Common variants at CD40 and other loci confer risk of rheumatoid arthritis.

Nat Genet
Authors
Keywords
Abstract

To identify rheumatoid arthritis risk loci in European populations, we conducted a meta-analysis of two published genome-wide association (GWA) studies totaling 3,393 cases and 12,462 controls. We genotyped 31 top-ranked SNPs not previously associated with rheumatoid arthritis in an independent replication of 3,929 autoantibody-positive rheumatoid arthritis cases and 5,807 matched controls from eight separate collections. We identified a common variant at the CD40 gene locus (rs4810485, P = 0.0032 replication, P = 8.2 x 10(-9) overall, OR = 0.87). Along with other associations near TRAF1 (refs. 2,3) and TNFAIP3 (refs. 4,5), this implies a central role for the CD40 signaling pathway in rheumatoid arthritis pathogenesis. We also identified association at the CCL21 gene locus (rs2812378, P = 0.00097 replication, P = 2.8 x 10(-7) overall), a gene involved in lymphocyte trafficking. Finally, we identified evidence of association at four additional gene loci: MMEL1-TNFRSF14 (rs3890745, P = 0.0035 replication, P = 1.1 x 10(-7) overall), CDK6 (rs42041, P = 0.010 replication, P = 4.0 x 10(-6) overall), PRKCQ (rs4750316, P = 0.0078 replication, P = 4.4 x 10(-6) overall), and KIF5A-PIP4K2C (rs1678542, P = 0.0026 replication, P = 8.8 x 10(-8) overall).

Year of Publication
2008
Journal
Nat Genet
Volume
40
Issue
10
Pages
1216-23
Date Published
2008 Oct
ISSN
1546-1718
URL
DOI
10.1038/ng.233
PubMed ID
18794853
PubMed Central ID
PMC2757650
Links
Grant list
R01 AR044422-10 / AR / NIAMS NIH HHS / United States
M01 RR000079 / RR / NCRR NIH HHS / United States
R01-AR44422 / AR / NIAMS NIH HHS / United States
5 M01 RR-00079 / RR / NCRR NIH HHS / United States
K24 AR0524-01 / AR / NIAMS NIH HHS / United States
P01 CA087969 / CA / NCI NIH HHS / United States
R01 AR044422 / AR / NIAMS NIH HHS / United States
U01 HG004171 / HG / NHGRI NIH HHS / United States
CA87969 / CA / NCI NIH HHS / United States
K08 AR055688-01A1 / AR / NIAMS NIH HHS / United States
17552 / Arthritis Research UK / United Kingdom
R01 AI065841 / AI / NIAID NIH HHS / United States
K08 KAR055688A / PHS HHS / United States
P60 AR047782 / AR / NIAMS NIH HHS / United States
T32 AR007530 / AR / NIAMS NIH HHS / United States
R01 AR49880 / AR / NIAMS NIH HHS / United States
K24 AR02175 / AR / NIAMS NIH HHS / United States
R01 AR049880 / AR / NIAMS NIH HHS / United States
Arthritis Research UK / United Kingdom
UO1 HG004171 / HG / NHGRI NIH HHS / United States
N01-AR-2-2263 / AR / NIAMS NIH HHS / United States
Z01 AR041139-05 / Intramural NIH HHS / United States
AR007530-23 / AR / NIAMS NIH HHS / United States
K08 AR055688 / AR / NIAMS NIH HHS / United States
K12 HD051959 / HD / NICHD NIH HHS / United States
K24 AR002175 / AR / NIAMS NIH HHS / United States
K08 AI055314 / AI / NIAID NIH HHS / United States
R01 AR044422-09A1 / AR / NIAMS NIH HHS / United States
U54 RR020278 / RR / NCRR NIH HHS / United States
K08 AI55314-3 / AI / NIAID NIH HHS / United States