Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants.
Wellcome Trust Case Control Consortium None., Australo-Anglo-American Spondylitis Consortium (TASC) None., 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., Davison D., Easton D., Evans DM., Leung H-T., Marchini JL., Morris AP., Spencer CCA., Tobin MD., 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., 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., Moskivina V., Nikolov I., O'Donovan MC., Owen MJ., Collier DA., Elkin A., Farmer A., Williamson R., McGuffin P., Young AH., Ferrier IN., Ball SG., Balmforth AJ., Barrett JH., Bishop TD., Iles MM., Maqbool A., Yuldasheva N., Hall AS., Braund PS., Dixon RJ., Mangino M., Stevens S., Thompson JR., 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., Matthew CG., Barbour J., Mohiuddin MK., Todhunter CE., Mansfield JC., Ahmad T., Cummings FR., Jewell DP., Webster J., Brown MJ., Lathrop MG., Connell J., Dominiczak A., Marcano CAB., Burke B., Dobson R., Gungadoo J., Lee KL., Munroe PB., Newhouse SJ., Onipinla A., Wallace C., Xue M., Caulfield M., Farrall M., Barton A., Biologics in RA Genetics and Genomics Study Syndicate (BRAGGS) Steering Committee None., Bruce IN., Donovan H., Eyre S., Gilbert PD., Hilder SL., Hinks AM., John SL., Potter C., Silman AJ., Symmons DPM., Thomson W., Worthington J., Dunger DB., Widmer B., Frayling TM., Freathy RM., Lango H., Perry JRB., Shields BM., Weedon MN., Hattersley AT., Hitman GA., Walker M., Elliott KS., Groves CJ., Lindgren CM., Rayner NW., Timpson NJ., Zeggini E., Newport M., Sirugo G., Lyons E., Vannberg F., Hill AVS., Bradbury LA., Farrar C., Pointon JJ., Wordsworth P., Brown MA., Franklyn JA., Heward JM., Simmonds MJ., Gough SCL., Seal S., Breast Cancer Susceptibility Collaboration (UK) None., Stratton MR., Rahman N., Ban M., Goris A., Sawcer SJ., Compston A., Conway D., Jallow M., Newport M., Sirugo G., Rockett KA., Bumpstead SJ., Chaney A., Downes K., Ghori MJR., Gwilliam R., Hunt SE., Inouye M., Keniry A., King E., McGinnis R., Potter S., Ravindrarajah R., Whittaker P., Widden C., Withers D., Cardin NJ., Davison D., Ferreira T., Pereira-Gale J., Hallgrimsdo'ttir IB., Howie BN., Su Z., Teo YY., Vukcevic D., Bentley D., Brown MA., Compston A., Farrall M., Hall AS., Hattersley AT., Hill AVS., Parkes M., Pembrey M., Stratton MR., Mitchell SL., Newby PR., Brand OJ., Carr-Smith J., Pearce SHS., McGinnis R., Keniry A., Deloukas P., Reveille JD., Zhou X., Sims A-M., Dowling A., Taylor J., Doan T., Davis JC., Savage L., Ward MM., Learch TL., Weisman MH., Brown M.
We have genotyped 14,436 nonsynonymous SNPs (nsSNPs) and 897 major histocompatibility complex (MHC) tag SNPs from 1,000 independent cases of ankylosing spondylitis (AS), autoimmune thyroid disease (AITD), multiple sclerosis (MS) and breast cancer (BC). Comparing these data against a common control dataset derived from 1,500 randomly selected healthy British individuals, we report initial association and independent replication in a North American sample of two new loci related to ankylosing spondylitis, ARTS1 and IL23R, and confirmation of the previously reported association of AITD with TSHR and FCRL3. These findings, enabled in part by increased statistical power resulting from the expansion of the control reference group to include individuals from the other disease groups, highlight notable new possibilities for autoimmune regulation and suggest that IL23R may be a common susceptibility factor for the major 'seronegative' diseases.