Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants

Melanie Newport, Giorgio Sirugo, Emily Lyons, Fredrik Vannberg, Adrian V. S. Hill, Linda A. Bradbury, Claire Farrar, Jennifer J. Pointon, Paul Wordsworth, Matthew A. Brown, Jayne A. Franklyn, Joanne M. Heward, Matthew J. Simmonds, Stephen C. L. Gough, Sheila Seal, Michael R. Stratton, Nazneen Rahman, Maria Ban, An Goris, Stephen J. Sawcer, Alastair Compston, David Conway, Muminatou Jallow, Kirk A. Rockett, Dominic P. Kwiatkowski, Suzannah J. Bumpstead, Amy Chaney, Kate Downes, Mohammed J. R. Ghori, Rhian Gwilliam, Sarah E. Hunt, Michael Inouye, Andrew Keniry, Emma King, Ralph McGinnis, Simon Potter, Rathi Ravindrarajah, Pamela Whittaker, Claire Widden, David Withers, Panos Deloukas, Hin-Tak Leung, Sarah Nutland, Helen E. Stevens, Neil M. Walker, John A. Todd, Doug Easton, David G. Clayton, Paul R. Burton, Martin D. Tobin, Jeffrey C. Barrett, David M. Evans, Andrew P. Morris, Lon R. Cardon, Niall J. Cardin, Dan Davison, Teresa Ferreira, Joanne Pereira-Gale, Ingeleif B. Hallgrimsdottir, Bryan N. Howie, Jonathan L. Marchini, Chris C. A. Spencer, Zhan Su, Yik Ying Teo, Damjan Vukcevic, Peter Donnelly, David Bentley, Mark Caulfield, Nick Craddock, Martin Farrall, Anne Barton, Ian N. Bruce, Hannah Donovan, Steve Eyre, Paul D. Gilbert, Samantha L. Hilder, Anne M. Hinks, Sally L. John, Catherine Potter, Alan J. Silman, Deborah P. M. Symmons, Wendy Thomson, Jane Worthington, Alistair S. Hall, Andrew T. Hattersley, Christopher G. Matthew, Mark I. McCarthy, Willem H. Ouwehand, Miles Parkes, Marcus Pembrey, Nilesh J. Samani, Sarah L. Mitchell, Paul R. Newby, Oliver J. Brand, Jackie Carr-Smith, Simon H. S. Pearce, R. McGinnis, A. Keniry, P. Deloukas, John D. Reveille, others

Nature Genetics 01/2007; 39:1329-1337.

ABSTRACT 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.

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