Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2012-09

AUTHORS

Robert A Scott, Vasiliki Lagou, Ryan P Welch, Eleanor Wheeler, May E Montasser, Jian’an Luan, Reedik Mägi, Rona J Strawbridge, Emil Rehnberg, Stefan Gustafsson, Stavroula Kanoni, Laura J Rasmussen-Torvik, Loïc Yengo, Cecile Lecoeur, Dmitry Shungin, Serena Sanna, Carlo Sidore, Paul C D Johnson, J Wouter Jukema, Toby Johnson, Anubha Mahajan, Niek Verweij, Gudmar Thorleifsson, Jouke-Jan Hottenga, Sonia Shah, Albert V Smith, Bengt Sennblad, Christian Gieger, Perttu Salo, Markus Perola, Nicholas J Timpson, David M Evans, Beate St Pourcain, Ying Wu, Jeanette S Andrews, Jennie Hui, Lawrence F Bielak, Wei Zhao, Momoko Horikoshi, Pau Navarro, Aaron Isaacs, Jeffrey R O’Connell, Kathleen Stirrups, Veronique Vitart, Caroline Hayward, Tönu Esko, Evelin Mihailov, Ross M Fraser, Tove Fall, Benjamin F Voight, Soumya Raychaudhuri, Han Chen, Cecilia M Lindgren, Andrew P Morris, Nigel W Rayner, Neil Robertson, Denis Rybin, Ching-Ti Liu, Jacques S Beckmann, Sara M Willems, Peter S Chines, Anne U Jackson, Hyun Min Kang, Heather M Stringham, Kijoung Song, Toshiko Tanaka, John F Peden, Anuj Goel, Andrew A Hicks, Ping An, Martina Müller-Nurasyid, Anders Franco-Cereceda, Lasse Folkersen, Letizia Marullo, Hanneke Jansen, Albertine J Oldehinkel, Marcel Bruinenberg, James S Pankow, Kari E North, Nita G Forouhi, Ruth J F Loos, Sarah Edkins, Tibor V Varga, Göran Hallmans, Heikki Oksa, Mulas Antonella, Ramaiah Nagaraja, Stella Trompet, Ian Ford, Stephan J L Bakker, Augustine Kong, Meena Kumari, Bruna Gigante, Christian Herder, Patricia B Munroe, Mark Caulfield, Jula Antti, Massimo Mangino, Kerrin Small, Iva Miljkovic, Yongmei Liu, Mustafa Atalay, Wieland Kiess, Alan L James, Fernando Rivadeneira, Andre G Uitterlinden, Colin N A Palmer, Alex S F Doney, Gonneke Willemsen, Johannes H Smit, Susan Campbell, Ozren Polasek, Lori L Bonnycastle, Serge Hercberg, Maria Dimitriou, Jennifer L Bolton, Gerard R Fowkes, Peter Kovacs, Jaana Lindström, Tatijana Zemunik, Stefania Bandinelli, Sarah H Wild, Hanneke V Basart, Wolfgang Rathmann, Harald Grallert, , Winfried Maerz, Marcus E Kleber, Bernhard O Boehm, Annette Peters, Peter P Pramstaller, Michael A Province, Ingrid B Borecki, Nicholas D Hastie, Igor Rudan, Harry Campbell, Hugh Watkins, Martin Farrall, Michael Stumvoll, Luigi Ferrucci, Dawn M Waterworth, Richard N Bergman, Francis S Collins, Jaakko Tuomilehto, Richard M Watanabe, Eco J C de Geus, Brenda W Penninx, Albert Hofman, Ben A Oostra, Bruce M Psaty, Peter Vollenweider, James F Wilson, Alan F Wright, G Kees Hovingh, Andres Metspalu, Matti Uusitupa, Patrik K E Magnusson, Kirsten O Kyvik, Jaakko Kaprio, Jackie F Price, George V Dedoussis, Panos Deloukas, Pierre Meneton, Lars Lind, Michael Boehnke, Alan R Shuldiner, Cornelia M van Duijn, Andrew D Morris, Anke Toenjes, Patricia A Peyser, John P Beilby, Antje Körner, Johanna Kuusisto, Markku Laakso, Stefan R Bornstein, Peter E H Schwarz, Timo A Lakka, Rainer Rauramaa, Linda S Adair, George Davey Smith, Tim D Spector, Thomas Illig, Ulf de Faire, Anders Hamsten, Vilmundur Gudnason, Mika Kivimaki, Aroon Hingorani, Sirkka M Keinanen-Kiukaanniemi, Timo E Saaristo, Dorret I Boomsma, Kari Stefansson, Pim van der Harst, Josée Dupuis, Nancy L Pedersen, Naveed Sattar, Tamara B Harris, Francesco Cucca, Samuli Ripatti, Veikko Salomaa, Karen L Mohlke, Beverley Balkau, Philippe Froguel, Anneli Pouta, Marjo-Riitta Jarvelin, Nicholas J Wareham, Nabila Bouatia-Naji, Mark I McCarthy, Paul W Franks, James B Meigs, Tanya M Teslovich, Jose C Florez, Claudia Langenberg, Erik Ingelsson, Inga Prokopenko, Inês Barroso

ABSTRACT

Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have increased the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes risk (q < 0.05). Loci influencing fasting insulin concentration showed association with lipid levels and fat distribution, suggesting impact on insulin resistance. Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations. This conclusion is supported by an excess of directionally consistent and nominally significant signals between discovery and follow-up studies. Functional analysis of these newly discovered loci will further improve our understanding of glycemic control. More... »

PAGES

991

Journal

TITLE

Nature Genetics

ISSUE

9

VOLUME

44

Author Affiliations

  • University of Oxford
  • University of Michigan–Ann Arbor
  • Wellcome Sanger Institute
  • University of Tartu
  • Karolinska University Hospital
  • Karolinska Institute
  • Northwestern University
  • Pasteur Institute of Lille
  • Umeå University
  • Institute of Genetic and Biomedical Research
  • University of Sassari
  • University of Glasgow
  • Leiden University Medical Center
  • Queen Mary University of London
  • University Medical Center Groningen
  • deCODE Genetics (Iceland)
  • EMGO Institute for Health and Care Research
  • University College London
  • University of Iceland
  • Helmholtz Zentrum München
  • National Institute for Health and Welfare
  • University of Helsinki
  • University of Bristol
  • University of North Carolina at Chapel Hill
  • Wake Forest University
  • Pathwest Laboratory Medicine
  • Erasmus University Medical Center
  • University of Edinburgh
  • University of Pennsylvania
  • Brigham and Women's Hospital
  • Boston University
  • Hôpital Orthopédique de la Suisse Romande
  • National Human Genome Research Institute
  • GlaxoSmithKline (United States)
  • National Institute on Aging
  • Illumina (United Kingdom)
  • Washington University in St. Louis
  • Ludwig Maximilian University of Munich
  • University of Ferrara
  • University of Minnesota
  • University Hospital of Umeå
  • Pirkanmaa Hospital District
  • German Diabetes Center - Leibniz Institute for Diabetes Research at Heinrich Heine University Düsseldorf
  • King's College London
  • University of Pittsburgh
  • University of Eastern Finland
  • Leipzig University
  • Sir Charles Gairdner Hospital
  • University of Dundee
  • VU University Medical Center
  • University of Split
  • Paris 13 University
  • Harokopio University
  • Azienda Sanitaria di Firenze
  • Academic Medical Center
  • Heidelberg University
  • University Hospital Ulm
  • University of Lübeck
  • University of Southern California
  • Danube University Krems
  • Netherlands Consortium for Healthy Ageing
  • University of Washington
  • University of Lausanne
  • Kuopio University Hospital
  • Centre de Recherche des Cordeliers
  • Uppsala University
  • Baltimore VA Medical Center
  • TU Dresden
  • Kuopion Liikuntalääketieteen Tutkimuslaitos
  • University of North Carolina System
  • Hannover Medical School
  • Oulu University Hospital
  • Finnish Diabetes Association
  • National Heart Lung and Blood Institute
  • University of Paris-Sud
  • Imperial College London
  • University of Oulu
  • Paris Cardiovascular Research Center
  • Churchill Hospital
  • Harvard University
  • Broad Institute
  • Institute of Metabolic Science
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ng.2385

    DOI

    http://dx.doi.org/10.1038/ng.2385

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1010034001

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/22885924


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