Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci.
Stahl EA., Raychaudhuri S., Remmers EF., Xie G., Eyre S., Thomson BP., Li Y., Kurreeman FAS., Zhernakova A., Hinks A., Guiducci C., Chen R., Alfredsson L., Amos CI., Ardlie KG., BIRAC Consortium None., Barton A., Bowes J., Brouwer E., Burtt NP., Catanese JJ., Coblyn J., Coenen MJH., Costenbader KH., Criswell LA., Crusius JBA., Cui J., de Bakker PIW., De Jager PL., Ding B., Emery P., Flynn E., Harrison P., Hocking LJ., Huizinga TWJ., Kastner DL., Ke X., Lee AT., Liu X., Martin P., Morgan AW., Padyukov L., Posthumus MD., Radstake TRDJ., Reid DM., Seielstad M., Seldin MF., Shadick NA., Steer S., Tak PP., Thomson W., van der Helm-van Mil AHM., van der Horst-Bruinsma IE., van der Schoot CE., van Riel PLCM., Weinblatt ME., Wilson AG., Wolbink GJ., Wordsworth BP., YEAR Consortium None., Wijmenga C., Karlson EW., Toes REM., de Vries N., Begovich AB., Worthington J., Siminovitch KA., Gregersen PK., Klareskog L., Plenge RM.
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.