A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2012-06

AUTHORS

Alisa K Manning, Marie-France Hivert, Robert A Scott, Jonna L Grimsby, Nabila Bouatia-Naji, Han Chen, Denis Rybin, Ching-Ti Liu, Lawrence F Bielak, Inga Prokopenko, Najaf Amin, Daniel Barnes, Gemma Cadby, Jouke-Jan Hottenga, Erik Ingelsson, Anne U Jackson, Toby Johnson, Stavroula Kanoni, Claes Ladenvall, Vasiliki Lagou, Jari Lahti, Cecile Lecoeur, Yongmei Liu, Maria Teresa Martinez-Larrad, May E Montasser, Pau Navarro, John R B Perry, Laura J Rasmussen-Torvik, Perttu Salo, Naveed Sattar, Dmitry Shungin, Rona J Strawbridge, Toshiko Tanaka, Cornelia M van Duijn, Ping An, Mariza de Andrade, Jeanette S Andrews, Thor Aspelund, Mustafa Atalay, Yurii Aulchenko, Beverley Balkau, Stefania Bandinelli, Jacques S Beckmann, John P Beilby, Claire Bellis, Richard N Bergman, John Blangero, Mladen Boban, Michael Boehnke, Eric Boerwinkle, Lori L Bonnycastle, Dorret I Boomsma, Ingrid B Borecki, Yvonne Böttcher, Claude Bouchard, Eric Brunner, Danijela Budimir, Harry Campbell, Olga Carlson, Peter S Chines, Robert Clarke, Francis S Collins, Arturo Corbatón-Anchuelo, David Couper, Ulf de Faire, George V Dedoussis, Panos Deloukas, Maria Dimitriou, Josephine M Egan, Gudny Eiriksdottir, Michael R Erdos, Johan G Eriksson, Elodie Eury, Luigi Ferrucci, Ian Ford, Nita G Forouhi, Caroline S Fox, Maria Grazia Franzosi, Paul W Franks, Timothy M Frayling, Philippe Froguel, Pilar Galan, Eco de Geus, Bruna Gigante, Nicole L Glazer, Anuj Goel, Leif Groop, Vilmundur Gudnason, Göran Hallmans, Anders Hamsten, Ola Hansson, Tamara B Harris, Caroline Hayward, Simon Heath, Serge Hercberg, Andrew A Hicks, Aroon Hingorani, Albert Hofman, Jennie Hui, Joseph Hung, Marjo-Riitta Jarvelin, Min A Jhun, Paul C D Johnson, J Wouter Jukema, Antti Jula, W H Kao, Jaakko Kaprio, Sharon L R Kardia, Sirkka Keinanen-Kiukaanniemi, Mika Kivimaki, Ivana Kolcic, Peter Kovacs, Meena Kumari, Johanna Kuusisto, Kirsten Ohm Kyvik, Markku Laakso, Timo Lakka, Lars Lannfelt, G Mark Lathrop, Lenore J Launer, Karin Leander, Guo Li, Lars Lind, Jaana Lindstrom, Stéphane Lobbens, Ruth J F Loos, Jian'an Luan, Valeriya Lyssenko, Reedik Mägi, Patrik K E Magnusson, Michael Marmot, Pierre Meneton, Karen L Mohlke, Vincent Mooser, Mario A Morken, Iva Miljkovic, Narisu Narisu, Jeff O'Connell, Ken K Ong, Ben A Oostra, Lyle J Palmer, Aarno Palotie, James S Pankow, John F Peden, Nancy L Pedersen, Marina Pehlic, Leena Peltonen, Brenda Penninx, Marijana Pericic, Markus Perola, Louis Perusse, Patricia A Peyser, Ozren Polasek, Peter P Pramstaller, Michael A Province, Katri Räikkönen, Rainer Rauramaa, Emil Rehnberg, Ken Rice, Jerome I Rotter, Igor Rudan, Aimo Ruokonen, Timo Saaristo, Maria Sabater-Lleal, Veikko Salomaa, David B Savage, Richa Saxena, Peter Schwarz, Udo Seedorf, Bengt Sennblad, Manuel Serrano-Rios, Alan R Shuldiner, Eric J G Sijbrands, David S Siscovick, Johannes H Smit, Kerrin S Small, Nicholas L Smith, Albert Vernon Smith, Alena Stančáková, Kathleen Stirrups, Michael Stumvoll, Yan V Sun, Amy J Swift, Anke Tönjes, Jaakko Tuomilehto, Stella Trompet, Andre G Uitterlinden, Matti Uusitupa, Max Vikström, Veronique Vitart, Marie-Claude Vohl, Benjamin F Voight, Peter Vollenweider, Gerard Waeber, Dawn M Waterworth, Hugh Watkins, Eleanor Wheeler, Elisabeth Widen, Sarah H Wild, Sara M Willems, Gonneke Willemsen, James F Wilson, Jacqueline C M Witteman, Alan F Wright, Hanieh Yaghootkar, Diana Zelenika, Tatijana Zemunik, Lina Zgaga, DIAbetes Genetics Replication And Meta-analysis Consortium, The Multiple Tissue Human Expression Resource Consortium, Nicholas J Wareham, Mark I McCarthy, Ines Barroso, Richard M Watanabe, Jose C Florez, Josée Dupuis, James B Meigs, Claudia Langenberg

ABSTRACT

Recent genome-wide association studies have described many loci implicated in type 2 diabetes (T2D) pathophysiology and β-cell dysfunction but have contributed little to the understanding of the genetic basis of insulin resistance. We hypothesized that genes implicated in insulin resistance pathways might be uncovered by accounting for differences in body mass index (BMI) and potential interactions between BMI and genetic variants. We applied a joint meta-analysis approach to test associations with fasting insulin and glucose on a genome-wide scale. We present six previously unknown loci associated with fasting insulin at P < 5 × 10(-8) in combined discovery and follow-up analyses of 52 studies comprising up to 96,496 non-diabetic individuals. Risk variants were associated with higher triglyceride and lower high-density lipoprotein (HDL) cholesterol levels, suggesting a role for these loci in insulin resistance pathways. The discovery of these loci will aid further characterization of the role of insulin resistance in T2D pathophysiology. More... »

PAGES

659

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  • Journal

    TITLE

    Nature Genetics

    ISSUE

    6

    VOLUME

    44

    Author Affiliations

  • Harvard University
  • Université de Sherbrooke
  • University of Lille Nord de France
  • Boston University
  • University of Michigan–Ann Arbor
  • Wellcome Centre for Human Genetics
  • Erasmus University Medical Center
  • Lunenfeld-Tanenbaum Research Institute
  • VU University Amsterdam
  • Karolinska Institute
  • Queen Mary University of London
  • Wellcome Sanger Institute
  • Lund University
  • University of Helsinki
  • Wake Forest University
  • Instituto de Investigación Sanitaria del Hospital Clínico San Carlos
  • University of Maryland, Baltimore
  • University of Edinburgh
  • King's College London
  • Northwestern University
  • National Institute for Health and Welfare
  • University of Glasgow
  • Umeå University
  • National Institute on Aging
  • Netherlands Consortium for Healthy Ageing
  • Washington University in St. Louis
  • Mayo Clinic
  • University of Iceland
  • University of Eastern Finland
  • University of Paris-Sud
  • Azienda Sanitaria di Firenze
  • University Hospital of Lausanne
  • Queen Elizabeth II Medical Centre
  • Texas Biomedical Research Institute
  • University of Southern California
  • University of Split
  • The University of Texas Health Science Center at Houston
  • National Human Genome Research Institute
  • Leipzig University
  • Pennington Biomedical Research Center
  • University College London
  • University of Oxford
  • University of North Carolina at Chapel Hill
  • Harokopio University
  • Icelandic Heart Association
  • National Heart Lung and Blood Institute
  • Mario Negri Institute for Pharmacological Research
  • University of Exeter
  • Imperial College London
  • National Institutes of Health
  • Centre National de Génotypage
  • European Academy of Bozen
  • University of Western Australia
  • Leiden University Medical Center
  • Johns Hopkins University
  • Oulu University Hospital
  • University of Southern Denmark
  • Kuopion Liikuntalääketieteen Tutkimuslaitos
  • Uppsala University
  • University of Washington
  • University of Tartu
  • Centre de Recherche des Cordeliers
  • GlaxoSmithKline (United States)
  • University of Pittsburgh
  • University of Minnesota
  • VU University Medical Center
  • Institute for Anthropological Research
  • Université Laval
  • Kuopio University Hospital
  • Cedars-Sinai Medical Center
  • University of Oulu
  • Pirkanmaa Hospital District
  • Institute of Metabolic Science
  • Massachusetts General Hospital
  • TU Dresden
  • University of Münster
  • Baltimore VA Medical Center
  • Amsterdam Neuroscience
  • Group Health Cooperative
  • Emory University
  • Danube University Krems
  • Broad Institute
  • University of Zagreb
  • Churchill Hospital
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ng.2274

    DOI

    http://dx.doi.org/10.1038/ng.2274

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1022356000

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/22581228


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