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Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci

Authors :
Robert M. Plenge
Elisabeth Brouwer
Cisca Wijmenga
Christopher I. Amos
Anthony G. Wilson
Noël P. Burtt
Stephen Eyre
Paul P. Tak
Pille Harrison
Daniel L. Kastner
Robert Chen
Gang Xie
Gertjan Wolbink
Bo Ding
Niek de Vries
B. Paul Wordsworth
Paul I.W. de Bakker
David M. Reid
Xiangdong Liu
Mark Seielstad
Tom W J Huizinga
Lynne J. Hocking
Peter K. Gregersen
Leonid Padyukov
Jing Cui
Annette Lee
Sophia Steer
J. Bart A. Crusius
C. Ellen van der Schoot
Yonghong Li
Philip L. De Jager
Michael F. Seldin
Kristin G. Ardlie
Anne Barton
Marieke J H Coenen
Annette H M van der Helm-van Mil
Nancy A. Shadick
Ann W. Morgan
Fina A S Kurreeman
Katherine A. Siminovitch
Elaine F. Remmers
Timothy R D J Radstake
René E. M. Toes
Anne Hinks
Jane Worthington
Karen H. Costenbader
Joseph J. Catanese
Elizabeth W. Karlson
Alexandra Zhernakova
Edward Flynn
Xiayi Ke
Brian Thomson
Soumya Raychaudhuri
Jonathan S. Coblyn
Lars Alfredsson
Marcel D. Posthumus
John Bowes
Irene E. van der Horst-Bruinsma
Ann B. Begovich
Wendy Thomson
Paul Martin
Candace Guiducci
Piet L. C. M. van Riel
Paul Emery
Michael E. Weinblatt
Lars Klareskog
Lindsey A. Criswell
Eli A. Stahl
Rheumatology
CCA - Disease profiling
Pathology
Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI)
Translational Immunology Groningen (TRIGR)
AII - Amsterdam institute for Infection and Immunity
Clinical Immunology and Rheumatology
Landsteiner Laboratory
Clinical Haematology
Source :
Stahl, E A, Raychaudhuri, S, Remmers, E F, Xie, G, Eyre, S, Thomson, B P, Li, Y H, Kurreeman, F A S, Zhernakova, A, Hinks, A, Guiducci, C, Chen, R, Alfredsson, L, Amos, C I, Ardlie, K G, Barton, A, Bowes, J, Brouwer, E, Burtt, N P, Catanese, J J, Coblyn, J, Coenen, M J H, Costenbader, K H, Criswell, L A, Crusius, J B A, Cui, J, Bakker, P I W, de Jager, P L, Ding, B, Emery, P, Flynn, E, Harrison, P, Hocking, L J, Huizinga, T W J, Kastner, D L, Ke, X Y, Lee, A T, Liu, X D, Martin, P, Morgan, A W, Padyukov, L, Posthumus, M D, Radstake, T R D J, Reid, D M, Seielstad, M, Seldin, M F, Shadick, N A, Steer, S, Tak, P P, Thomson, W, van der Helm-va Mil, A, van der Horst-Bruinsma, I E, van der Schoot, C E, van Riel, P L C M, Weinblatt, M E, Wilson, A G, Wolbink, G J J, Wordsworth, B P, Wijmenga, C, Karlson, E W, Toes, R E M, de Vries, N, Begovich, A B, Worthington, J, Siminovitch, K A, Gregersen, P K, Klareskog, L & Plenge, R M 2010, ' Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci ', Nature Genetics, vol. 42, no. 6, pp. 508-514 . https://doi.org/10.1038/ng.582, Nature Genetics, 42, 508-14, Nature Genetics, 42(6), 508-514. Nature Publishing Group, Nature Genetics, 42(6), 508-U56. Nature Publishing Group, Nature Genetics, 42, 6, pp. 508-14, Nature genetics, 42(6), 508-U56. Nature Publishing Group, Nature Genetics, 42(6), 508
Publication Year :
2010

Abstract

Contains fulltext : 88498.pdf (Publisher’s version ) (Closed access) 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. 01 juni 2010

Details

Language :
English
ISSN :
15461718 and 10614036
Volume :
42
Issue :
6
Database :
OpenAIRE
Journal :
Nature genetics
Accession number :
edsair.doi.dedup.....b61dda1ae57d1d63bce515394af10052