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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
High-density genetic mapping identifies new susceptibility loci for rheumatoid arthritis
Nature Genetics, Volume 44, No. 12, Year 2012
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Description
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. © 2012 Nature America, Inc. All rights reserved.
Authors & Co-Authors
Eyre, Stephen
United Kingdom, Manchester
Health Innovation Manchester
United Kingdom, Royston
National Institute for Health and Care Research
United Kingdom, Manchester
The University of Manchester
Bowes, John D.
United Kingdom, Manchester
Health Innovation Manchester
United Kingdom, Royston
National Institute for Health and Care Research
Lee, Annette T.
United States, New York
Northwell Health System
Barton, Anne C.
United Kingdom, Manchester
Health Innovation Manchester
United Kingdom, Royston
National Institute for Health and Care Research
United Kingdom, Manchester
The University of Manchester
Zhernakova, Alexandra
Netherlands, Leiden
Leids Universitair Medisch Centrum
Netherlands, Groningen
Rijksuniversiteit Groningen
Stahl, Eli Ayumi
United States, Boston
Brigham and Women's Hospital
United States, Cambridge
Broad Institute
Viatte, Sebastien
United Kingdom, Manchester
Health Innovation Manchester
United Kingdom, Royston
National Institute for Health and Care Research
Amos, Christopher Ian
United States, Houston
The University of Texas Md Anderson Cancer Center
Padyukov, Leonid
Sweden, Stockholm
Karolinska Institutet
Toes, René E.M.
Netherlands, Leiden
Leids Universitair Medisch Centrum
Huizinga, Tom W.J.
Netherlands, Leiden
Leids Universitair Medisch Centrum
Wijmenga, Cisca
Netherlands, Groningen
Rijksuniversiteit Groningen
Trynka, Gosia
United States, Boston
Brigham and Women's Hospital
United States, Cambridge
Broad Institute
Netherlands, Groningen
Rijksuniversiteit Groningen
Franke, Lude L.
Netherlands, Groningen
Rijksuniversiteit Groningen
Westra, Harm Jan
Netherlands, Groningen
Rijksuniversiteit Groningen
Alfredsson, Lars S.
Sweden, Stockholm
Karolinska Institutet
De Bakker, Paul IW W.
United States, Boston
Brigham and Women's Hospital
United States, Cambridge
Broad Institute
Netherlands, Utrecht
University Medical Center Utrecht
Dávila, Sonia
Singapore, Singapore City
A-star, Genome Institute of Singapore
Khor, Chiea Chuen
Singapore, Singapore City
A-star, Genome Institute of Singapore
Andrews, Robert M.
United Kingdom, Hinxton
Wellcome Sanger Institute
Edkins, Sarah J.
United Kingdom, Hinxton
Wellcome Sanger Institute
Hunt, Sarah E.
United Kingdom, Hinxton
Wellcome Sanger Institute
Langford, Cordelia F.
United Kingdom, Hinxton
Wellcome Sanger Institute
Symmons, Deborah P. M.
United Kingdom, Manchester
Health Innovation Manchester
United Kingdom, Royston
National Institute for Health and Care Research
United Kingdom, Manchester
The University of Manchester
Concannon, Patrick J.
United States, Charlottesville
University of Virginia
Önengüt-Gümüşcü, Suna
United States, Charlottesville
University of Virginia
Rich, Stephen S.
United States, Charlottesville
University of Virginia
Deloukas, Panos
United Kingdom, Hinxton
Wellcome Sanger Institute
United Kingdom, London
Wellcome Trust
González-Gay, Miguel Ángel
Spain, Santander
Hospital Universitario Marqués de Valdecilla
Rodríguez-Rodríguez, Luís Pablo
Spain, Madrid
Hospital Clínico San Carlos
Martin, Javier
Spain, Madrid
Consejo Superior de Investigaciones Científicas
Rantapåå-Dahlqvist, Solbritt
Sweden, Umea
Umeå Universitet
Plenge, Robert M.
United States, Boston
Brigham and Women's Hospital
United States, Cambridge
Broad Institute
Raychaudhuri, Soumya
United Kingdom, Manchester
Health Innovation Manchester
United Kingdom, Royston
National Institute for Health and Care Research
United States, Boston
Brigham and Women's Hospital
United States, Cambridge
Broad Institute
Klareskog, Lars G.
Sweden, Stockholm
Karolinska Institutet
Gregersen, Peter K.
United States, New York
Northwell Health System
Gaston, John Stanley Hill
United Kingdom, Cambridge
Cambridge University Hospitals Nhs Foundation Trust
Hall, Frances C.
United Kingdom, Cambridge
Cambridge University Hospitals Nhs Foundation Trust
Hazleman, Brian Leslie
United Kingdom, Cambridge
Cambridge University Hospitals Nhs Foundation Trust
Ostor, Andrew J.K.
United Kingdom, Cambridge
Cambridge University Hospitals Nhs Foundation Trust
Bruce, Ian N.
United Kingdom, Manchester
Manchester University Nhs Foundation Trust
United Kingdom, Manchester
The University of Manchester
Regan, Marian R.
United Kingdom, Derby
University Hospitals of Derby and Burton Nhs Foundation Trust
Kelly, Clive Anthony
United Kingdom, Tyne and Wear
Gateshead Health Nhs Foundation Trust
Saravanan, Vadivelu
United Kingdom, Tyne and Wear
Gateshead Health Nhs Foundation Trust
Bingham, Sheila Anne
United Kingdom, Leeds
Leeds Teaching Hospitals Nhs Trust
Emery, Paul D.
United Kingdom, Leeds
Leeds Teaching Hospitals Nhs Trust
Morgan, Ann W.
United Kingdom, Leeds
Leeds Teaching Hospitals Nhs Trust
Bird, Howard Anthony
United Kingdom, Leeds
Leeds Teaching Hospitals Nhs Trust
Conaghan, Philip G.
United Kingdom, Leeds
Leeds Teaching Hospitals Nhs Trust
Pease, Colin Thomas
United Kingdom, Leeds
Leeds Teaching Hospitals Nhs Trust
Wakefield, Richard J.
United Kingdom, Leeds
Leeds Teaching Hospitals Nhs Trust
Mulherin, Diarmuid M.
Unknown Affiliation
Gaffney, Karl
United Kingdom, Norwich
Norfolk and Norwich University Hospitals Nhs Foundation Trust
Macgregor, Alexander
United Kingdom, Norwich
Norfolk and Norwich University Hospitals Nhs Foundation Trust
Birrell, Fraser N.
United Kingdom, North Shields
Northumbria Healthcare Nhs Foundation Trust
Thomas, Allison L.
United Kingdom, Portsmouth
Portsmouth Hospitals University Nhs Trust
Young-Min, Steven A.
United Kingdom, Portsmouth
Portsmouth Hospitals University Nhs Trust
Grindulis, Karl A.
United Kingdom, West Bromwich
Sandwell and West Birmingham Hospitals Nhs Trust
Akil, Mohammed
United Kingdom, Sheffield
Sheffield Teaching Hospitals Nhs Foundation Trust
Edwards, Christopher John
United Kingdom, Southampton
University Hospital Southampton Nhs Foundation Trust
Arden, Nigel K.
United Kingdom, Southampton
University Hospital Southampton Nhs Foundation Trust
Cooper, Cyrus C.
United Kingdom, Southampton
University Hospital Southampton Nhs Foundation Trust
Kitas, George D.
United Kingdom, Dudley
The Dudley Group Nhs Foundation Trust
Foster, Helen Elisabeth
United Kingdom, Newcastle
The Newcastle Upon Tyne Hospitals Nhs Foundation Trust
Griffiths, Bridget
United Kingdom, Newcastle
The Newcastle Upon Tyne Hospitals Nhs Foundation Trust
Grove, Megan L.
United Kingdom, Newcastle
The Newcastle Upon Tyne Hospitals Nhs Foundation Trust
Isaacs, John D.
United Kingdom, Newcastle
The Newcastle Upon Tyne Hospitals Nhs Foundation Trust
Ng, Wan Fai
United Kingdom, Newcastle
The Newcastle Upon Tyne Hospitals Nhs Foundation Trust
Dawes, Peter T.
United Kingdom, Stoke-on-trent
University Hospitals of North Midlands Nhs Trust
Tahir, Hanan I.S.
United Kingdom, London
Barts Health Nhs Trust
Burton, Paul R.
United Kingdom, Leicester
University of Leicester
Clayton, David F.
United Kingdom, London
Wellcome Trust
Cardon, Lon R.
United Kingdom, Oxford
University of Oxford
Craddock, Nick J.
United Kingdom, Cardiff
Cardiff University
Duncanson, Audrey
United Kingdom, London
Wellcome Trust
Kwiatkowski, Dominic P.
United Kingdom, Oxford
University of Oxford
United Kingdom, Hinxton
Wellcome Sanger Institute
McCarthy, Mark I.
United Kingdom, Oxford
University of Oxford
United Kingdom, Oxford
Churchill Hospital
Ouwehand, Willem Hendrik
United Kingdom, Cambridge
University of Cambridge
United Kingdom, Bristol
Nhs Blood and Transplant
Samani, Nilesh J.
United Kingdom, Leicester
Glenfield Hospital
Todd, John A.
United Kingdom, London
Wellcome Trust
Donnelly, Peter J.
United Kingdom, Oxford
University of Oxford
Barrett, Jeffrey C.
United Kingdom, Oxford
University of Oxford
Easton, Douglas F.
United Kingdom, London
Cancer Research uk
Evans, David M.
United Kingdom, Oxford
University of Oxford
Marchini, Jonathan L.
United Kingdom, Oxford
University of Oxford
Morris, Andrew Paul
United Kingdom, Oxford
University of Oxford
Spencer, Chris C.A.
United Kingdom, Oxford
University of Oxford
Tobin, Martin D.
United Kingdom, Leicester
University of Leicester
Attwood, Antony Paul
United Kingdom, Hinxton
Wellcome Sanger Institute
United Kingdom, Cambridge
University of Cambridge
Jolley, Jennifer D.M.
United Kingdom, Cambridge
University of Cambridge
Watkins, Nicholas A.
United Kingdom, Cambridge
University of Cambridge
United Kingdom, Bristol
Nhs Blood and Transplant
Winzer, Thilo
United Kingdom, Cambridge
University of Cambridge
McArdle, Wendy L.
United Kingdom, Bristol
University of Bristol
Ring, Susan M.
United Kingdom, Bristol
University of Bristol
Strachan, David Peter
United Kingdom, London
St George’s, University of London
Pembrey, Marcus E.
United Kingdom, Bristol
University of Bristol
United Kingdom, London
University College London
Breen, Gerome
United Kingdom, Aberdeen
University of Aberdeen
St-Clair, David M.
United Kingdom, Aberdeen
University of Aberdeen
Grozeva, Detelina
United Kingdom, Cardiff
Cardiff University
Holmans, Peter A.
United Kingdom, Cardiff
Cardiff University
Jones, Ian Richard G.
United Kingdom, Cardiff
Cardiff University
O'Donovan, Michael Conlon
United Kingdom, Cardiff
Cardiff University
Owen, Michael John
United Kingdom, Cardiff
Cardiff University
Collier, David Andrew
United Kingdom, London
King's College London
Farmer, Anne E.
United Kingdom, London
King's College London
McGuffin, Peter
United Kingdom, London
King's College London
Young, Allan H.
United Kingdom, Newcastle
Royal Victoria Infirmary
Ball, Stephen Geoffry
United Kingdom, Leeds
University of Leeds
Barrett, J. H.
United Kingdom, Leeds
University of Leeds
Bishop, D. Timothy
United Kingdom, Leeds
University of Leeds
Iles, Mark Martin
United Kingdom, Leeds
University of Leeds
Yuldasheva, Nadira Y.
United Kingdom, Leeds
University of Leeds
Hall, Alistair Scott
United Kingdom, Leeds
University of Leeds
Braund, Peter S.
United Kingdom, Leicester
Glenfield Hospital
Mangino, Massimo
United Kingdom, Leicester
Glenfield Hospital
Thompson, John R.
United Kingdom, Leicester
University of Leicester
Tremelling, Mark A.W.
United Kingdom, Cambridge
Addenbrooke's Hospital
Parkes, Miles
United Kingdom, Cambridge
Addenbrooke's Hospital
Lees, Charlie W.
United Kingdom, Edinburgh
Western General Hospital
Nimmo, Elaine R.
United Kingdom, Edinburgh
Western General Hospital
Satsangi, Jack J.
United Kingdom, Edinburgh
Western General Hospital
Forbes, Alastair
United Kingdom, London
University College London Hospitals Nhs Foundation Trust
Lewis, Cathryn M.
United Kingdom, London
Faculty of Life Sciences & Medicine
Prescott, Natalie J.
United Kingdom, London
Faculty of Life Sciences & Medicine
Sanderson, Jeremy David
United Kingdom, London
Guy's and st Thomas' Nhs Foundation Trust
Mathew, Christopher G.
United Kingdom, London
Faculty of Life Sciences & Medicine
Mansfield, John C.
United Kingdom, Newcastle
Royal Victoria Infirmary
Ahmad, Tariq
United Kingdom, Oxford
Radcliffe Infirmary
Cummings, Fraser R.
United Kingdom, Oxford
Radcliffe Infirmary
Jewell, Derek P.J.
United Kingdom, Oxford
Radcliffe Infirmary
Brown, Morris J.
United Kingdom, Cambridge
Addenbrooke's Hospital
Lathrop, Mark G.
France, Evry
Centre National de Recherche en Génomique Humaine
Dominiczak, Anna F.D.
United Kingdom, Glasgow
University of Glasgow
Dobson, Richard J.B.
United Kingdom, London
Barts and the London School of Medicine and Dentistry
Munroe, Patricia B.
United Kingdom, London
Barts and the London School of Medicine and Dentistry
Caulfield, Mark J.
United Kingdom, London
Barts and the London School of Medicine and Dentistry
Farrall, Martin
United Kingdom, Oxford
University of Oxford
Silman, Allan J.S.
United Kingdom, Manchester
The University of Manchester
Thomson, Wendy
United Kingdom, Manchester
The University of Manchester
Dunger, David B.
United Kingdom, London
Wellcome Trust
United Kingdom, Cambridge
Addenbrooke's Hospital
Frayling, Tim M.
United Kingdom, Plymouth
Peninsula Medical School, Universities of Exeter and Plymouth
Freathy, Rachel M.
United Kingdom, Plymouth
Peninsula Medical School, Universities of Exeter and Plymouth
Perry, John R.B.
United Kingdom, Plymouth
Peninsula Medical School, Universities of Exeter and Plymouth
Shields, Beverley M.
United Kingdom, Plymouth
Peninsula Medical School, Universities of Exeter and Plymouth
Weedon, Michael N.
United Kingdom, Plymouth
Peninsula Medical School, Universities of Exeter and Plymouth
Hattersley, Andrew T.
United Kingdom, Plymouth
Peninsula Medical School, Universities of Exeter and Plymouth
Hitman, Graham A.
United Kingdom, London
Barts and the London School of Medicine and Dentistry
Walker, Mark A.
United Kingdom, Newcastle
Newcastle University
Groves, Christopher James
United Kingdom, Oxford
Churchill Hospital
Lindgren, Cecilia M.
United Kingdom, Oxford
University of Oxford
United Kingdom, Oxford
Churchill Hospital
Rayner, Nigel William
United Kingdom, Oxford
University of Oxford
United Kingdom, Oxford
Churchill Hospital
Timpson, Nicholas J.
United Kingdom, Bristol
University of Bristol
Zeggini, Eleftheria
United Kingdom, Oxford
University of Oxford
United Kingdom, Oxford
Churchill Hospital
Newport, Melanie J.
Gambia, Banjul
Medical Research Council Laboratories Gambia
Sirugo, G.
Gambia, Banjul
Medical Research Council Laboratories Gambia
Lyons, Emily J.
United Kingdom, Oxford
University of Oxford
Gambia, Banjul
Medical Research Council Laboratories Gambia
Vannberg, Fredrik O.
United Kingdom, Oxford
University of Oxford
Hill, Adrian V. S.
United Kingdom, Oxford
University of Oxford
Bradbury, Linda A.
Australia, Woolloongabba
Princess Alexandra Hospital
Pointon, Jennifer J.
Australia, Woolloongabba
Princess Alexandra Hospital
Wordsworth, Paul B.
United Kingdom, Oxford
University of Oxford
Brown, Matthew A.
Australia, Woolloongabba
Princess Alexandra Hospital
United Kingdom, Oxford
University of Oxford
Seal, Sheila
United Kingdom, London
The Institute of Cancer Research
Michael R. Stratton, Michael R.
United Kingdom, London
The Institute of Cancer Research
United Kingdom, Hinxton
Wellcome Sanger Institute
Goris, An
United Kingdom, Cambridge
Addenbrooke's Hospital
Sawcer, Stephen J.
United Kingdom, Cambridge
Addenbrooke's Hospital
Jallow, Muminatou
Gambia, Banjul
Medical Research Council Laboratories Gambia
Rockett, Kirk A.
United Kingdom, Oxford
University of Oxford
Bumpstead, Suzannah J.
United Kingdom, Hinxton
Wellcome Sanger Institute
Downes, Kate A.
United Kingdom, London
Wellcome Trust
United Kingdom, Hinxton
Wellcome Sanger Institute
Ghori, Mohammed J.R.
United Kingdom, Hinxton
Wellcome Sanger Institute
Gwilliam, Rhian G.
United Kingdom, Hinxton
Wellcome Sanger Institute
Inouye, Michael T.
United Kingdom, Hinxton
Wellcome Sanger Institute
McGinnis, Ralph E.
United Kingdom, Hinxton
Wellcome Sanger Institute
Potter, Simon C.
United Kingdom, Hinxton
Wellcome Sanger Institute
Whittaker, Pamela
United Kingdom, Hinxton
Wellcome Sanger Institute
Widden, Claire
United Kingdom, Hinxton
Wellcome Sanger Institute
Withers, David R.
United Kingdom, Hinxton
Wellcome Sanger Institute
Ferreira, Teresa
United Kingdom, Oxford
University of Oxford
Howie, Bryan N.
United Kingdom, Oxford
University of Oxford
Su, Zhan
United Kingdom, Oxford
University of Oxford
Vukcevic, Damjan
United Kingdom, Oxford
University of Oxford
Bentley, David R.
United Kingdom, Hinxton
Wellcome Sanger Institute
Statistics
Citations: 491
Authors: 183
Affiliations: 81
Identifiers
Doi:
10.1038/ng.2462
ISSN:
10614036
Research Areas
Genetics And Genomics
Study Approach
Systematic review