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

Andrew P. Morris, Benjamin F. Voight, Tanya M. Teslovich, Teresa Ferreira, Ayellet V. Segre, 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 LuanCecilia M. Lindgren, Martina Mueller-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 Stancakova, Kathleen Stirrups, Gudmar Thorleifsson, Emmi Tikkanen, Andrew R. Wood, Peter Almgren, Mustafa Atalay, Rafn Benediktsson, Lori L. Bonnycastle, Noel 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 Krjutskov, Cordelia Langford, Karin Leander, Eero Lindholm, Stephane Lobbens, Satu Mannisto, Ghazala Mirza, Thomas W. Muehleisen, Bill Musk, Melissa Parkin, Loukianos Rallidis, Jouko Saramies, Bengt Sennblad, Sonia Shah, Gunnar Sigurdsson, 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 Syvanen, Johan G. Eriksson, Leena Peltonen, Markus M. Noethen, 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 Njolstad, Nancy L. Pedersen, Kay-Tee Khaw, Nicholas J. Wareham, Sirkka M. Keinanen-Kiukaanniemi, Timo E. Saaristo, Eeva Korpi-Hyovalti, 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 Joeckel, 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 Nilsson, Panos Deloukas, Unnur Thorsteinsdottir, Leif Groop, Kari Stefansson, Frank Hu, James S. Pankow, Josee Dupuis, James B. Meigs, David Altshuler, Michael Boehnke, Mark I. McCarthy

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review

Sammanfattning

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. Genomewide 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.
Originalspråkengelska
Sidor (från-till)981
TidskriftNature Genetics
Volym44
Nummer9
DOI
StatusPublished - 2012

Ämnesklassifikation (UKÄ)

  • Endokrinologi och diabetes
  • Annan klinisk medicin
  • Kardiologi och kardiovaskulära sjukdomar

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