Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci.
To identify new genetic risk factors for rheumatoid arthritis, we conducted a genome-wide association study meta-analysis of 5,539 autoantibody-positive individuals with rheumatoid arthritis (cases) and 20,169 controls of European descent, followed by replication in an independent set of 6,768 rheumatoid arthritis cases and 8,806 controls. Of 34 SNPs selected for replication, 7 new rheumatoid arthritis risk alleles were identified at genome-wide significance (P < 5 x 10(-8)) in an analysis of all 41,282 samples. The associated SNPs are near genes of known immune function, including IL6ST, SPRED2, RBPJ, CCR6, IRF5 and PXK. We also refined associations at two established rheumatoid arthritis risk loci (IL2RA and CCL21) and confirmed the association at AFF3. These new associations bring the total number of confirmed rheumatoid arthritis risk loci to 31 among individuals of European ancestry. An additional 11 SNPs replicated at P < 0.05, many of which are validated autoimmune risk alleles, suggesting that most represent genuine rheumatoid arthritis risk alleles.
Stahl
Eli A
EA
Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Raychaudhuri
Soumya
S
Remmers
Elaine F
EF
Xie
Gang
G
Eyre
Stephen
S
Thomson
Brian P
BP
Li
Yonghong
Y
Kurreeman
Fina A S
FA
Zhernakova
Alexandra
A
Hinks
Anne
A
Guiducci
Candace
C
Chen
Robert
R
Alfredsson
Lars
L
Amos
Christopher I
CI
Ardlie
Kristin G
KG
Barton
Anne
A
Bowes
John
J
Brouwer
Elisabeth
E
Burtt
Noel P
NP
Catanese
Joseph J
JJ
Coblyn
Jonathan
J
Coenen
Marieke J H
MJ
Costenbader
Karen H
KH
Criswell
Lindsey A
LA
Crusius
J Bart A
JB
Cui
Jing
J
de Bakker
Paul I W
PI
De Jager
Philip L
PL
Ding
Bo
B
Emery
Paul
P
Flynn
Edward
E
Harrison
Pille
P
Hocking
Lynne J
LJ
Huizinga
Tom W J
TW
Kastner
Daniel L
DL
Ke
Xiayi
X
Lee
Annette T
AT
Liu
Xiangdong
X
Martin
Paul
P
Morgan
Ann W
AW
Padyukov
Leonid
L
Posthumus
Marcel D
MD
Radstake
Timothy R D J
TR
Reid
David M
DM
Seielstad
Mark
M
Seldin
Michael F
MF
Shadick
Nancy A
NA
Steer
Sophia
S
Tak
Paul P
PP
Thomson
Wendy
W
van der Helm-van Mil
Annette H M
AH
van der Horst-Bruinsma
Irene E
IE
van der Schoot
C Ellen
CE
van Riel
Piet L C M
PL
Weinblatt
Michael E
ME
Wilson
Anthony G
AG
Wolbink
Gert Jan
GJ
Wordsworth
B Paul
BP
Wijmenga
Cisca
C
Karlson
Elizabeth W
EW
Toes
Rene E M
RE
de Vries
Niek
N
Begovich
Ann B
AB
Worthington
Jane
J
Siminovitch
Katherine A
KA
Gregersen
Peter K
PK
Klareskog
Lars
L
Plenge
Robert M
RM
D001172:Arthritis, Rheumatoid / Q000235:genetics*; D001323:Autoantibodies / Q000008:administration & dosage; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
D001323:Autoantibodies
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