
de Baere
Elfride
E
Witte
Torsten
T
Padykov
Leonid
L
Klareskog
Lars
L
Beretta
Lorenzo
L
Scorza
Rafaella
R
Lie
Benedicte A
BA
Hoffmann-Vold
Anna-Maria
AM
Carreira
Patricia
P
Varga
John
J
Hinchcliff
Monique
M
Gregersen
Peter K
PK
Lee
Annette T
AT
Ying
Jun
J
Han
Younghun
Y
Weng
Shih-Feng
SF
Amos
Christopher I
CI
Wigley
Fredrick M
FM
Hummers
Laura
L
Nelson
J Lee
JL
Agarwal
Sandeep K
SK
Assassi
Shervin
S
Gourh
Pravitt
P
Tan
Filemon K
FK
Koeleman
Bobby P C
BP
Arnett
Frank C
FC
Martin
Javier
J
Mayes
Maureen D
MD
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*
D017252:CD3 Complex; C121704:CD3 antigen, zeta chain
Ann Rheum Dis. 2010 May;69(5):822-7
19596691
Mol Immunol. 2004 Apr;40(18):1295-305
15072848
Blood. 2001 Jun 15;97(12):3851-9
11389026
Nat Genet. 2007 Jul;39(7):870-4
17529973
Arthritis Rheum. 2009 Jun;60(6):1845-50
19479858
Rheum Dis Clin North Am. 2008 Feb;34(1):17-40; v
18329530
Community Genet. 2006;9(1):55-61
16490960
Nature. 2007 Jun 7;447(7145):661-78
17554300
J Immunol. 2003 Apr 15;170(8):4189-95
12682251
Hum Mol Genet. 2009 Jun 1;18(11):2071-7
19286670
Arthritis Rheum. 2009 Jan;60(1):225-33
19116937
Nat Genet. 2007 May;39(5):645-9
17401363
Ann Rheum Dis. 2009 Aug;68(8):1375-6
19605749
Arthritis Rheum. 2006 Dec;54(12):3945-53
17133608
Am J Hum Genet. 2007 Sep;81(3):559-75
17701901
Ann Intern Med. 2004 Jan 6;140(1):37-50
14706971
J Immunol. 2008 Jan 15;180(2):1060-70
18178846
Tissue Antigens. 2009 Jul;74(1):68-72
19422667
N Engl J Med. 2009 May 7;360(19):1989-2003
19420368
Arthritis Rheum. 1980 May;23(5):581-90
7378088
Annu Rev Immunol. 2009;27:363-91
19302045
Nature. 2008 Sep 11;455(7210):232-6
18668039
Mol Med. 2009 Nov-Dec;15(11-12):371-83
19707526
J Immunol. 2005 Sep 1;175(5):3417-23
16116236