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Common variants at CD40 and other loci confer risk of rheumatoid arthritis.
|Publication Type||Journal Article|
|Authors||Raychaudhuri, S., Remmers EF, Lee AT, Hackett R., Guiducci C., Burtt NP, Gianniny L., Korman BD, Padyukov L., Kurreeman FA, Chang M., Catanese JJ, Ding B., Wong S., van der Helm-van Mil AH, Neale BM, Coblyn J., Cui J., Tak PP, Wolbink GJ, Crusius JB, van der Horst-Bruinsma IE, Criswell LA, Amos CI, Seldin MF, Kastner DL, Ardlie KG, Alfredsson L., Costenbader KH, Altshuler D., Huizinga TW, Shadick NA, Weinblatt ME, de Vries N., Worthington J., Seielstad M., Toes RE, Karlson EW, Begovich AB, Klareskog L., Gregersen PK, Daly M. J., and Plenge RM|
|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|
|Date Published (YYYY/MM/DD)||2008/10/01|