Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis
Author
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Benjamin F. Voight
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Laura J. Scott
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Valgerdur Steinthorsdottir
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Andrew P. Morris
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Christian Dina
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Ryan P. Welch
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Eleftheria Zeggini
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Cornelia Huth
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Yurii S. Aulchenko
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Gudmar Thorleifsson
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Laura J. McCulloch
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Teresa Ferreira
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Harald Grallert
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Najaf Amin
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Guanming Wu
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Cristen J. Willer
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Soumya Raychaudhuri
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Steve A. McCarroll
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Claudia Langenberg
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Oliver M. Hofmann
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Josee Dupuis
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Lu Qi
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Ayellet V. Segre
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Mandy van Hoek
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Pau Navarro
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Kristin Ardlie
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Beverley Balkau
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Rafn Benediktsson
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Amanda J. Bennett
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Roza Blagieva
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Eric Boerwinkle
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Lori L. Bonnycastle
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Kristina Bengtsson Bostrom
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Bert Bravenboer
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Suzannah Bumpstead
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Noisel P. Burtt
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Guillaume Charpentier
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Peter S. Chines
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Marilyn Cornelis
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David J. Couper
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Gabe Crawford
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Alex S. F. Doney
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Katherine S. Elliott
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Amanda L. Elliott
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Michael R. Erdos
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Caroline S. Fox
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Christopher S. Franklin
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Martha Ganser
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Christian Gieger
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Niels Grarup
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Todd Green
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Simon Griffin
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Christopher J. Groves
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Candace Guiducci
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Samy Hadjadj
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Neelam Hassanali
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Christian Herder
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Bo Isomaa
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Anne U. Jackson
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Paul R. V. Johnson
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Torben Jorgensen
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Wen H. L. Kao
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Norman Klopp
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Augustine Kong
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Peter Kraft
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Johanna Kuusisto
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Torsten Lauritzen
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Man Li
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Aloysius Lieverse
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Cecilia M. Lindgren
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Valeriya Lyssenko
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Michel Marre
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Thomas Meitinger
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Kristian Midthjell
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Mario A. Morken
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Narisu Narisu
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Peter Nilsson
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Katharine R. Owen
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Felicity Payne
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John R. B. Perry
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Ann-Kristin Petersen
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Carl Platou
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Christine Proenca
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Inga Prokopenko
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Wolfgang Rathmann
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N. William Rayner
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Neil R. Robertson
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Ghislain Rocheleau
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Michael Roden
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Michael J. Sampson
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Richa Saxena
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Beverley M. Shields
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Peter Shrader
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Gunnar Sigurdsson
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Thomas Sparso
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Klaus Strassburger
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Heather M. Stringham
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Qi Sun
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Amy J. Swift
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Barbara Thorand
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Jean Tichet
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Tiinamaija Tuomi
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Rob M. van Dam
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Timon W. van Haeften
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Thijs van Herpt
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Jana V. van Vliet-Ostaptchouk
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G. Bragi Walters
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Michael N. Weedon
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Cisca Wijmenga
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Jacqueline Witteman
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Richard N. Bergman
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Stephane Cauchi
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Francis S. Collins
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Anna L. Gloyn
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Ulf Gyllensten
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Torben Hansen
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Winston A. Hide
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Graham A. Hitman
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Albert Hofman
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David J. Hunter
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Kristian Hveem
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Markku Laakso
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Karen L. Mohlke
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Andrew D. Morris
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Colin N. A. Palmer
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Peter P. Pramstaller
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Igor Rudan
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Eric Sijbrands
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Lincoln D. Stein
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Jaakko Tuomilehto
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Andre Uitterlinden
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Mark Walker
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Nicholas J. Wareham
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Richard M. Watanabe
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Goncalo R. Abecasis
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Bernhard O. Boehm
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Harry Campbell
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Mark J. Daly
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Andrew T. Hattersley
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Frank B. Hu
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James B. Meigs
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James S. Pankow
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Oluf Pedersen
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H-Erich Wichmann
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Ines Barroso
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Jose C. Florez
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Timothy M. Frayling
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Leif Groop
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Rob Sladek
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Unnur Thorsteinsdottir
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James F. Wilson
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Thomas Illig
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Philippe Froguel
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Cornelia M. van Duijn
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Kari Stefansson
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David Altshuler
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Michael Boehnke
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Mark I. McCarthy
Summary, in English
By combining genome-wide association data from 8,130 individuals with type 2 diabetes (T2D) and 38,987 controls of European descent and following up previously unidentified meta-analysis signals in a further 34,412 cases and 59,925 controls, we identified 12 new T2D association signals with combined P < 5 x 10(-8). These include a second independent signal at the KCNQ1 locus; the first report, to our knowledge, of an X-chromosomal association (near DUSP9); and a further instance of overlap between loci implicated in monogenic and multifactorial forms of diabetes (at HNF1A). The identified loci affect both beta-cell function and insulin action, and, overall, T2D association signals show evidence of enrichment for genes involved in cell cycle regulation. We also show that a high proportion of T2D susceptibility loci harbor independent association signals influencing apparently unrelated complex traits.