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Nat Genet. 2012 Dec;44(12):1336-40. doi: 10.1038/ng.2462. Epub 2012 Nov 11.

High-density genetic mapping identifies new susceptibility loci for rheumatoid arthritis.

Collaborators (412)

Barton A, Isaacs J, Morgan A, Wilson G, Hyrich K, Moitra RK, Prouse PJ, Shawe DJ, Crisp AJ, Gaston JS, Hall FC, Hazleman BL, Jenner JR, Lillicrap MS, Ostor A, Silverman B, Speed C, Bruce IN, Hyrich K, Ho P, Gorodkin R, Armstrong D, Chuck AJ, Hailwood S, Kumar N, Badcock LJ, Deighton CM, O'Reilly SC, Raj N, Regan MR, Summers GD, Williams RA, Lambert JR, Stevens R, Wilkinson C, Hamilton J, Heycock CR, Kelly CA, Saravanan V, Rees DH, Williams RB, Bingham S, Emery P, Morgan A, Bird HA, Conaghan PG, Pease CT, Wakefield RJ, Chalam SV, Mulherin D, Price T, Sheeran T, Venkatachalam S, Gaffney K, Macgregor AJ, Marshall T, Merry P, Scott DG, Birrell FN, Crook PR, Harrison B, Pattrick M, Snowden HN, Bowden AP, Smith EE, Klimiuk P, Speden DJ, Sheehan NJ, Williams NE, Dahiya S, Hull RG, Ledingham JM, Mccrae F, Shaban MR, Thomas AL, Young Min SA, Bamji AN, Cheung NT, Buckley CD, Carruthers DC, Elamanchi R, Gordon PC, Grindulis KA, Khattak F, Raza K, Situnayake D, Till S, Akil M, Tattersall R, Kilding R, Dunley L, Boulton J, Tait T, Wilson AG, Bax DE, Clarke F, Fordham JN, Plant MJ, Tuck, Pathare SK, Edwards CJ, Arden NK, Armstrong RD, Calogeras A, Cooper C, Davidson BK, Dennison EM, Abernethy VE, Clewes AR, Dawson JK, Lynch M, Kitas G, Delamere JP, Erb N, Klocke R, Whallett AJ, Crook P, Foster HE, Griffiths B, Griffiths ID, Grove ML, Isaacs JD, Kay L, Ng WF, Myers A, Platt PN, Walker DJ, Bowman, Jobanputra P, Jubb RW, Rankin EC, Dawes PT, Dowson CM, Hassell A, Hay EM, Kamath S, Packham J, Sandhu RS, Shadforth MF, Bukhari M, Dodds WN, Halsey JP, Mitchell WS, O'Reilly DT, Donnelly SP, Doyle D, Hakim A, Lanham JG, Tahir HI, Rathi J, Rai A, Rowe IF, Prabu A, Buckley CA, Burton PR, Clayton DG, Cardon LR, Craddock N, Deloukas P, Duncanson A, Kwiatkowski DP, McCarthy MI, Ouwehand WH, Samani NJ, Todd JA, Donnelly P, Barrett JC, Burton PR, Davison D, Donnelly P, Easton D, Evans D, Leung HT, Marchini JL, Morris AP, Spencer CC, Tobin MD, Cardon LR, Clayton DG, Attwood AP, Boorman JP, Cant B, Everson U, Hussey JM, Jolley JD, Knight AS, Koch K, Meech E, Nutland S, Prowse CV, Stevens HE, Taylor NC, Walters GR, Walker NM, Watkins NA, Winzer T, Todd JA, Ouwehand WH, Jones RW, McArdle WL, Ring SM, Strachan DP, Pembrey M, Breen G, St Clair D, Caesar S, Gordon-Smith K, Jones L, Fraser C, Green EK, Grozeva D, Hamshere ML, Holmans PA, Jones IR, Kirov G, Moskvina V, Nikolov I, O'Donovan MC, Owen MJ, Craddock N, Collier DA, Elkin A, Farmer A, Williamson R, McGuffin P, Young AH, Ferrier IN, Ball SG, Balmforth AJ, Barrett JH, Bishop DT, Iles MM, Maqbool A, Yuldasheva N, Hall AS, Braund PS, Burton PR, Dixon RJ, Mangino M, Stevens S, Tobin MD, Thompson JR, Samani NJ, Bredin F, Tremelling M, Parkes M, Drummond H, Lees CW, Nimmo ER, Satsangi J, Fisher SA, Forbes A, Lewis CM, Onnie CM, Prescott NJ, Sanderson J, Mathew CG, Barbour J, Mohiuddin MK, Todhunter CE, Mansfield JC, Ahmad T, Cummings FR, Jewell DP, Webster J, Brown MJ, Clayton DG, Lathrop GM, Connell J, Dominiczak A, Samani NJ, Braga Marcano CA, Burke B, Dobson R, Gungadoo J, Lee KL, Munroe PB, Newhouse SJ, Onipinla A, Wallace C, Xue M, Caulfield M, Farrall M, Barton A, Bruce IN, Donovan H, Eyre S, Gilbert PD, Hider SL, Hinks AM, John SL, Potter C, Silman AJ, Symmons DP, Thomson W, Worthington J, Clayton DG, Dunger DB, Nutland S, Stevens HE, Walker NM, Widmer B, Todd JA, Frayling TM, Freathy RM, Lango H, Perry JR, Shields BM, Weedon MN, Hattersley AT, Hitman GA, Walker M, Elliott KS, Groves CJ, Lindgren CM, Rayner NW, Timpson NJ, Zeggini E, McCarthy MI, Newport M, Sirugo G, Lyons E, Vannberg F, Hill AV, Bradbury LA, Farrar C, Pointon JJ, Wordsworth P, Brown MA, Franklyn JA, Heward JM, Simmonds MJ, Gough SC, Seal S, Stratton MR, Rahman N, Ban M, Goris A, Sawcer SJ, Compston A, Conway D, Jallow M, Newport M, Sirugo G, Rockett KA, Kwiatkowski DP, Bumpstead SJ, Chaney A, Downes K, Ghori MJ, Gwilliam R, Hunt SE, Inouye M, Keniry A, King E, McGinnis R, Potter S, Ravindrarajah R, Whittaker P, Widden C, Withers D, Deloukas P, Leung HT, Nutland S, Stevens HE, Walker NM, Todd JA, Easton D, Clayton DG, Burton PR, Tobin MD, Barrett JC, Evans D, Morris AP, Cardon LR, Cardin NJ, Davison D, Ferreira T, Pereira-Gale J, Hallgrimsdóttir IB, Howie BN, Marchini JL, Spencer CC, Su Z, Teo YY, Vukcevic D, Donnelly P, Bentley D, Brown MA, Cardon LR, Caulfield M, Clayton DG, Compston A, Craddock N, Deloukas P, Donnelly P, Farrall M, Gough SC, Hall AS, Hattersley AT, Hill AV, Kwiatkowski DP, Mathew CG, McCarthy MI, Ouwehand WH, Parkes M, Pembrey M, Rahman N, Samani NJ, Stratton MR, Todd JA, Worthington J.

Abstract

Using the Immunochip custom SNP array, which was designed for dense genotyping of 186 loci identified through genome-wide association studies (GWAS), we analyzed 11,475 individuals with rheumatoid arthritis (cases) of European ancestry and 15,870 controls for 129,464 markers. We combined these data in a meta-analysis with GWAS data from additional independent cases (n = 2,363) and controls (n = 17,872). We identified 14 new susceptibility loci, 9 of which were associated with rheumatoid arthritis overall and five of which were specifically associated with disease that was positive for anticitrullinated peptide antibodies, bringing the number of confirmed rheumatoid arthritis risk loci in individuals of European ancestry to 46. We refined the peak of association to a single gene for 19 loci, identified secondary independent effects at 6 loci and identified association to low-frequency variants at 4 loci. Bioinformatic analyses generated strong hypotheses for the causal SNP at seven loci. This study illustrates the advantages of dense SNP mapping analysis to inform subsequent functional investigations.

PMID:
23143596
PMCID:
PMC3605761
DOI:
10.1038/ng.2462
[PubMed - indexed for MEDLINE]
Free PMC Article

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