Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants
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 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 DM., Morris AP., Cardon LR., Cardin NJ., Davison D., Ferreira T., Pereira-Gale J., Hallgrimsdottir 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 AVS., Kwiatkowski DP., Matthew CG., McCarthy MI., Ouwehand WH., Parkes M., Pembrey M., Rahman N., Samani NJ., Stratton MR., Todd JA., Worthington J., Mitchell SL., Newby PR., Brand OJ., Carr-Smith J., Pearce SHS., Gough SCL., McGinnis R.
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.