REL, encoding a member of the NF-kappaB family of transcription factors, is a newly defined risk locus for rheumatoid arthritis.
We conducted a genome-wide association study of rheumatoid arthritis in 2,418 cases and 4,504 controls from North America and identified an association at the REL locus, encoding c-Rel, on chromosome 2p13 (rs13031237, P = 6.01 x 10(-10)). Replication in independent case-control datasets comprising 2,604 cases and 2,882 controls confirmed this association, yielding an allelic OR = 1.25 (P = 3.08 x 10(-14)) for marker rs13031237 and an allelic OR = 1.21 (P = 2.60 x 10(-11)) for marker rs13017599 in the combined dataset. The combined dataset also provides definitive support for associations at both CTLA4 (rs231735; OR = 0.85; P = 6.25 x 10(-9)) and BLK (rs2736340; OR = 1.19; P = 5.69 x 10(-9)). c-Rel is an NF-kappaB family member with distinct functional properties in hematopoietic cells, and its association with rheumatoid arthritis suggests disease pathways that involve other recently identified rheumatoid arthritis susceptibility genes including CD40, TRAF1, TNFAIP3 and PRKCQ.
Gregersen
Peter K
PK
The Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, NY, USA.
Amos
Chistopher I
CI
Lee
Annette T
AT
Lu
Yue
Y
Remmers
Elaine F
EF
Kastner
Daniel L
DL
Seldin
Michael F
MF
Criswell
Lindsey A
LA
Plenge
Robert M
RM
Holers
V Michael
VM
Mikuls
Ted R
TR
Sokka
Tuulikki
T
Moreland
Larry W
LW
Bridges
S Louis
SL
Xie
Gang
G
Begovich
Ann B
AB
Siminovitch
Katherine A
KA
D001172:Arthritis, Rheumatoid / Q000235:genetics*; D020573:Genes, rel; D055106:Genome-Wide Association Study; D006801:Humans; D020641:Polymorphism, Single Nucleotide