TY - JOUR
T1 - Common variants at CD40 and other loci confer risk of rheumatoid arthritis
AU - Raychaudhuri, Soumya
AU - Remmers, Elaine F.
AU - Lee, Annette T.
AU - Hackett, Rachel
AU - Guiducci, Candace
AU - Burtt, Noël P.
AU - Gianniny, Lauren
AU - Korman, Benjamin D.
AU - Padyukov, Leonid
AU - Kurreeman, Fina A S
AU - Chang, Monica
AU - Catanese, Joseph J.
AU - Ding, Bo
AU - Wong, Sandra
AU - Van Der Helm-Van Mil, Annette H M
AU - Neale, Benjamin M.
AU - Coblyn, Jonathan
AU - Cui, Jing
AU - Tak, Paul P.
AU - Wolbink, Gert Jan
AU - Crusius, J. Bart A
AU - Horst-Bruinsma, Irene E Van Der
AU - Criswell, Lindsey A.
AU - Amos, Christopher I.
AU - Seldin, Michael F
AU - Kastner, Daniel L.
AU - Ardlie, Kristin G.
AU - Alfredsson, Lars
AU - Costenbader, Karen H.
AU - Altshuler, David
AU - Huizinga, Tom W J
AU - Shadick, Nancy A.
AU - Weinblatt, Michael E.
AU - De Vries, Niek
AU - Worthington, Jane
AU - Seielstad, Mark
AU - Toes, Rene E M
AU - Karlson, Elizabeth W.
AU - Begovich, Ann B.
AU - Klareskog, Lars
AU - Gregersen, Peter K.
AU - Daly, Mark J.
AU - Plenge, Robert M.
PY - 2008/10
Y1 - 2008/10
N2 - 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).
AB - 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).
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U2 - 10.1038/ng.233
DO - 10.1038/ng.233
M3 - Article
C2 - 18794853
AN - SCOPUS:52949111858
VL - 40
SP - 1216
EP - 1223
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 10
ER -