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Nat Genet. 2009 Dec;41(12):1313-8. doi: 10.1038/ng.479. Epub 2009 Nov 8.

Genetic variants at CD28, PRDM1 and CD2/CD58 are associated with rheumatoid arthritis risk.

Collaborators (141)

Bruce IN, Hyrich K, Ho P, Gorodkin R, Badcock LJ, Deighton CM, O'Reilly SC, Raj N, Regan MR, Summers GD, Williams RA, Barton A, Knight SM, Symmons DP, Sanders P, Pal B, Gaffney K, Macgregor AJ, Marshall T, Merry P, Scott DG, Porter D, Madok R, Gordon M, McInnes I, Sturrock R, Field M, Harrison B, Pattrick M, Snowden HN, Bowden AP, Smith EE, Klimiuk P, Speden DJ, Thompson PW, Richards SC, Hull RG, Ledingham JM, Mccrae F, Shaban MR, Thomas AL, Young Min SA, Herrick AL, Cooper RG, Benitha R, Jones AK, O'Neill TW, Abernethy VE, Clewes AR, Dawson JK, Lynch M, Kitas G, Delamere JP, Erb N, Klocke R, Whallett AJ, Dawes PT, Dowson CM, Hassell A, Hay EM, Kamath S, Packham J, Sandhu RS, Shadforth MF, Bingham S, Emery P, Morgan A, Bird HA, Conaghan PG, Pease CT, Wakefield RJ, Chalam SV, Mulherin D, Price T, Sheeran T, Venkatachalam S, Crook P, Foster HE, Griffiths B, Griffiths ID, Grove ML, Isaacs JD, Kay L, Ng WF, Myers A, Platt PN, Walker DJ, Lim KL, Walsh DA, Carter ND, Holt M, Fawthrop FW, Smith GW, Emery P, Conaghan P, Morgan A, Quinn M, Keenan AM, Hensor E, Gough A, Green M, Reece R, Hordon L, Helliwell P, Melsom R, Doherty S, Adebajo A, Harvey A, Jarrett S, Huson G, Isdale A, Martin M, Karim Z, McGonagle D, Pease C, Cox S, Bejarano V, Nam J, Brown C, Thomas C, Pickles D, Hammond A, Neville B, Fairclough A, Nunns C, Gill A, Green J, Rhys-Evans B, Padwell B, Madden J, Taylor L, Smith S, King H, Firth J, Heard J, Sigsworth L, Corscadden D, Henshaw K, Rashid LH, Martin SG, Robinson JI.

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


To discover new rheumatoid arthritis (RA) risk loci, we systematically examined 370 SNPs from 179 independent loci with P < 0.001 in a published meta-analysis of RA genome-wide association studies (GWAS) of 3,393 cases and 12,462 controls. We used Gene Relationships Across Implicated Loci (GRAIL), a computational method that applies statistical text mining to PubMed abstracts, to score these 179 loci for functional relationships to genes in 16 established RA disease loci. We identified 22 loci with a significant degree of functional connectivity. We genotyped 22 representative SNPs in an independent set of 7,957 cases and 11,958 matched controls. Three were convincingly validated: CD2-CD58 (rs11586238, P = 1 x 10(-6) replication, P = 1 x 10(-9) overall), CD28 (rs1980422, P = 5 x 10(-6) replication, P = 1 x 10(-9) overall) and PRDM1 (rs548234, P = 1 x 10(-5) replication, P = 2 x 10(-8) overall). An additional four were replicated (P < 0.0023): TAGAP (rs394581, P = 0.0002 replication, P = 4 x 10(-7) overall), PTPRC (rs10919563, P = 0.0003 replication, P = 7 x 10(-7) overall), TRAF6-RAG1 (rs540386, P = 0.0008 replication, P = 4 x 10(-6) overall) and FCGR2A (rs12746613, P = 0.0022 replication, P = 2 x 10(-5) overall). Many of these loci are also associated to other immunologic diseases.

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