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

Nat Genet. 2010 Jun;42(6):508-14. Epub 2010 May 09
Eli A Stahl 1 , Soumya Raychaudhuri , Elaine F Remmers , Gang Xie , Stephen Eyre , Brian P Thomson , Yonghong Li , Fina A S Kurreeman , Alexandra Zhernakova , Anne Hinks , Candace Guiducci , Robert Chen , Lars Alfredsson , Christopher I Amos , Kristin G Ardlie , BIRAC Consortium , Anne Barton , John Bowes , Elisabeth Brouwer , Noel P Burtt , Joseph J Catanese , Jonathan Coblyn , Marieke J H Coenen , Karen H Costenbader , Lindsey A Criswell , J Bart A Crusius , Jing Cui , Paul I W de Bakker , Philip L De Jager , Bo Ding , Paul Emery , Edward Flynn , Pille Harrison , Lynne J Hocking , Tom W J Huizinga , Daniel L Kastner , Xiayi Ke , Annette T Lee , Xiangdong Liu , Paul Martin , Ann W Morgan , Leonid Padyukov , Marcel D Posthumus , Timothy R D J Radstake , David M Reid , Mark Seielstad , Michael F Seldin , Nancy A Shadick , Sophia Steer , Paul P Tak , Wendy Thomson , Annette H M van der Helm-van Mil , Irene E van der Horst-Bruinsma , C Ellen van der Schoot , Piet L C M van Riel , Michael E Weinblatt , Anthony G Wilson , Gert Jan Wolbink , B Paul Wordsworth , YEAR Consortium , Cisca Wijmenga , Elizabeth W Karlson , Rene E M Toes , Niek de Vries , Ann B Begovich , Jane Worthington , Katherine A Siminovitch , Peter K Gregersen , Lars Klareskog , Robert M Plenge
Eli A Stahl 1 , Soumya Raychaudhuri , Elaine F Remmers , Gang Xie , Stephen Eyre , Brian P Thomson , Yonghong Li , Fina A S Kurreeman , Alexandra Zhernakova , Anne Hinks , Candace Guiducci , Robert Chen , Lars Alfredsson , Christopher I Amos , Kristin G Ardlie , BIRAC Consortium , Anne Barton , John Bowes , Elisabeth Brouwer , Noel P Burtt , Joseph J Catanese , Jonathan Coblyn , Marieke J H Coenen , Karen H Costenbader , Lindsey A Criswell , J Bart A Crusius , Jing Cui , Paul I W de Bakker , Philip L De Jager , Bo Ding , Paul Emery , Edward Flynn , Pille Harrison , Lynne J Hocking , Tom W J Huizinga , Daniel L Kastner , Xiayi Ke , Annette T Lee , Xiangdong Liu , Paul Martin , Ann W Morgan , Leonid Padyukov , Marcel D Posthumus , Timothy R D J Radstake , David M Reid , Mark Seielstad , Michael F Seldin , Nancy A Shadick , Sophia Steer , Paul P Tak , Wendy Thomson , Annette H M van der Helm-van Mil , Irene E van der Horst-Bruinsma , C Ellen van der Schoot , Piet L C M van Riel , Michael E Weinblatt , Anthony G Wilson , Gert Jan Wolbink , B Paul Wordsworth , YEAR Consortium , Cisca Wijmenga , Elizabeth W Karlson , Rene E M Toes , Niek de Vries , Ann B Begovich , Jane Worthington , Katherine A Siminovitch , Peter K Gregersen , Lars Klareskog , Robert M Plenge
+ et al

[No authors listed]

Author information
  • 1 Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, Massachusetts, USA.

摘要

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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