1. Common variants at CD40 and other loci confer risk of rheumatoid arthritis
- Author
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Robert M. Plenge, J. Bart A. Crusius, Niek de Vries, Soumya Raychaudhuri, Mark Seielstad, Tom W J Huizinga, Ann B. Begovich, Lars Klareskog, Peter K. Gregersen, Benjamin D. Korman, René E. M. Toes, Elizabeth W. Karlson, Annette Lee, Lindsey A. Criswell, Monica Chang, Candace Guiducci, Sandra Wong, Nancy A. Shadick, Karen H. Costenbader, Joseph J. Catanese, Michael F. Seldin, David Altshuler, Lauren Gianniny, Daniel L. Kastner, Elaine F. Remmers, Jane Worthington, Paul P. Tak, Annette H M van der Helm-van Mil, Michael E. Weinblatt, Kristin G. Ardlie, Jing Cui, Rachel Hackett, Fina A S Kurreeman, Gertjan Wolbink, Mark J. Daly, Benjamin M. Neale, Bo Ding, Irene E. van der Horst-Bruinsma, Jonathan S. Coblyn, Lars Alfredsson, Christopher I. Amos, Noël P. Burtt, Leonid Padyukov, Rheumatology, CCA - Disease profiling, Pathology, AII - Amsterdam institute for Infection and Immunity, Clinical Immunology and Rheumatology, and Landsteiner Laboratory
- Subjects
PRKCQ ,Genetic Linkage ,Single-nucleotide polymorphism ,Locus (genetics) ,Biology ,TNFAIP3 ,Polymorphism, Single Nucleotide ,Article ,Arthritis, Rheumatoid ,Genetic linkage ,Genetics ,medicine ,Chromosomes, Human ,Humans ,Genetic Predisposition to Disease ,CD40 Antigens ,Gene ,Genome, Human ,Haplotype ,Chromosome Mapping ,medicine.disease ,Haplotypes ,Rheumatoid arthritis ,Case-Control Studies ,Immunology - 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).
- Published
- 2008