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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 MJ Plenge RM 《Nature genetics》2008,40(10):1216-1223
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). 相似文献
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