Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis

Benjamin F. Voight; Laura J. Scott; Valgerdur Steinthorsdottir; Andrew P. Morris; Christian Dina; Ryan P. Welch; Eleftheria Zeggini; Cornelia Huth; Yurii S. Aulchenko; Gudmar Thorleifsson; Laura J. McCulloch; Teresa Ferreira; Harald Grallert; Najaf Amin; Guanming Wu; Cristen J. Willer; Soumya Raychaudhuri; Steve A. McCarroll; Claudia Langenberg; Oliver M. Hofmann; Josee Dupuis; Lu Qi; Ayellet V. Segre; Mandy van Hoek; Pau Navarro; Kristin Ardlie; Beverley Balkau; Rafn Benediktsson; Amanda J. Bennett; Roza Blagieva; Eric Boerwinkle; Lori L. Bonnycastle; Kristina Bengtsson Bostrom; Bert Bravenboer; Suzannah Bumpstead; Noisel P. Burtt; Guillaume Charpentier; Peter S. Chines; Marilyn Cornelis; David J. Couper; Gabe Crawford; Alex S. F. Doney; Katherine S. Elliott; Amanda L. Elliott; Michael R. Erdos; Caroline S. Fox; Christopher S. Franklin; Martha Ganser; Christian Gieger; Niels Grarup; Todd Green; Simon Griffin; Christopher J. Groves; Candace Guiducci; Samy Hadjadj; Neelam Hassanali; Christian Herder; Bo Isomaa; Anne U. Jackson; Paul R. V. Johnson; Torben Jorgensen; Wen H. L. Kao; Norman Klopp; Augustine Kong; Peter Kraft; Johanna Kuusisto; Torsten Lauritzen; Man Li; Aloysius Lieverse; Cecilia M. Lindgren; Valeriya Lyssenko; Michel Marre; Thomas Meitinger; Kristian Midthjell; Mario A. Morken; Narisu Narisu; Peter Nilsson; Katharine R. Owen; Felicity Payne; John R. B. Perry; Ann-Kristin Petersen; Carl Platou; Christine Proenca; Inga Prokopenko; Wolfgang Rathmann; N. William Rayner; Neil R. Robertson; Ghislain Rocheleau; Michael Roden; Michael J. Sampson; Richa Saxena; Beverley M. Shields; Peter Shrader; Gunnar Sigurdsson; Thomas Sparso; Klaus Strassburger; Heather M. Stringham; Qi Sun; Amy J. Swift; Barbara Thorand; GIANT Consortium

doi:10.1038/ng.609

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Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis

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Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis

Benjamin F. Voight, Laura J. Scott, Valgerdur Steinthorsdottir, Andrew P. Morris, Christian Dina, Ryan P. Welch, Eleftheria Zeggini, Cornelia Huth, Yurii S. Aulchenko, Gudmar Thorleifsson, …

Nature genetics, Vol.42(7), pp.579-U155

01/07/2010

DOI: https://doi.org/10.1038/ng.609

PMID: 20581827

Abstract

Genetics & Heredity

Life Sciences & Biomedicine

Science & Technology

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.

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Title: Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis
Creators: Benjamin F. Voight - Broad Institute
Laura J. Scott - University of Michigan–Ann Arbor
Valgerdur Steinthorsdottir - deCODE Genet, Reykjavik, Iceland
Andrew P. Morris - Wellcome Centre for Human Genetics
Christian Dina - Institut Pasteur de Lille
Ryan P. Welch - University of Michigan–Ann Arbor
Eleftheria Zeggini - Wellcome Centre for Human Genetics
Cornelia Huth - Helmholtz Zentrum München
Yurii S. Aulchenko - Erasmus MC
Gudmar Thorleifsson - deCODE Genet, Reykjavik, Iceland
Laura J. McCulloch - Oxford Centre for Diabetes, Endocrinology and Metabolism
Teresa Ferreira - Wellcome Centre for Human Genetics
Harald Grallert - Helmholtz Zentrum München
Najaf Amin - Erasmus MC
Guanming Wu - Ontario Institute for Cancer Research
Cristen J. Willer - University of Michigan–Ann Arbor
Soumya Raychaudhuri - Center for Human Genetics
Steve A. McCarroll - Broad Institute
Claudia Langenberg - MRC Epidemiology Unit
Oliver M. Hofmann - Harvard University
Josee Dupuis - Boston University
Lu Qi - Harvard University
Ayellet V. Segre - Center for Human Genetics
Mandy van Hoek - Erasmus University Rotterdam
Pau Navarro - MRC Institute of Genetics and Molecular Medicine
Kristin Ardlie - Broad Institute
Beverley Balkau - Centre de recherche en Epidémiologie et Santé des Populations
Rafn Benediktsson - National University Hospital of Iceland
Amanda J. Bennett - University of Oxford
Roza Blagieva - Universität Ulm
Eric Boerwinkle - The University of Texas Health Science Center at Houston
Lori L. Bonnycastle - National Human Genome Research Institute
Kristina Bengtsson Bostrom - Skaraborg Hospital
Bert Bravenboer - Catharina Ziekenhuis
Suzannah Bumpstead - Wellcome Sanger Institute
Noisel P. Burtt - Broad Institute
Guillaume Charpentier - Centre Hospitalier Sud Francilien
Peter S. Chines - National Human Genome Research Institute
Marilyn Cornelis - Harvard University
David J. Couper - University of North Carolina at Chapel Hill
Gabe Crawford - Broad Institute
Alex S. F. Doney - Ninewells Hospital
Katherine S. Elliott - University of Oxford
Amanda L. Elliott - Broad Institute
Michael R. Erdos - National Human Genome Research Institute
Caroline S. Fox - Framingham Heart Study
Christopher S. Franklin - University of Edinburgh
Martha Ganser - University of Michigan–Ann Arbor
Christian Gieger - Helmholtz Zentrum München
Niels Grarup - Hagedorn Res Inst, Gentofte, Denmark
Todd Green - Center for Human Genetics
Simon Griffin - MRC Epidemiology Unit
Christopher J. Groves - Oxford Centre for Diabetes, Endocrinology and Metabolism
Candace Guiducci - Massachusetts Institute of Technology
Samy Hadjadj - Centre Hospitalier Universitaire de Poitiers
Neelam Hassanali - Oxford Centre for Diabetes, Endocrinology and Metabolism
Christian Herder - Deutsches Diabetes-Zentrum e.V.
Bo Isomaa - Folkhälsans Forskningscentrum
Anne U. Jackson - University of Michigan–Ann Arbor
Paul R. V. Johnson - University of Oxford
Torben Jorgensen - Glostrup Univ Hosp, Res Ctr Prevent & Hlth, Glostrup, Denmark
Wen H. L. Kao - Johns Hopkins University
Norman Klopp - Helmholtz Zentrum München
Augustine Kong - deCODE Genetics
Peter Kraft - Harvard University
Johanna Kuusisto - Kuopio University Hospital
Torsten Lauritzen - Aarhus University
Man Li - Erasmus MC
Aloysius Lieverse - Máxima Medisch Centrum
Cecilia M. Lindgren - University of Oxford
Valeriya Lyssenko - Lund University
Michel Marre - Hôpital Bichat-Claude-Bernard
Thomas Meitinger - Helmholtz Zentrum München
Kristian Midthjell - Norwegian University of Science and Technology
Mario A. Morken - National Human Genome Research Institute
Narisu Narisu - National Human Genome Research Institute
Peter Nilsson - Lund University
Katharine R. Owen - University of Oxford
Felicity Payne - Wellcome Sanger Institute
John R. B. Perry - University of Exeter
Ann-Kristin Petersen - Helmholtz Zentrum München
Carl Platou - College Station Medical Center
Christine Proenca - Institut Pasteur de Lille
Inga Prokopenko - Oxford Centre for Diabetes, Endocrinology and Metabolism
Wolfgang Rathmann - Deutsches Diabetes-Zentrum e.V.
N. William Rayner - University of Oxford
Neil R. Robertson - University of Oxford
Ghislain Rocheleau - McGill University
Michael Roden - Deutsches Diabetes-Zentrum e.V.
Michael J. Sampson - Norfolk and Norwich University Hospital
Richa Saxena - Harvard University
Beverley M. Shields - University of Exeter
Peter Shrader - Harvard University
Gunnar Sigurdsson - Landspitali Univ Hosp, Reykjavik, Iceland
Thomas Sparso - Hagedorn Res Inst, Gentofte, Denmark
Klaus Strassburger - Univ Dusseldorf, Leibniz Ctr Diabet Res, German Diabet Ctr, Inst Biometr & Epidemiol, Dusseldorf, Germany
Heather M. Stringham - University of Michigan–Ann Arbor
Qi Sun - Harvard University
Amy J. Swift - National Human Genome Research Institute
Barbara Thorand - Helmholtz Zentrum München
GIANT Consortium
Publication Details: Nature genetics, Vol.42(7), pp.579-U155
Publisher: NATURE PORTFOLIO
Number of pages: 13
Date published: 01/07/2010
Grant note: DHCS/07/07/008 / National Institute for Health Research; National Institutes of Health Research (NIHR) G0700222; MC_U106179474; G0600331; G0601261; G0701863; MC_U127592696 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) CZB/4/710 / Chief Scientist Office MC_U127592696; G0700222; MC_U106179474; MC_U106179471; G0600331; G0701863; G0601261 / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC)
Identifiers: 99928603902346
Academic Unit: School of Biosciences
Language: English
Resource Type: Journal article

Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis

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