Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci by Stahl Eli A, Raychaudhuri Soumya, Remmers Elaine F, Xie Gang, Eyre Stephen, Thomson Brian P, Li Yonghong, Kurreeman Fina A S, Zhernakova Alexandra, Hinks Anne, Guiducci Candace, Chen Robert, Alfredsson Lars, Amos Christopher I, Ardlie Kristin G, BIRAC Consortium, Barton Anne, Bowes John, Brouwer Elisabeth, Burtt Noel P, Catanese Joseph J, Coblyn Jonathan, Coenen Marieke J H, Costenbader Karen H, Criswell Lindsey A, Crusius J Bart A, Cui Jing, de Bakker Paul I W, De Jager Philip L, Ding Bo, Emery Paul, Flynn Edward, Harrison Pille, Hocking Lynne J, Huizinga Tom W J, Kastner Daniel L, Ke Xiayi, Lee Annette T, Liu Xiangdong, Martin Paul, Morgan Ann W, Padyukov Leonid, Posthumus Marcel D, Radstake Timothy R D J, Reid David M, Seielstad Mark, Seldin Michael F, Shadick Nancy A, Steer Sophia, Tak Paul P, Thomson Wendy, van der Helm-van Mil Annette H M, van der Horst-Bruinsma Irene E, van der Schoot C Ellen, van Riel Piet L C M, Weinblatt Michael E, Wilson Anthony G, Wolbink Gert Jan, Wordsworth B Paul, YEAR Consortium, Wijmenga Cisca, Karlson Elizabeth W, Toes Rene E M, de Vries Niek, Begovich Ann B, Worthington Jane, Siminovitch Katherine A, Gregersen Peter K, Klareskog Lars, Plenge Robert M in Nature genetics (2010). PubMed

Abstract

To identify new genetic risk factors for rheumatoid arthritis, we conducted a genome-wide association study meta-analysis of 5,539 autoantibody-positive individuals with rheumatoid arthritis (cases) and 20,169 controls of European descent, followed by replication in an independent set of 6,768 rheumatoid arthritis cases and 8,806 controls. Of 34 SNPs selected for replication, 7 new rheumatoid arthritis risk alleles were identified at genome-wide significance (P < 5 x 10(-8)) in an analysis of all 41,282 samples. The associated SNPs are near genes of known immune function, including IL6ST, SPRED2, RBPJ, CCR6, IRF5 and PXK. We also refined associations at two established rheumatoid arthritis risk loci (IL2RA and CCL21) and confirmed the association at AFF3. These new associations bring the total number of confirmed rheumatoid arthritis risk loci to 31 among individuals of European ancestry. An additional 11 SNPs replicated at P < 0.05, many of which are validated autoimmune risk alleles, suggesting that most represent genuine rheumatoid arthritis risk alleles.

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