| High-density genetic mapping identifies new susceptibility loci for rheumatoid arthritis. | |
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MedLine Citation:
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PMID: 23143596 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Using the Immunochip custom SNP array, which was designed for dense genotyping of 186 loci identified through genome-wide association studies (GWAS), we analyzed 11,475 individuals with rheumatoid arthritis (cases) of European ancestry and 15,870 controls for 129,464 markers. We combined these data in a meta-analysis with GWAS data from additional independent cases (n = 2,363) and controls (n = 17,872). We identified 14 new susceptibility loci, 9 of which were associated with rheumatoid arthritis overall and five of which were specifically associated with disease that was positive for anticitrullinated peptide antibodies, bringing the number of confirmed rheumatoid arthritis risk loci in individuals of European ancestry to 46. We refined the peak of association to a single gene for 19 loci, identified secondary independent effects at 6 loci and identified association to low-frequency variants at 4 loci. Bioinformatic analyses generated strong hypotheses for the causal SNP at seven loci. This study illustrates the advantages of dense SNP mapping analysis to inform subsequent functional investigations. |
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Authors:
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Steve Eyre; John Bowes; Dorothée Diogo; Annette Lee; Anne Barton; Paul Martin; Alexandra Zhernakova; Eli Stahl; Sebastien Viatte; Kate McAllister; Christopher I Amos; Leonid Padyukov; Rene E M Toes; Tom W J Huizinga; Cisca Wijmenga; Gosia Trynka; Lude Franke; Harm-Jan Westra; Lars Alfredsson; Xinli Hu; Cynthia Sandor; Paul I W de Bakker; Sonia Davila; Chiea Chuen Khor; Khai Koon Heng; Robert Andrews; Sarah Edkins; Sarah E Hunt; Cordelia Langford; Deborah Symmons; ; ; Pat Concannon; Suna Onengut-Gumuscu; Stephen S Rich; Panos Deloukas; Miguel A Gonzalez-Gay; Luis Rodriguez-Rodriguez; Lisbeth Ärlsetig; Javier Martin; Solbritt Rantapää-Dahlqvist; Robert M Plenge; Soumya Raychaudhuri; Lars Klareskog; Peter K Gregersen; Jane Worthington |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2012-11-11 |
Journal Detail:
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Title: Nature genetics Volume: 44 ISSN: 1546-1718 ISO Abbreviation: Nat. Genet. Publication Date: 2012 Dec |
Date Detail:
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Created Date: 2012-11-29 Completed Date: 2013-02-13 Revised Date: 2013-05-17 |
Medline Journal Info:
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Nlm Unique ID: 9216904 Medline TA: Nat Genet Country: United States |
Other Details:
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Languages: eng Pagination: 1336-40 Citation Subset: IM |
Affiliation:
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Arthritis Research UK Epidemiology Unit, Centre for Musculoskeletal Research, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Arthritis, Rheumatoid
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genetics* Autoantibodies / blood, genetics Chromosome Mapping / instrumentation, methods* European Continental Ancestry Group / genetics Female Genetic Loci* Genetic Predisposition to Disease* Genome-Wide Association Study Humans Male Oligonucleotide Array Sequence Analysis Polymorphism, Single Nucleotide |
| Grant Support | |
ID/Acronym/Agency:
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068545/Z/02//Wellcome Trust; 076113/C/04/Z//Wellcome Trust; 091157//Wellcome Trust; 17552//Arthritis Research UK; 1R01AR062886-01/AR/NIAMS NIH HHS; G0000934//Medical Research Council; K08AR055688/AR/NIAMS NIH HHS; MC_U147585819//Medical Research Council; MC_UP_A620_1014//Medical Research Council; N01-AR-2-2263/AR/NIAMS NIH HHS; N01-AR1-2256/AR/NIAMS NIH HHS; R01 AI068759/AI/NIAID NIH HHS; R01 AR062886/AR/NIAMS NIH HHS; R01-AR-4-4422/AR/NIAMS NIH HHS; R01-AR056768/AR/NIAMS NIH HHS; R01-AR057108/AR/NIAMS NIH HHS; R01-AR059648/AR/NIAMS NIH HHS; RC2AR059092-01/AR/NIAMS NIH HHS; U01-GM092691/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Autoantibodies |
| Investigator | |
Investigator/Affiliation:
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Anne Barton / ; John Isaacs / ; Ann Morgan / ; Gerry Wilson / ; Kimme Hyrich / ; R K Moitra / ; P J Prouse / ; D J Shawe / ; A J Crisp / ; J S H Gaston / ; F C Hall / ; B L Hazleman / ; J R Jenner / ; M S Lillicrap / ; A Ostor / ; B Silverman / ; C Speed / ; I N Bruce / ; K Hyrich / ; P Ho / ; R Gorodkin / ; D Armstrong / ; A J Chuck / ; S Hailwood / ; N Kumar / ; L J Badcock / ; C M Deighton / ; S C O'Reilly / ; N Raj / ; M R Regan / ; G D Summers / ; R A Williams / ; J R Lambert / ; R Stevens / ; C Wilkinson / ; J Hamilton / ; C R Heycock / ; C A Kelly / ; V Saravanan / ; D H Rees / ; R B Williams / ; S Bingham / ; P Emery / ; A Morgan / ; H A Bird / ; P G Conaghan / ; C T Pease / ; R J Wakefield / ; S V Chalam / ; D Mulherin / ; T Price / ; T Sheeran / ; S Venkatachalam / ; K Gaffney / ; A J Macgregor / ; T Marshall / ; P Merry / ; D G I Scott / ; F N Birrell / ; P R Crook / ; B Harrison / ; M Pattrick / ; H N Snowden / ; A P Bowden / ; E E Smith / ; P Klimiuk / ; D J Speden / ; N J Sheehan / ; N E Williams / ; S Dahiya / ; R G Hull / ; J M Ledingham / ; F Mccrae / ; M R Shaban / ; A L Thomas / ; S A Young Min / ; A N Bamji / ; N T Cheung / ; C D Buckley / ; D C Carruthers / ; R Elamanchi / ; P C Gordon / ; K A Grindulis / ; F Khattak / ; K Raza / ; D Situnayake / ; S Till / ; M Akil / ; R Tattersall / ; R Kilding / ; L Dunley / ; J Boulton / ; T Tait / ; A G Wilson / ; D E Bax / ; F Clarke / ; J N Fordham / ; M J Plant / ; Tuck / ; S K Pathare / ; C J Edwards / ; N K Arden / ; R D Armstrong / ; A Calogeras / ; C Cooper / ; B K S Davidson / ; E M Dennison / ; V E Abernethy / ; A R Clewes / ; J K Dawson / ; M Lynch / ; G Kitas / ; J P Delamere / ; N Erb / ; R Klocke / ; A J Whallett / ; P Crook / ; H E Foster / ; B Griffiths / ; I D Griffiths / ; M L Grove / ; J D Isaacs / ; L Kay / ; W F Ng / ; A Myers / ; P N Platt / ; D J Walker / ; Bowman / ; P Jobanputra / ; R W Jubb / ; E C Rankin / ; P T Dawes / ; C M Dowson / ; A Hassell / ; E M Hay / ; S Kamath / ; J Packham / ; R S Sandhu / ; M F Shadforth / ; M Bukhari / ; W N Dodds / ; J P Halsey / ; W S Mitchell / ; D T O'Reilly / ; S P Donnelly / ; D Doyle / ; A Hakim / ; J G Lanham / ; H I S Tahir / ; J Rathi / ; A Rai / ; I F Rowe / ; A Prabu / ; C A M Buckley / ; 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 / ; Paul R Burton / ; Dan Davison / ; Peter Donnelly / ; Doug Easton / ; David Evans / ; Hin-Tak Leung / ; Jonathan L Marchini / ; Andrew P Morris / ; Chris C A Spencer / ; Martin D Tobin / ; Lon R Cardon / ; David G Clayton / ; 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 / ; John A Todd / ; Willem H Ouwehand / ; Richard W Jones / ; Wendy L McArdle / ; Susan M Ring / ; David P Strachan / ; Marcus Pembrey / ; Gerome Breen / ; David St Clair / ; Sian Caesar / ; Katherine Gordon-Smith / ; Lisa Jones / ; Christine Fraser / ; Elaine K Green / ; Detelina Grozeva / ; Marian L Hamshere / ; Peter A Holmans / ; Ian R Jones / ; George Kirov / ; Valentina Moskvina / ; Ivan Nikolov / ; Michael C O'Donovan / ; Michael J Owen / ; Nick Craddock / ; 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 / ; D Timothy Bishop / ; Mark M Iles / ; Azhar Maqbool / ; Nadira Yuldasheva / ; Alistair S Hall / ; Peter S Braund / ; Paul R Burton / ; Richard J Dixon / ; Massimo Mangino / ; Suzanne Stevens / ; Martin D Tobin / ; John R Thompson / ; Nilesh J Samani / ; 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 Mathew / ; Jamie Barbour / ; M Khalid Mohiuddin / ; Catherine E Todhunter / ; John C Mansfield / ; Tariq Ahmad / ; Fraser R Cummings / ; Derek P Jewell / ; John Webster / ; Morris J Brown / ; David G Clayton / ; G Mark Lathrop / ; John Connell / ; Anna Dominiczak / ; Nilesh J Samani / ; 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 Hider / ; Anne M Hinks / ; Sally L John / ; Catherine Potter / ; Alan J Silman / ; Deborah P M Symmons / ; Wendy Thomson / ; Jane Worthington / ; David G Clayton / ; David B Dunger / ; Sarah Nutland / ; Helen E Stevens / ; Neil M Walker / ; Barry Widmer / ; John A Todd / ; 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 / ; Nicholas J Timpson / ; Eleftheria Zeggini / ; Mark I McCarthy / ; 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 / ; Melanie Newport / ; Giorgio Sirugo / ; 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 Evans / ; Andrew P Morris / ; Lon R Cardon / ; Niall J Cardin / ; Dan Davison / ; Teresa Ferreira / ; Joanne Pereira-Gale / ; Ingileif B Hallgrimsdóttir / ; Bryan N Howie / ; Jonathan L Marchini / ; Chris C A Spencer / ; Zhan Su / ; Yik Ying Teo / ; Damjan Vukcevic / ; Peter Donnelly / ; David Bentley / ; Matthew A Brown / ; Lon R Cardon / ; Mark Caulfield / ; David G Clayton / ; Alistair Compston / ; Nick Craddock / ; Panos Deloukas / ; Peter Donnelly / ; Martin Farrall / ; Stephen C L Gough / ; Alistair S Hall / ; Andrew T Hattersley / ; Adrian V S Hill / ; Dominic P Kwiatkowski / ; Christopher G Mathew / ; Mark I McCarthy / ; Willem H Ouwehand / ; Miles Parkes / ; Marcus Pembrey / ; Nazneen Rahman / ; Nilesh J Samani / ; Michael R Stratton / ; John A Todd / ; Jane Worthington / |
| Comments/Corrections | |
Comment In:
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Nat Rev Rheumatol. 2013 Jan;9(1):4
[PMID:
23208187
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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