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- Title
Common variants at CD40 and other loci confer risk of rheumatoid arthritis.
- Authors
Raychaudhuri, Soumya; Remmers, Elaine F.; Lee, Annette T.; Hackett, Rachel; Guiducci, Candace; Burtt, Noël P.; Gianniny, Lauren; Korman, Benjamin D.; Padyukov, Leonid; Kurreeman, Fina A. S.; Chang, Monica; Catanese, Joseph J.; Bo Ding; Wong, Sandra; van der Helm-van Mil, Annette H. M.; Neale, Benjamin M.; Coblyn, Jonathan; Jing Cui; Tak, Paul P.; Wolbink, Gert Jan
- 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 × 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 × 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 × 10−7 overall), CDK6 (rs42041, P = 0.010 replication, P = 4.0 × 10−6 overall), PRKCQ (rs4750316, P = 0.0078 replication, P = 4.4 × 10−6 overall), and KIF5A-PIP4K2C (rs1678542, P = 0.0026 replication, P = 8.8 × 10−8 overall).
- Subjects
RHEUMATOID arthritis; AUTOIMMUNE diseases; CD antigens; AUTOANTIBODIES; AUTOIMMUNITY; META-analysis
- Publication
Nature Genetics, 2008, Vol 40, Issue 10, p1216
- ISSN
1061-4036
- Publication type
Article
- DOI
10.1038/ng.233