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

Soumya Raychaudhuri, Elaine F. Remmers, Annette T. Lee, Rachel Hackett, Candace Guiducci, Noël P. Burtt, Lauren Gianniny, Benjamin D. Korman, Leonid Padyukov, Fina A S Kurreeman, Monica Chang, Joseph J. Catanese, Bo Ding, Sandra Wong, Annette H M Van Der Helm-Van Mil, Benjamin M. Neale, Jonathan Coblyn, Jing Cui, Paul P. Tak, Gert Jan WolbinkJ. Bart A Crusius, Irene E Van Der Horst-Bruinsma, Lindsey A. Criswell, Christopher I. Amos, Michael F Seldin, Daniel L. Kastner, Kristin G. Ardlie, Lars Alfredsson, Karen H. Costenbader, David Altshuler, Tom W J Huizinga, Nancy A. Shadick, Michael E. Weinblatt, Niek De Vries, Jane Worthington, Mark Seielstad, Rene E M Toes, Elizabeth W. Karlson, Ann B. Begovich, Lars Klareskog, Peter K. Gregersen, Mark J. Daly, Robert M. Plenge

Research output: Contribution to journalArticle

400 Scopus citations

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).

Original languageEnglish (US)
Pages (from-to)1216-1223
Number of pages8
JournalNature Genetics
Volume40
Issue number10
DOIs
StatePublished - Oct 2008

ASJC Scopus subject areas

  • Genetics

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    Raychaudhuri, S., Remmers, E. F., Lee, A. T., Hackett, R., Guiducci, C., Burtt, N. P., Gianniny, L., Korman, B. D., Padyukov, L., Kurreeman, F. A. S., Chang, M., Catanese, J. J., Ding, B., Wong, S., Van Der Helm-Van Mil, A. H. M., Neale, B. M., Coblyn, J., Cui, J., Tak, P. P., ... Plenge, R. M. (2008). Common variants at CD40 and other loci confer risk of rheumatoid arthritis. Nature Genetics, 40(10), 1216-1223. https://doi.org/10.1038/ng.233