Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2012-09

AUTHORS

Andrew P Morris, Benjamin F Voight, Tanya M Teslovich, Teresa Ferreira, Ayellet V Segré, Valgerdur Steinthorsdottir, Rona J Strawbridge, Hassan Khan, Harald Grallert, Anubha Mahajan, Inga Prokopenko, Hyun Min Kang, Christian Dina, Tonu Esko, Ross M Fraser, Stavroula Kanoni, Ashish Kumar, Vasiliki Lagou, Claudia Langenberg, Jian’an Luan, Cecilia M Lindgren, Martina Müller-Nurasyid, Sonali Pechlivanis, N William Rayner, Laura J Scott, Steven Wiltshire, Loic Yengo, Leena Kinnunen, Elizabeth J Rossin, Soumya Raychaudhuri, Andrew D Johnson, Antigone S Dimas, Ruth J F Loos, Sailaja Vedantam, Han Chen, Jose C Florez, Caroline Fox, Ching-Ti Liu, Denis Rybin, David J Couper, Wen Hong L Kao, Man Li, Marilyn C Cornelis, Peter Kraft, Qi Sun, Rob M van Dam, Heather M Stringham, Peter S Chines, Krista Fischer, Pierre Fontanillas, Oddgeir L Holmen, Sarah E Hunt, Anne U Jackson, Augustine Kong, Robert Lawrence, Julia Meyer, John R B Perry, Carl G P Platou, Simon Potter, Emil Rehnberg, Neil Robertson, Suthesh Sivapalaratnam, Alena Stančáková, Kathleen Stirrups, Gudmar Thorleifsson, Emmi Tikkanen, Andrew R Wood, Peter Almgren, Mustafa Atalay, Rafn Benediktsson, Lori L Bonnycastle, Noël Burtt, Jason Carey, Guillaume Charpentier, Andrew T Crenshaw, Alex S F Doney, Mozhgan Dorkhan, Sarah Edkins, Valur Emilsson, Elodie Eury, Tom Forsen, Karl Gertow, Bruna Gigante, George B Grant, Christopher J Groves, Candace Guiducci, Christian Herder, Astradur B Hreidarsson, Jennie Hui, Alan James, Anna Jonsson, Wolfgang Rathmann, Norman Klopp, Jasmina Kravic, Kaarel Krjutškov, Cordelia Langford, Karin Leander, Eero Lindholm, Stéphane Lobbens, Satu Männistö, Ghazala Mirza, Thomas W Mühleisen, Bill Musk, Melissa Parkin, Loukianos Rallidis, Jouko Saramies, Bengt Sennblad, Sonia Shah, Gunnar Sigurðsson, Angela Silveira, Gerald Steinbach, Barbara Thorand, Joseph Trakalo, Fabrizio Veglia, Roman Wennauer, Wendy Winckler, Delilah Zabaneh, Harry Campbell, Cornelia van Duijn, Andre G Uitterlinden, Albert Hofman, Eric Sijbrands, Goncalo R Abecasis, Katharine R Owen, Eleftheria Zeggini, Mieke D Trip, Nita G Forouhi, Ann-Christine Syvänen, Johan G Eriksson, Leena Peltonen, Markus M Nöthen, Beverley Balkau, Colin N A Palmer, Valeriya Lyssenko, Tiinamaija Tuomi, Bo Isomaa, David J Hunter, Lu Qi, , , , , , Alan R Shuldiner, Michael Roden, Ines Barroso, Tom Wilsgaard, John Beilby, Kees Hovingh, Jackie F Price, James F Wilson, Rainer Rauramaa, Timo A Lakka, Lars Lind, George Dedoussis, Inger Njølstad, Nancy L Pedersen, Kay-Tee Khaw, Nicholas J Wareham, Sirkka M Keinanen-Kiukaanniemi, Timo E Saaristo, Eeva Korpi-Hyövälti, Juha Saltevo, Markku Laakso, Johanna Kuusisto, Andres Metspalu, Francis S Collins, Karen L Mohlke, Richard N Bergman, Jaakko Tuomilehto, Bernhard O Boehm, Christian Gieger, Kristian Hveem, Stephane Cauchi, Philippe Froguel, Damiano Baldassarre, Elena Tremoli, Steve E Humphries, Danish Saleheen, John Danesh, Erik Ingelsson, Samuli Ripatti, Veikko Salomaa, Raimund Erbel, Karl-Heinz Jöckel, Susanne Moebus, Annette Peters, Thomas Illig, Ulf de Faire, Anders Hamsten, Andrew D Morris, Peter J Donnelly, Timothy M Frayling, Andrew T Hattersley, Eric Boerwinkle, Olle Melander, Sekar Kathiresan, Peter M Nilsson, Panos Deloukas, Unnur Thorsteinsdottir, Leif C Groop, Kari Stefansson, Frank Hu, James S Pankow, Josée Dupuis, James B Meigs, David Altshuler, Michael Boehnke, Mark I McCarthy,

ABSTRACT

To extend understanding of the genetic architecture and molecular basis of type 2 diabetes (T2D), we conducted a meta-analysis of genetic variants on the Metabochip, including 34,840 cases and 114,981 controls, overwhelmingly of European descent. We identified ten previously unreported T2D susceptibility loci, including two showing sex-differentiated association. Genome-wide analyses of these data are consistent with a long tail of additional common variant loci explaining much of the variation in susceptibility to T2D. Exploration of the enlarged set of susceptibility loci implicates several processes, including CREBBP-related transcription, adipocytokine signaling and cell cycle regulation, in diabetes pathogenesis. More... »

PAGES

981

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  • Journal

    TITLE

    Nature Genetics

    ISSUE

    9

    VOLUME

    44

    Author Affiliations

  • Wellcome Centre for Human Genetics
  • University of Pennsylvania
  • University of Michigan–Ann Arbor
  • Harvard University
  • deCODE Genetics (Iceland)
  • Karolinska University Hospital
  • University of Cambridge
  • Helmholtz Zentrum München
  • University of Oxford
  • University of Nantes
  • University of Tartu
  • University of Edinburgh
  • Wellcome Sanger Institute
  • Ludwig Maximilian University of Munich
  • Lille 1 University
  • National Institute for Health and Welfare
  • Broad Institute
  • National Heart Lung and Blood Institute
  • Alexander Fleming Biomedical Sciences Research Center
  • Icahn School of Medicine at Mount Sinai
  • Boston Children's Hospital
  • Boston University
  • Massachusetts General Hospital
  • University of North Carolina at Chapel Hill
  • Johns Hopkins University
  • National University of Singapore
  • National Human Genome Research Institute
  • Norwegian University of Science and Technology
  • University of Western Australia
  • University of Exeter
  • Levanger Hospital
  • Karolinska Institute
  • Lund University
  • University of Eastern Finland
  • National University Hospital of Iceland
  • Icelandic Heart Association
  • Institut de Biologie de Lille
  • University of Helsinki
  • German Diabetes Center - Leibniz Institute for Diabetes Research at Heinrich Heine University Düsseldorf
  • University of Bonn
  • Sir Charles Gairdner Hospital
  • University General Hospital Attikon
  • South Karelia Central Hospital
  • University College London
  • University of Ulm
  • Centro Cardiologico Monzino
  • Western General Hospital
  • Erasmus University Medical Center
  • Churchill Hospital
  • Uppsala University
  • Folkhälsans Forskningscentrum
  • University of Paris-Sud
  • University of Maryland, Baltimore
  • Heinrich Heine University Düsseldorf
  • Institute of Metabolic Science
  • The Arctic University of Norway
  • Kuopio University Hospital
  • Kuopion Liikuntalääketieteen Tutkimuslaitos
  • Harokopio University
  • Oulu University Hospital
  • Pirkanmaa Hospital District
  • Seinäjoen Keskussairaala
  • Central Finland Health Care District
  • University of Southern California
  • Danube University Krems
  • Imperial College London
  • University of Milan
  • Center for Non-Communicable Diseases
  • Hannover Medical School
  • Baylor College of Medicine
  • University of Iceland
  • University of Minnesota
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ng.2383

    DOI

    http://dx.doi.org/10.1038/ng.2383

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1011024359

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/22885922


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