Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes by the DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium, Morris Andrew P, Voight Benjamin F, Teslovich Tanya M, Ferreira Teresa, Segrè Ayellet V, Steinthorsdottir Valgerdur, Strawbridge Rona J, Khan Hassan, Grallert Harald, Mahajan Anubha, Prokopenko Inga, Kang Hyun Min, Dina Christian, Esko Tonu, Fraser Ross M, Kanoni Stavroula, Kumar Ashish, Lagou Vasiliki, Langenberg Claudia, Luan Jian'an, Lindgren Cecilia M, Müller-Nurasyid Martina, Pechlivanis Sonali, Rayner N William, Scott Laura J, Wiltshire Steven, Yengo Loic, Kinnunen Leena, Rossin Elizabeth J, Raychaudhuri Soumya, Johnson Andrew D, Dimas Antigone S, Loos Ruth J F, Vedantam Sailaja, Chen Han, Florez Jose C, Fox Caroline, Liu Ching-Ti, Rybin Denis, Couper David J, Kao Wen Hong L, Li Man, Cornelis Marilyn C, Kraft Peter, Sun Qi, van Dam Rob M, Stringham Heather M, Chines Peter S, Fischer Krista, Fontanillas Pierre, Holmen Oddgeir L, Hunt Sarah E, Jackson Anne U, Kong Augustine, Lawrence Robert, Meyer Julia, Perry John R B, Platou Carl G P, Potter Simon, Rehnberg Emil, Robertson Neil, Sivapalaratnam Suthesh, Stančáková Alena, Stirrups Kathleen, Thorleifsson Gudmar, Tikkanen Emmi, Wood Andrew R, Almgren Peter, Atalay Mustafa, Benediktsson Rafn, Bonnycastle Lori L, Burtt Noël, Carey Jason, Charpentier Guillaume, Crenshaw Andrew T, Doney Alex S F, Dorkhan Mozhgan, Edkins Sarah, Emilsson Valur, Eury Elodie, Forsen Tom, Gertow Karl, Gigante Bruna, Grant George B, Groves Christopher J, Guiducci Candace, Herder Christian, Hreidarsson Astradur B, Hui Jennie, James Alan, Jonsson Anna, Rathmann Wolfgang, Klopp Norman, Kravic Jasmina, Krjutškov Kaarel, Langford Cordelia, Leander Karin, Lindholm Eero, Lobbens Stéphane, Männistö Satu, Mirza Ghazala, Mühleisen Thomas W, Musk Bill, Parkin Melissa, Rallidis Loukianos, Saramies Jouko, Sennblad Bengt, Shah Sonia, Sigurðsson Gunnar, Silveira Angela, Steinbach Gerald, Thorand Barbara, Trakalo Joseph, Veglia Fabrizio, Wennauer Roman, Winckler Wendy, Zabaneh Delilah, Campbell Harry, van Duijn Cornelia, Uitterlinden Andre G, Hofman Albert, Sijbrands Eric, Abecasis Goncalo R, Owen Katharine R, Zeggini Eleftheria, Trip Mieke D, Forouhi Nita G, Syvänen Ann-Christine, Eriksson Johan G, Peltonen Leena, Nöthen Markus M, Balkau Beverley, Palmer Colin N A, Lyssenko Valeriya, Tuomi Tiinamaija, Isomaa Bo, Hunter David J, Qi Lu, Wellcome Trust Case Control Consortium, Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) Investigators, Genetic Investigation of ANthropometric Traits (GIANT) Consortium, Asian Genetic Epidemiology Network-Type 2 Diabetes (AGEN-T2D) Consortium, South Asian Type 2 Diabetes (SAT2D) Consortium, Shuldiner Alan R, Roden Michael, Barroso Ines, Wilsgaard Tom, Beilby John, Hovingh Kees, Price Jackie F, Wilson James F, Rauramaa Rainer, Lakka Timo A, Lind Lars, Dedoussis George, Njølstad Inger, Pedersen Nancy L, Khaw Kay-Tee, Wareham Nicholas J, Keinanen-Kiukaanniemi Sirkka M, Saaristo Timo E, Korpi-Hyövälti Eeva, Saltevo Juha, Laakso Markku, Kuusisto Johanna, Metspalu Andres, Collins Francis S, Mohlke Karen L, Bergman Richard N, Tuomilehto Jaakko, Boehm Bernhard O, Gieger Christian, Hveem Kristian, Cauchi Stephane, Froguel Philippe, Baldassarre Damiano, Tremoli Elena, Humphries Steve E, Saleheen Danish, Danesh John, Ingelsson Erik, Ripatti Samuli, Salomaa Veikko, Erbel Raimund, Jöckel Karl-Heinz, Moebus Susanne, Peters Annette, Illig Thomas, de Faire Ulf, Hamsten Anders, Morris Andrew D, Donnelly Peter J, Frayling Timothy M, Hattersley Andrew T, Boerwinkle Eric, Melander Olle, Kathiresan Sekar, Nilsson Peter M, Deloukas Panos, Thorsteinsdottir Unnur, Groop Leif C, Stefansson Kari, Hu Frank, Pankow James S, Dupuis Josée, Meigs James B, Altshuler David, Boehnke Michael, McCarthy Mark I in Nature genetics (2012). PubMed

Abstract

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. Genome-wide 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.

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