Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants
by Wellcome Trust Case Control Consortium, Burton Paul R, Clayton David G, Cardon Lon R, Craddock Nick, Deloukas Panos, Duncanson Audrey, Kwiatkowski Dominic P, McCarthy Mark I, Ouwehand Willem H, Samani Nilesh J, Todd John A, Donnelly Chair Peter, Analysis Committee:, Barrett Jeffrey C, Davison Dan, Donnelly Peter, Easton Doug, Evans David M, Leung Hin-Tak, Marchini Jonathan L, Morris Andrew P, Spencer Chris Ca, Tobin Martin D, UK Blood Services & University of Cambridge Controls:, Attwood Antony P, Boorman James P, Cant Barbara, Everson Ursula, Hussey Judith M, Jolley Jennifer D, Knight Alexandra S, Koch Kerstin, Meech Elizabeth, Nutland Sarah, Prowse Christopher V, Stevens Helen E, Taylor Niall C, Walters Graham R, Walker Neil M, Watkins Nicholas A, Winzer Thilo, 1958 Birth Cohort Controls:, Jones Richard W, McArdle Wendy L, Ring Susan M, Strachan David P, Pembrey Marcus, Bipolar Disorder (Aberdeen):, Breen Gerome, Clair David St, (Birmingham):, Caesar Sian, Gordon-Smith Katharine, Jones Lisa, (Cardiff):, Fraser Christine, Green Elaine K, Grozeva Detelina, Hamshere Marian L, Holmans Peter A, Jones Ian R, Kirov George, Moskivina Valentina, Nikolov Ivan, O'Donovan Michael C, Owen Michael J, (London):, Collier David A, Elkin Amanda, Farmer Anne, Williamson Richard, McGuffin Peter, (Newcastle):, Young Allan H, Ferrier I Nicol, Coronary Artery Disease (Leeds):, Ball Stephen G, Balmforth Anthony J, Barrett Jennifer H, Bishop Timothy D, Iles Mark M, Maqbool Azhar, Yuldasheva Nadira, Hall Alistair S, (Leicester):, Braund Peter S, Dixon Richard J, Mangino Massimo, Stevens Suzanne, Thompson John R, Crohn's Disease (Cambridge):, Bredin Francesca, Tremelling Mark, Parkes Miles, (Edinburgh):, Drummond Hazel, Lees Charles W, Nimmo Elaine R, Satsangi Jack, Fisher Sheila A, Forbes Alastair, Lewis Cathryn M, Onnie Clive M, Prescott Natalie J, Sanderson Jeremy, Matthew Christopher G, Barbour Jamie, Mohiuddin M Khalid, Todhunter Catherine E, Mansfield John C, (Oxford):, Ahmad Tariq, Cummings Fraser R, Jewell Derek P, Hypertension (Aberdeen):, Webster John, (Cambridge):, Brown Morris J, (Evry, France):, Lathrop Mark G, (Glasgow):, Connell John, Dominiczak Anna, Marcano Carolina A Braga, Burke Beverley, Dobson Richard, Gungadoo Johannie, Lee Kate L, Munroe Patricia B, Newhouse Stephen J, Onipinla Abiodun, Wallace Chris, Xue Mingzhan, Caulfield Mark, Farrall Martin, Rheumatoid Arthritis:, Barton Anne, The Biologics in RA Genetics and Genomics Study Syndicate (BRAGGS) Steering Committee*,, Bruce Ian N, Donovan Hannah, Eyre Steve, Gilbert Paul D, Hilder Samantha L, Hinks Anne M, John Sally L, Potter Catherine, Silman Alan J, Symmons Deborah Pm, Thomson Wendy, Worthington Jane, Type 1 Diabetes:, Dunger David B, Widmer Barry, Type 2 Diabetes (Exeter):, Frayling Timothy M, Freathy Rachel M, Lango Hana, Perry John R B, Shields Beverley M, Weedon Michael N, Hattersley Andrew T, Hitman Graham A, Walker Mark, Elliott Kate S, Groves Christopher J, Lindgren Cecilia M, Rayner Nigel W, Timpson Nicolas J, Zeggini Eleftheria, Tuberculosis (Gambia):, Newport Melanie, Sirugo Giorgio, Lyons Emily, Vannberg Fredrik, Hill Adrian V S, Ankylosing Spondylitis:, Bradbury Linda A, Farrar Claire, Pointon Jennifer J, Wordsworth Paul, Brown Matthew A, Autoimmune Thyroid Disease:, Franklyn Jayne A, Heward Joanne M, Simmonds Matthew J, Gough Stephen Cl, Breast Cancer:, Seal Sheila, Breast Cancer Susceptibility Collaboration (UK)*,, Stratton Michael R, Rahman Nazneen, Multiple Sclerosis:, Ban Maria, Goris An, Sawcer Stephen J, Compston Alastair, Gambian Controls (Gambia):, Conway David, Jallow Muminatou, Rockett Kirk A, DNA, Genotyping, Data QC and Informatics (Wellcome Trust Sanger Institute, Hinxton):, Bumpstead Suzannah J, Chaney Amy, Downes Kate, Ghori Mohammed Jr, Gwilliam Rhian, Hunt Sarah E, Inouye Michael, Keniry Andrew, King Emma, McGinnis Ralph, Potter Simon, Ravindrarajah Rathi, Whittaker Pamela, Widden Claire, Withers David, Statistics (Cambridge):, Cardin Niall J, Ferreira Teresa, Pereira-Gale Joanne, Hallgrimsdóttir Ingeleif B, Howie Bryan N, Su Zhan, Teo Yik Ying, Vukcevic Damjan, Principal Investigators:, Bentley David, AITD Replication Group:, Mitchell Sarah L, Newby Paul R, Brand Oliver J, Carr-Smith Jackie, Pearce Simon H S, Gough Stephen C L, IL23R replication:, McGinnis R, Keniry A, Deloukas P, The Australo-Anglo-American Spondylitis Consortium (TASC), Reveille John D, Zhou Xiaodong, Sims Anne-Marie, Dowling Alison, Taylor Jacqueline, Doan Tracy, Davis John C, Savage Laurie, Ward Michael M, Learch Thomas L, Weisman Michael H in Nat Genet (2007).
PMID: 17952073

Relationships

Gene/Drug/Disease Relationship
TSHR, Autoimmune Thyroid Disease
IL23R, Inflammatory Bowel Diseases
FCRL3, Autoimmune Thyroid Disease, Graves Disease
IL7R, Multiple Sclerosis
IL23R, Spondylitis, Ankylosing
FCRL5, Graves Disease
PIK3R2, Multiple Sclerosis
PCGF2, Breast Neoplasms
C8B, IL7R, TYK2, Autoimmune Thyroid Disease
CR1, LNPEP, SIGLEC1, Spondylitis, Ankylosing

Categories of Pharmacogenetic Knowledge?

CO    Clinical Outcome
GN    Genotype

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.

Keywords

ARTS1, HLA-B27, genome-wide association study, nonsynomyous SNP, rs11209032, rs2287987, rs230318, rs27044, rs30187, rs3761959, rs3783941

Publication Type

  • Human Study
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