Two independent alleles at 6q23 associated with risk of rheumatoid arthritis by Plenge Robert M, Cotsapas Chris, Davies Leela, Price Alkes L, de Bakker Paul I W, Maller Julian, Pe'er Itsik, Burtt Noel P, Blumenstiel Brendan, DeFelice Matt, Parkin Melissa, Barry Rachel, Winslow Wendy, Healy Claire, Graham Robert R, Neale Benjamin M, Izmailova Elena, Roubenoff Ronenn, Parker Alexander N, Glass Roberta, Karlson Elizabeth W, Maher Nancy, Hafler David A, Lee David M, Seldin Michael F, Remmers Elaine F, Lee Annette T, Padyukov Leonid, Alfredsson Lars, Coblyn Jonathan, Weinblatt Michael E, Gabriel Stacey B, Purcell Shaun, Klareskog Lars, Gregersen Peter K, Shadick Nancy A, Daly Mark J, Altshuler David in Nature genetics (2007).

[PMID: 17982456] PubMed


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, approximately 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(-3), GWA scan; P < 10(-6), replication; P = 10(-9), combined). In a concurrent study, the Wellcome Trust Case Control Consortium (WTCCC) has reported strong association of rheumatoid arthritis susceptibility to a different SNP located 3.8 kb from rs10499194 (rs6920220; P = 5 x 10(-6) in WTCCC). We show that these two SNP associations are statistically independent, are each reproducible in the comparison of our data and WTCCC data, and define risk and protective haplotypes for rheumatoid arthritis at 6q23.

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