New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2010-02

AUTHORS

Josée Dupuis, Claudia Langenberg, Inga Prokopenko, Richa Saxena, Nicole Soranzo, Anne U Jackson, Eleanor Wheeler, Nicole L Glazer, Nabila Bouatia-Naji, Anna L Gloyn, Cecilia M Lindgren, Reedik Mägi, Andrew P Morris, Joshua Randall, Toby Johnson, Paul Elliott, Denis Rybin, Gudmar Thorleifsson, Valgerdur Steinthorsdottir, Peter Henneman, Harald Grallert, Abbas Dehghan, Jouke Jan Hottenga, Christopher S Franklin, Pau Navarro, Kijoung Song, Anuj Goel, John R B Perry, Josephine M Egan, Taina Lajunen, Niels Grarup, Thomas Sparsø, Alex Doney, Benjamin F Voight, Heather M Stringham, Man Li, Stavroula Kanoni, Peter Shrader, Christine Cavalcanti-Proença, Meena Kumari, Lu Qi, Nicholas J Timpson, Christian Gieger, Carina Zabena, Ghislain Rocheleau, Erik Ingelsson, Ping An, Jeffrey O’Connell, Jian'an Luan, Amanda Elliott, Steven A McCarroll, Felicity Payne, Rosa Maria Roccasecca, François Pattou, Praveen Sethupathy, Kristin Ardlie, Yavuz Ariyurek, Beverley Balkau, Philip Barter, John P Beilby, Yoav Ben-Shlomo, Rafn Benediktsson, Amanda J Bennett, Sven Bergmann, Murielle Bochud, Eric Boerwinkle, Amélie Bonnefond, Lori L Bonnycastle, Knut Borch-Johnsen, Yvonne Böttcher, Eric Brunner, Suzannah J Bumpstead, Guillaume Charpentier, Yii-Der Ida Chen, Peter Chines, Robert Clarke, Lachlan J M Coin, Matthew N Cooper, Marilyn Cornelis, Gabe Crawford, Laura Crisponi, Ian N M Day, Eco de Geus, Jerome Delplanque, Christian Dina, Michael R Erdos, Annette C Fedson, Antje Fischer-Rosinsky, Nita G Forouhi, Caroline S Fox, Rune Frants, Maria Grazia Franzosi, Pilar Galan, Mark O Goodarzi, Jürgen Graessler, Christopher J Groves, Scott Grundy, Rhian Gwilliam, Ulf Gyllensten, Samy Hadjadj, Göran Hallmans, Naomi Hammond, Xijing Han, Anna-Liisa Hartikainen, Neelam Hassanali, Caroline Hayward, Simon C Heath, Serge Hercberg, Christian Herder, Andrew A Hicks, David R Hillman, Aroon D Hingorani, Albert Hofman, Jennie Hui, Joe Hung, Bo Isomaa, Paul R V Johnson, Torben Jørgensen, Antti Jula, Marika Kaakinen, Jaakko Kaprio, Y Antero Kesaniemi, Mika Kivimaki, Beatrice Knight, Seppo Koskinen, Peter Kovacs, Kirsten Ohm Kyvik, G Mark Lathrop, Debbie A Lawlor, Olivier Le Bacquer, Cécile Lecoeur, Yun Li, Valeriya Lyssenko, Robert Mahley, Massimo Mangino, Alisa K Manning, María Teresa Martínez-Larrad, Jarred B McAteer, Laura J McCulloch, Ruth McPherson, Christa Meisinger, David Melzer, David Meyre, Braxton D Mitchell, Mario A Morken, Sutapa Mukherjee, Silvia Naitza, Narisu Narisu, Matthew J Neville, Ben A Oostra, Marco Orrù, Ruth Pakyz, Colin N A Palmer, Giuseppe Paolisso, Cristian Pattaro, Daniel Pearson, John F Peden, Nancy L. Pedersen, Markus Perola, Andreas F H Pfeiffer, Irene Pichler, Ozren Polasek, Danielle Posthuma, Simon C Potter, Anneli Pouta, Michael A Province, Bruce M Psaty, Wolfgang Rathmann, Nigel W Rayner, Kenneth Rice, Samuli Ripatti, Fernando Rivadeneira, Michael Roden, Olov Rolandsson, Annelli Sandbaek, Manjinder Sandhu, Serena Sanna, Avan Aihie Sayer, Paul Scheet, Laura J Scott, Udo Seedorf, Stephen J Sharp, Beverley Shields, Gunnar Sigurðsson, Erik J G Sijbrands, Angela Silveira, Laila Simpson, Andrew Singleton, Nicholas L Smith, Ulla Sovio, Amy Swift, Holly Syddall, Ann-Christine Syvänen, Toshiko Tanaka, Barbara Thorand, Jean Tichet, Anke Tönjes, Tiinamaija Tuomi, André G Uitterlinden, Ko Willems van Dijk, Mandy van Hoek, Dhiraj Varma, Sophie Visvikis-Siest, Veronique Vitart, Nicole Vogelzangs, Gérard Waeber, Peter J Wagner, Andrew Walley, G Bragi Walters, Kim L Ward, Hugh Watkins, Michael N Weedon, Sarah H Wild, Gonneke Willemsen, Jaqueline C M Witteman, John W G Yarnell, Eleftheria Zeggini, Diana Zelenika, Björn Zethelius, Guangju Zhai, Jing Hua Zhao, M Carola Zillikens, , , , Ingrid B Borecki, Ruth J F Loos, Pierre Meneton, Patrik K E Magnusson, David M Nathan, Gordon H Williams, Andrew T Hattersley, Kaisa Silander, Veikko Salomaa, George Davey Smith, Stefan R Bornstein, Peter Schwarz, Joachim Spranger, Fredrik Karpe, Alan R Shuldiner, Cyrus Cooper, George V Dedoussis, Manuel Serrano-Ríos, Andrew D Morris, Lars Lind, Lyle J Palmer, Frank B. Hu, Paul W Franks, Shah Ebrahim, Michael Marmot, W H Linda Kao, James S Pankow, Michael J Sampson, Johanna Kuusisto, Markku Laakso, Torben Hansen, Oluf Pedersen, Peter Paul Pramstaller, H Erich Wichmann, Thomas Illig, Igor Rudan, Alan F Wright, Michael Stumvoll, Harry Campbell, James F Wilson, Anders Hamsten, Richard N Bergman, Thomas A Buchanan, Francis S Collins, Karen L Mohlke, Jaakko Tuomilehto, Timo T Valle, David Altshuler, Jerome I Rotter, David S Siscovick, Brenda W J H Penninx, Dorret Boomsma, Panos Deloukas, Timothy D Spector, Timothy M Frayling, Luigi Ferrucci, Augustine Kong, Unnur Thorsteinsdottir, Kari Stefansson, Cornelia M van Duijn, Yurii S Aulchenko, Antonio Cao, Angelo Scuteri, David Schlessinger, Manuela Uda, Aimo Ruokonen, Marjo-Riitta Jarvelin, Dawn M Waterworth, Peter Vollenweider, Leena Peltonen, Vincent Mooser, Goncalo R Abecasis, Nicholas J Wareham, Robert Sladek, Philippe Froguel, Richard M Watanabe, James B Meigs, Leif Groop, Michael Boehnke, Mark I McCarthy, Jose C Florez, Inês Barroso,

ABSTRACT

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes. More... »

PAGES

105

References to SciGraph publications

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  • Journal

    TITLE

    Nature Genetics

    ISSUE

    2

    VOLUME

    42

    Author Affiliations

  • National Heart Lung and Blood Institute
  • Wellcome Centre for Human Genetics
  • Massachusetts General Hospital
  • King's College London
  • University of Michigan–Ann Arbor
  • Wellcome Sanger Institute
  • University of Washington
  • University of Oxford
  • Swiss Institute of Bioinformatics
  • Imperial College London
  • Boston University
  • deCODE Genetics (Iceland)
  • Leiden University Medical Center
  • Erasmus University Medical Center
  • University of Edinburgh
  • Medical Research Council Institute of Genetics and Molecular Medicine
  • Peninsula College of Medicine and Dentistry
  • National Institute on Aging
  • University of Oulu
  • Novo Nordisk (Denmark)
  • Ninewells Hospital
  • Johns Hopkins University
  • Harokopio University
  • University College London
  • Harvard University
  • University of Bristol
  • Hospital Clínico San Carlos
  • McGill University and Génome Québec Innovation Centre
  • Uppsala University
  • Washington University in St. Louis
  • University of Maryland, Baltimore
  • University of Lille Nord de France
  • National Human Genome Research Institute
  • Broad Institute
  • The Heart Research Institute
  • University of Western Australia
  • Icelandic Heart Association
  • University of Lausanne
  • The University of Texas Health Science Center at Houston
  • Aarhus University
  • Leipzig University
  • Cedars-Sinai Medical Center
  • University of Cagliari
  • German Institute of Human Nutrition
  • Mario Negri Institute for Pharmacological Research
  • Paris 13 University
  • TU Dresden
  • The University of Texas Southwestern Medical Center
  • Umeå University
  • German Diabetes Center - Leibniz Institute for Diabetes Research at Heinrich Heine University Düsseldorf
  • European Academy of Bozen
  • Sir Charles Gairdner Hospital
  • Folkhälsans Forskningscentrum
  • University of Copenhagen
  • National Institute for Health and Welfare
  • University of Helsinki
  • University of Exeter
  • University of Southern Denmark
  • University of California, San Francisco
  • University of Ottawa
  • Churchill Hospital
  • Second University of Naples
  • Karolinska Institute
  • University of Zagreb
  • VU University Medical Center
  • Oulu University Hospital
  • Group Health Cooperative
  • Heinrich Heine University Düsseldorf
  • University Hospital of Umeå
  • University of Cambridge
  • University of Münster
  • University of Lorraine
  • University Hospital of Lausanne
  • Queen's University Belfast
  • Medical Products Agency
  • London School of Hygiene & Tropical Medicine
  • University of Minnesota
  • Norfolk and Norwich University Hospitals NHS Foundation Trust
  • Kuopio University Hospital
  • University of Lübeck
  • Klinikum der Universität München
  • University of Split
  • University of Southern California
  • University of North Carolina at Chapel Hill
  • University of Iceland
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ng.520

    DOI

    http://dx.doi.org/10.1038/ng.520

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1004642598

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/20081858


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