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Letter

Nature Genetics 39, 1477–1482 (1 December 2007) | doi:10.1038/ng.2007.27

Two independent alleles at 6q23 associated with risk of rheumatoid arthritis

Robert M Plenge , Chris Cotsapas , Leela Davies , Alkes L Price , Paul I W de Bakker , Julian Maller , Itsik Pe'er , Noel P Burtt , Brendan Blumenstiel , Matt DeFelice , Melissa Parkin , Rachel Barry , Wendy Winslow , Claire Healy , Robert R Graham , Benjamin M Neale , Elena Izmailova , Ronenn Roubenoff , Alexander N Parker , Roberta Glass , Elizabeth W Karlson , Nancy Maher , David A Hafler , David M Lee , Michael F Seldin , Elaine F Remmers , Annette T Lee , Leonid Padyukov , Lars Alfredsson , Jonathan Coblyn , Michael E Weinblatt , Stacey B Gabriel , Shaun Purcell , Lars Klareskog , Peter K Gregersen , Nancy A Shadick , Mark J Daly & David Altshuler

To identify susceptibility alleles associated with rheumatoid arthritis, we genotyped 397 individuals with rheumatoid arthritis for 116,204 SNPs and carried out an association analysis in comparison to publicly available genotype data for 1,211 related individuals from the Framingham Heart Study. After evaluating and adjusting for technical and population biases, we identified a SNP at 6q23 (rs10499194, |[sim]|150 kb from TNFAIP3 and OLIG3) that was reproducibly associated with rheumatoid arthritis both in the genome-wide association (GWA) scan and in 5,541 additional case-control samples (P = 10|[minus]|3, GWA scan; P |[minus]|6, replication; P = 10|[minus]|9, combined).