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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2008-10

AUTHORS

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 Wolbink, J 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

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). More... »

PAGES

1216-1223

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ng.233

DOI

http://dx.doi.org/10.1038/ng.233

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1048421356

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/18794853


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