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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Fine mapping of type 1 diabetes susceptibility loci and evidence for colocalization of causal variants with lymphoid gene enhancers
Nature Genetics, Volume 47, No. 4, Year 2015
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Description
Genetic studies of type 1 diabetes (T1D) have identified 50 susceptibility regions, finding major pathways contributing to risk, with some loci shared across immune disorders. To make genetic comparisons across autoimmune disorders as informative as possible, a dense genotyping array, the Immunochip, was developed, from which we identified four new T1D-associated regions (P < 5 × 10-8). A comparative analysis with 15 immune diseases showed that T1D is more similar genetically to other autoantibody-positive diseases, significantly most similar to juvenile idiopathic arthritis and significantly least similar to ulcerative colitis, and provided support for three additional new T1D risk loci. Using a Bayesian approach, we defined credible sets for the T1D-associated SNPs. The associated SNPs localized to enhancer sequences active in thymus, T and B cells, and CD34 + stem cells. Enhancer-promoter interactions can now be analyzed in these cell types to identify which particular genes and regulatory sequences are causal. © 2015 Nature America, Inc. All rights reserved.
Authors & Co-Authors
Önengüt-Gümüşcü, Suna
United States, Charlottesville
University of Virginia
Chen, Weimin
United States, Charlottesville
University of Virginia
Mychaleckyj, Josyf C.
United States, Charlottesville
University of Virginia
Farber, Emily A.
United States, Charlottesville
University of Virginia
Szpak, Michał
United States, Charlottesville
University of Virginia
Schofield, Ellen C.
United Kingdom, Cambridge
Addenbrooke's Hospital
Fortune, Mary D.
United Kingdom, Cambridge
Addenbrooke's Hospital
Kundaje, Anshul B.
United States, Cambridge
Massachusetts Institute of Technology
United States, Palo Alto
Stanford University
United States, Boston
Massachusetts General Hospital
Kellis, Manolis
United States, Cambridge
Massachusetts Institute of Technology
Daly, Mark J.
United States, Cambridge
Massachusetts Institute of Technology
United States, Boston
Massachusetts General Hospital
Barrett, Jeffrey C.
United Kingdom, Hinxton
Wellcome Sanger Institute
Cooper, Jason D.
United Kingdom, Cambridge
Addenbrooke's Hospital
Deloukas, Panos
United Kingdom, Hinxton
Wellcome Sanger Institute
Todd, John A.
United Kingdom, Cambridge
Addenbrooke's Hospital
Concannon, Patrick
United States, Charlottesville
University of Virginia
United States, Gainesville
University of Florida
Rich, Stephen S.
United States, Charlottesville
University of Virginia
Baskerville, Tracey
Unknown Affiliation
Bautista, Nines
Unknown Affiliation
Bhatia, Eesh
Unknown Affiliation
Bhatia, Vijayalakshmi L.
Unknown Affiliation
Bonnici, François B.
Unknown Affiliation
Brodnicki, Thomas C.
Unknown Affiliation
Browning, Brian L.
Unknown Affiliation
Cameron, Fergus J.
Unknown Affiliation
Chaichanwatanakul, Katharee
Unknown Affiliation
Cheung, Pik To
Unknown Affiliation
Colman, P. G.
Unknown Affiliation
Cotterill, Andrew Michael
Unknown Affiliation
Couper, Jennifer J.
Unknown Affiliation
Crock, Patricia A.
Unknown Affiliation
Cutfield, Ric
Unknown Affiliation
Davis, Timothy M.E.
Unknown Affiliation
Dixon, Paul
Unknown Affiliation
Donaghue, Kim C.
Unknown Affiliation
Dowling, Katrina
Unknown Affiliation
Drury, Paul Leslie
Unknown Affiliation
Dye, Sarah
Unknown Affiliation
Gellert, Shane A.
Unknown Affiliation
Abdul Ghani, Rohana
Unknown Affiliation
Greer, R. M.
Unknown Affiliation
Harrison, L. C.
Unknown Affiliation
Homatopoulos, Nick
Unknown Affiliation
Ji, Linong
Unknown Affiliation
Jones, Timothy W.
Unknown Affiliation
Kamaruddin, Nor Azmi Zmi
Unknown Affiliation
Kanga, Uma
Unknown Affiliation
Kanungo, Alok
Unknown Affiliation
Kaur, Gurvinder
Unknown Affiliation
Kek, Betty Lay Kee
Unknown Affiliation
Knowles, Simon
Unknown Affiliation
Krebs, Jeremy D.
Unknown Affiliation
Lee, Yannjinn
Unknown Affiliation
Liktimaskul, Supawadee
Unknown Affiliation
Lloyd, Margaret
Unknown Affiliation
Loth, Amanda
Unknown Affiliation
Louey, Anthony
Unknown Affiliation
Mehra, Narinder Kumar
Unknown Affiliation
Merriman, Tony R.
Unknown Affiliation
Min, Liu
Unknown Affiliation
Morahan, Grant E.
Unknown Affiliation
Moses, Robert Geoffrey
Unknown Affiliation
Mraz, Grant A.
Unknown Affiliation
Murphy, Rinki P.
Unknown Affiliation
Nicholson, Ian C.
Unknown Affiliation
Panelo, Araceli A.
Unknown Affiliation
Poh, Perlita
Unknown Affiliation
Price, Gareth R.
Unknown Affiliation
Ratnam, Nirubasini
Unknown Affiliation
Sanjeevi, Carani Balaraman
Unknown Affiliation
Sedimbi, Saikiran K.
Unknown Affiliation
Shen, Shuixian
Unknown Affiliation
Tait, Brian D.
Unknown Affiliation
Tandon, Nikhil
Unknown Affiliation
Thomas, Allison L.
Unknown Affiliation
Varney, Michael D.
Unknown Affiliation
Weerakulwattana, Praewvarin
Unknown Affiliation
Willis, Jinny
Unknown Affiliation
Akwo, Elvis Abang
Unknown Affiliation
Albret, Lotte
Unknown Affiliation
Ampudia-Blasco, Francisco Javier
Unknown Affiliation
Argenté, Jésus
Unknown Affiliation
Avbelj Stefanija, Magdalena
Unknown Affiliation
Babadjanova, Goulnara
Unknown Affiliation
Badenhoop, Klaus
Unknown Affiliation
Battelino, Tadej
Unknown Affiliation
Beilhack, Georg F.
Unknown Affiliation
Bergholdt, Regine
Unknown Affiliation
Böehm, Bernhard Otto
Unknown Affiliation
Bolidson, Jo
Unknown Affiliation
Brismar, Kerstin E.
Unknown Affiliation
Brorsson, Caroline Anna B.
Unknown Affiliation
Carlson, Joyce A.
Unknown Affiliation
Castaño, Luís Antonio
Unknown Affiliation
Chandler, Kyla A.
Unknown Affiliation
Cherubini, Valentino
Unknown Affiliation
Cinek, Ondr̂ej
Unknown Affiliation
Cipponeri, Elisa
Unknown Affiliation
Corripio, Raquel
Unknown Affiliation
Guja, Cristian
Unknown Affiliation
Gutiérrez, Pilar
Unknown Affiliation
Heath, Simon C.
Unknown Affiliation
Hernández García, Marta José Rabanaque
Unknown Affiliation
Ilonen, Jorma S.
Unknown Affiliation
Julier, Cécile
Unknown Affiliation
Knip, Mikael J.
Unknown Affiliation
Kockum, Ingrid Skelton
Unknown Affiliation
Kordonouri, Olga
Unknown Affiliation
Ludvigsson, Johnny G.
Unknown Affiliation
Mauricio, Dídac P.
Unknown Affiliation
Phillip, Moshe
Unknown Affiliation
Pirags, Valdis
Unknown Affiliation
Pociot, Flemming Michael
Unknown Affiliation
Pozzilli, Paolo
Unknown Affiliation
Roep, Bart O.
Unknown Affiliation
Rubio-Cabezas, Óscar
Unknown Affiliation
Satman, İlhan
Unknown Affiliation
Schober, Edith
Unknown Affiliation
Seufert, Jochen R.
Unknown Affiliation
Sobngwi, Eugène
Unknown Affiliation
Spinas, Giatgen Andreia
Unknown Affiliation
Šumník, Zdeněk
Unknown Affiliation
Undlien, Dag Erik
Unknown Affiliation
der Auwera, Bart Van
Unknown Affiliation
Veličkienė, Džilda
Unknown Affiliation
Wägner, Ana María
Unknown Affiliation
Walter, Markus
Unknown Affiliation
Williams, Alistair J.K.
Unknown Affiliation
Ziegler, Anette Gabriele
Unknown Affiliation
Aldrich, Alan
Unknown Affiliation
Alper, Chester A.
Unknown Affiliation
Becker, Dorothy J.
Unknown Affiliation
Benoist, Christophe O.
Unknown Affiliation
Berka, Noureddine
Unknown Affiliation
Bottini, Nunzio
Unknown Affiliation
Brickman, Wendy J.
Unknown Affiliation
Couch, Robert M.
Unknown Affiliation
Dolan, Lawrence M.
Unknown Affiliation
Doria, Alessandro
Unknown Affiliation
Fain, Pamela R.
Unknown Affiliation
Geraghty, Daniel E.
Unknown Affiliation
Greenbaum, Carla J.
Unknown Affiliation
Hagopian, William A.
Unknown Affiliation
Håkonarson, Håkon H.
Unknown Affiliation
Hansen, John A.
Unknown Affiliation
Kaiserman, Kevin B.
Unknown Affiliation
Lane, Julie Ann
Unknown Affiliation
Moonsamy, Priscilla V.
Unknown Affiliation
Moran, Antoinette M.
Unknown Affiliation
Noble, Janelle Annette
Unknown Affiliation
Orbán, Tihamér
Unknown Affiliation
Paterson, Andrew D.
Unknown Affiliation
Pietropaolo, Massimo
Unknown Affiliation
Pihoker, Catherine M.
Unknown Affiliation
Polychronakos, Constantin
Unknown Affiliation
Pugliese, Alberto
Unknown Affiliation
Qu, Huiqi
Unknown Affiliation
Schatz, Desmond A.
Unknown Affiliation
She, Jinxiong
Unknown Affiliation
Steck, Andrea K.
Unknown Affiliation
Taback, Shayne P.
Unknown Affiliation
Willi, Steven M.
Unknown Affiliation
Yu, Liping
Unknown Affiliation
Zhao, Lueping
Unknown Affiliation
Allen, Jamie E.
Unknown Affiliation
Cucca, Francesco
Unknown Affiliation
Downes, Kate A.
Unknown Affiliation
Dunger, David B.
Unknown Affiliation
Field, Sarah F.
Unknown Affiliation
Howson, Joanna M.M.
Unknown Affiliation
Plagnol, Vincent
Unknown Affiliation
Tuomilehto, Jaakko O.I.
Unknown Affiliation
Wicker, Linda S.
Unknown Affiliation
Hepler, John
Unknown Affiliation
Lohman, Kurt K.
Unknown Affiliation
Perdue, Letitia H.
Unknown Affiliation
Pierce, June J.
Unknown Affiliation
Rushing, Scott
Unknown Affiliation
Sides, Elizabeth G.
Unknown Affiliation
Snively, Beverly M.
Unknown Affiliation
Wagenknecht, Lynne E.
Unknown Affiliation
Akolkar, Beena
Unknown Affiliation
Nierras, Concepcion R.
Unknown Affiliation
Barcellos, Lisa F.
Unknown Affiliation
Briggs, Farren Basil Shaw
Unknown Affiliation
de Bakker, Paul I.W.
Unknown Affiliation
Devlin, Bernie
Unknown Affiliation
Field, Lanora Leigh
Unknown Affiliation
Gabriel, Stacey Bolk
Unknown Affiliation
Gaudieri, S.
Unknown Affiliation
Gorodezky, C.
Unknown Affiliation
Humphreys, Keith
Unknown Affiliation
James, Ian R.
Unknown Affiliation
Lathrop, Mark G.
Unknown Affiliation
Mack, Steven J.
Unknown Affiliation
McGinnis, Ralph E.
Unknown Affiliation
McLaren, William M.
Unknown Affiliation
Ott, Jürg
Unknown Affiliation
Patterson, Chris C.
Unknown Affiliation
Risch, Neil J.
Unknown Affiliation
Rönningen, Kjersti Skjold
Unknown Affiliation
Single, Richard M.
Unknown Affiliation
Thomson, Glenys J.
Unknown Affiliation
Vandiedonck, Claire
Unknown Affiliation
Whittaker, Pamela
Unknown Affiliation
Zhang, Qingrun
Unknown Affiliation
Statistics
Citations: 564
Authors: 205
Affiliations: 8
Identifiers
Doi:
10.1038/ng.3245
ISSN:
10614036
Research Areas
Cancer
Genetics And Genomics
Noncommunicable Diseases