The genetic architecture of type 2 diabetes View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-08

AUTHORS

Christian Fuchsberger, Jason Flannick, Tanya M. Teslovich, Anubha Mahajan, Vineeta Agarwala, Kyle J. Gaulton, Clement Ma, Pierre Fontanillas, Loukas Moutsianas, Davis J. McCarthy, Manuel A. Rivas, John R. B. Perry, Xueling Sim, Thomas W. Blackwell, Neil R. Robertson, N. William Rayner, Pablo Cingolani, Adam E. Locke, Juan Fernandez Tajes, Heather M. Highland, Josee Dupuis, Peter S. Chines, Cecilia M. Lindgren, Christopher Hartl, Anne U. Jackson, Han Chen, Jeroen R. Huyghe, Martijn van de Bunt, Richard D. Pearson, Ashish Kumar, Martina Müller-Nurasyid, Niels Grarup, Heather M. Stringham, Eric R. Gamazon, Jaehoon Lee, Yuhui Chen, Robert A. Scott, Jennifer E. Below, Peng Chen, Jinyan Huang, Min Jin Go, Michael L. Stitzel, Dorota Pasko, Stephen C. J. Parker, Tibor V. Varga, Todd Green, Nicola L. Beer, Aaron G. Day-Williams, Teresa Ferreira, Tasha Fingerlin, Momoko Horikoshi, Cheng Hu, Iksoo Huh, Mohammad Kamran Ikram, Bong-Jo Kim, Yongkang Kim, Young Jin Kim, Min-Seok Kwon, Juyoung Lee, Selyeong Lee, Keng-Han Lin, Taylor J. Maxwell, Yoshihiko Nagai, Xu Wang, Ryan P. Welch, Joon Yoon, Weihua Zhang, Nir Barzilai, Benjamin F. Voight, Bok-Ghee Han, Christopher P. Jenkinson, Teemu Kuulasmaa, Johanna Kuusisto, Alisa Manning, Maggie C. Y. Ng, Nicholette D. Palmer, Beverley Balkau, Alena Stančáková, Hanna E. Abboud, Heiner Boeing, Vilmantas Giedraitis, Dorairaj Prabhakaran, Omri Gottesman, James Scott, Jason Carey, Phoenix Kwan, George Grant, Joshua D. Smith, Benjamin M. Neale, Shaun Purcell, Adam S. Butterworth, Joanna M. M. Howson, Heung Man Lee, Yingchang Lu, Soo-Heon Kwak, Wei Zhao, John Danesh, Vincent K. L. Lam, Kyong Soo Park, Danish Saleheen, Yee So, Claudia H. T. Tam, Uzma Afzal, David Aguilar, Rector Arya, Tin Aung, Edmund Chan, Carmen Navarro, Ching-Yu Cheng, Domenico Palli, Adolfo Correa, Joanne E. Curran, Denis Rybin, Vidya S. Farook, Sharon P. Fowler, Barry I. Freedman, Michael Griswold, Daniel Esten Hale, Pamela J. Hicks, Chiea-Chuen Khor, Satish Kumar, Benjamin Lehne, Dorothée Thuillier, Wei Yen Lim, Jianjun Liu, Yvonne T. van der Schouw, Marie Loh, Solomon K. Musani, Sobha Puppala, William R. Scott, Loïc Yengo, Sian-Tsung Tan, Herman A. Taylor, Farook Thameem, Gregory Wilson, Tien Yin Wong, Pål Rasmus Njølstad, Jonathan C. Levy, Massimo Mangino, Lori L. Bonnycastle, Thomas Schwarzmayr, João Fadista, Gabriela L. Surdulescu, Christian Herder, Christopher J. Groves, Thomas Wieland, Jette Bork-Jensen, Ivan Brandslund, Cramer Christensen, Heikki A. Koistinen, Alex S. F. Doney, Leena Kinnunen, Tõnu Esko, Andrew J. Farmer, Liisa Hakaste, Dylan Hodgkiss, Jasmina Kravic, Valeriya Lyssenko, Mette Hollensted, Marit E. Jørgensen, Torben Jørgensen, Claes Ladenvall, Johanne Marie Justesen, Annemari Käräjämäki, Jennifer Kriebel, Wolfgang Rathmann, Lars Lannfelt, Torsten Lauritzen, Narisu Narisu, Allan Linneberg, Olle Melander, Lili Milani, Matt Neville, Marju Orho-Melander, Lu Qi, Qibin Qi, Michael Roden, Olov Rolandsson, Amy Swift, Anders H. Rosengren, Kathleen Stirrups, Andrew R. Wood, Evelin Mihailov, Christine Blancher, Mauricio O. Carneiro, Jared Maguire, Ryan Poplin, Khalid Shakir, Timothy Fennell, Mark DePristo, Martin Hrabé de Angelis, Panos Deloukas, Anette P. Gjesing, Goo Jun, Peter Nilsson, Jacquelyn Murphy, Robert Onofrio, Barbara Thorand, Torben Hansen, Christa Meisinger, Frank B. Hu, Bo Isomaa, Fredrik Karpe, Liming Liang, Annette Peters, Cornelia Huth, Stephen P. O’Rahilly, Colin N. A. Palmer, Oluf Pedersen, Rainer Rauramaa, Jaakko Tuomilehto, Veikko Salomaa, Richard M. Watanabe, Ann-Christine Syvänen, Richard N. Bergman, Dwaipayan Bharadwaj, Erwin P. Bottinger, Yoon Shin Cho, Giriraj R. Chandak, Juliana C. N. Chan, Kee Seng Chia, Mark J. Daly, Shah B. Ebrahim, Claudia Langenberg, Paul Elliott, Kathleen A. Jablonski, Donna M. Lehman, Weiping Jia, Ronald C. W., Toni I. Pollin, Manjinder Sandhu, Nikhil Tandon, Philippe Froguel, Inês Barroso, Yik Ying Teo, Eleftheria Zeggini, Ruth J. F. Loos, Kerrin S. Small, Janina S. Ried, Ralph A. DeFronzo, Harald Grallert, Benjamin Glaser, Andres Metspalu, Nicholas J. Wareham, Mark Walker, Eric Banks, Christian Gieger, Erik Ingelsson, Hae Kyung Im, Thomas Illig, Paul W. Franks, Gemma Buck, Joseph Trakalo, David Buck, Inga Prokopenko, Reedik Mägi, Lars Lind, Yossi Farjoun, Katharine R. Owen, Anna L. Gloyn, Konstantin Strauch, Tiinamaija Tuomi, Jaspal Singh Kooner, Jong-Young Lee, Taesung Park, Peter Donnelly, Andrew D. Morris, Andrew T. Hattersley, Donald W. Bowden, Francis S. Collins, Gil Atzmon, John C. Chambers, Timothy D. Spector, Markku Laakso, Tim M. Strom, Graeme I. Bell, John Blangero, Ravindranath Duggirala, E. Shyong Tai, Gilean McVean, Craig L. Hanis, James G. Wilson, Mark Seielstad, Timothy M. Frayling, James B. Meigs, Nancy J. Cox, Rob Sladek, Eric S. Lander, Stacey Gabriel, Noël P. Burtt, Karen L. Mohlke, Thomas Meitinger, Leif Groop, Goncalo Abecasis, Jose C. Florez, Laura J. Scott, Andrew P. Morris, Hyun Min Kang, Michael Boehnke, David Altshuler, Mark I. McCarthy

ABSTRACT

The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of the heritability of this disease. Here, to test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole-genome sequencing in 2,657 European individuals with and without diabetes, and exome sequencing in 12,940 individuals from five ancestry groups. To increase statistical power, we expanded the sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes. More... »

PAGES

41

Journal

TITLE

Nature

ISSUE

7614

VOLUME

536

Author Affiliations

  • European Academy of Bozen
  • Massachusetts General Hospital
  • University of Michigan–Ann Arbor
  • Wellcome Centre for Human Genetics
  • Massachusetts Institute of Technology
  • Broad Institute
  • University of Oxford
  • King's College London
  • Wellcome Sanger Institute
  • McGill University and Génome Québec Innovation Centre
  • The University of Texas Health Science Center at Houston
  • National Heart Lung and Blood Institute
  • National Human Genome Research Institute
  • Harvard University
  • German Centre for Cardiovascular Research
  • University of Copenhagen
  • Seoul National University
  • Institute of Metabolic Science
  • National University of Singapore
  • Korea National Institute of Health
  • Jackson Laboratory
  • University of Exeter
  • Lund University
  • University of Colorado Anschutz Medical Campus
  • Duke NUS Graduate Medical School
  • McGill University Health Centre
  • Ealing Hospital NHS Trust
  • Albert Einstein College of Medicine
  • University of Pennsylvania
  • South Texas Veterans Health Care System
  • University of Eastern Finland
  • Kuopio University Hospital
  • Wake Forest University
  • Centre for research in epidemiology and population health
  • The University of Texas Health Science Center at San Antonio
  • German Institute of Human Nutrition
  • Uppsala University
  • Centre for Chronic Disease Control
  • Icahn School of Medicine at Mount Sinai
  • Imperial College London
  • University of Washington
  • University of Cambridge
  • Chinese University of Hong Kong
  • Center for Non-Communicable Diseases
  • Baylor College of Medicine
  • University of Murcia
  • Istituto per lo Studio e la Prevenzione Oncologica
  • University of Mississippi Medical Center
  • The University of Texas Rio Grande Valley
  • Boston University
  • Texas Biomedical Research Institute
  • Genome Institute of Singapore
  • Lille 1 University
  • University Medical Center Utrecht
  • Agency for Science, Technology and Research
  • Jackson State University
  • Haukeland University Hospital
  • German Center for Diabetes Research
  • Vejle Sygehus
  • Helsinki University Central Hospital
  • Ninewells Hospital
  • National Institute for Health and Welfare
  • Boston Children's Hospital
  • University of Helsinki
  • Steno Diabetes Center
  • Aalborg University
  • Vaasa Central Hospital
  • Helmholtz Zentrum München
  • German Diabetes Center - Leibniz Institute for Diabetes Research at Heinrich Heine University Düsseldorf
  • Aarhus University
  • University of Tartu
  • NIHR Oxford Musculoskeletal Biomedical Research Unit
  • Brigham and Women's Hospital
  • Heinrich Heine University Düsseldorf
  • Umeå University
  • Technical University Munich
  • King Abdulaziz University
  • University of Southern Denmark
  • Folkhälsans Forskningscentrum
  • Kuopion Liikuntalääketieteen Tutkimuslaitos
  • University of Southern California
  • Institute of Genomics and Integrative Biology
  • Hallym University
  • Centre for Cellular and Molecular Biology
  • George Washington University
  • University of Maryland, Baltimore
  • All India Institute of Medical Sciences
  • Hadassah Medical Center
  • Newcastle University
  • Hannover Medical School
  • Ludwig Maximilian University of Munich
  • University of Edinburgh
  • University of Haifa
  • Blood Systems Research Institute
  • McGill University
  • University of North Carolina at Chapel Hill
  • University of Liverpool
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nature18642

    DOI

    http://dx.doi.org/10.1038/nature18642

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1036558635

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/27398621


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