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

Paul R. Burton, David G. Clayton, Lon R. Cardon, Nick Craddock, Panos Deloukas, Audrey Duncanson, Dominic P. Kwiatkowski, Mark I. McCarthy, Willem H. Ouwehand, Nilesh J. Samani, John A. Todd, Peter Donnelly, Jeffrey C. Barrett, Dan Davison, Doug Easton, David M. Evans, Hin Tak Leung, Jonathan L. Marchini, Andrew P. Morris, Chris C.A. SpencerMartin D. Tobin, Antony P. Attwood, James P. Boorman, Barbara Cant, Ursula Everson, Judith M. Hussey, Jennifer D. Jolley, Alexandra S. Knight, Kerstin Koch, Elizabeth Meech, Sarah Nutland, Christopher V. Prowse, Helen E. Stevens, Niall C. Taylor, Graham R. Walters, Neil M. Walker, Nicholas A. Watkins, Thilo Winzer, Richard W. Jones, Wendy L. McArdle, Susan M. Ring, David P. Strachan, Marcus Pembrey, Gerome Breen, David St Clair, Sian Caesar, Katharine Gordon-Smith, Lisa Jones, Christine Fraser, Elaine K. Green, Detelina Grozeva, Marian L. Hamshere, Peter A. Holmans, Ian R. Jones, George Kirov, Valentina Moskivina, Ivan Nikolov, Michael C. O'Donovan, Michael J. Owen, David A. Collier, Amanda Elkin, Anne Farmer, Richard Williamson, Peter McGuffin, Allan H. Young, I. Nicol Ferrier, Stephen G. Ball, Anthony J. Balmforth, Jennifer H. Barrett, Timothy D. Bishop, Mark M. Iles, Azhar Maqbool, Nadira Yuldasheva, Alistair S. Hall, Peter S. Braund, Richard J. Dixon, Massimo Mangino, Suzanne Stevens, John R. Thompson, Francesca Bredin, Mark Tremelling, Miles Parkes, Hazel Drummond, Charles W. Lees, Elaine R. Nimmo, Jack Satsangi, Sheila A. Fisher, Alastair Forbes, Cathryn M. Lewis, Clive M. Onnie, Natalie J. Prescott, Jeremy Sanderson, Christopher G. Matthew, Jamie Barbour, M. Khalid Mohiuddin, Catherine E. Todhunter, John C. Mansfield, Tariq Ahmad, Fraser R. Cummings, Derek P. Jewell, John Webster, Morris J. Brown, Mark G. Lathrop, John Connell, Anna Dominiczak, Carolina A.Braga Marcano, Beverley Burke, Richard Dobson, Johannie Gungadoo, Kate L. Lee, Patricia B. Munroe, Stephen J. Newhouse, Abiodun Onipinla, Chris Wallace, Mingzhan Xue, Mark Caulfield, 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, David B. Dunger, Barry Widmer, Timothy M. Frayling, Rachel M. Freathy, Hana Lango, John R.B. Perry, Beverley M. Shields, Michael N. Weedon, Andrew T. Hattersley, Graham A. Hitman, Mark Walker, Kate S. Elliott, Christopher J. Groves, Cecilia M. Lindgren, Nigel W. Rayner, Nicolas J. Timpson, Eleftheria Zeggini, 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, 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, Niall J. Cardin, Teresa Ferreira, Joanne Pereira-Gale, Ingeleif B. Hallgrimsdóttir, Bryan N. Howie, Zhan Su, Yik Ying Teo, Damjan Vukcevic, David Bentley, Sarah L. Mitchell, Paul R. Newby, Oliver J. Brand, Jackie Carr-Smith, Simon H.S. Pearce, Stephen C.L. Gough, R. McGinnis, A. Keniry, John D. Reveille, Xiaodong Zhou, Anne Marie Sims, Alison Dowling, Jacqueline Taylor, Tracy Doan, John C. Davis, Laurie Savage, Michael M. Ward, Thomas L. Learch, Michael H. Weisman

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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.

Original languageEnglish
Pages (from-to)1329-1337
Number of pages9
JournalNature Genetics
Volume39
Issue number11
DOIs
StatePublished - 1 Nov 2007
Externally publishedYes

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