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

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 involving 34,840 cases and 114,981 controls, overwhelmingly of European descent. We identified ten previously unreported T2D susceptibi...

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Detalles Bibliográficos
Autores principales: 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 RB, Platou, Carl GP, 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, Uitterlinden89-, 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, 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2012
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3442244/
https://www.ncbi.nlm.nih.gov/pubmed/22885922
http://dx.doi.org/10.1038/ng.2383
Descripción
Sumario: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 involving 34,840 cases and 114,981 controls, overwhelmingly of European descent. We identified ten previously unreported T2D susceptibility loci, including two demonstrating sex-differentiated association. Genome-wide analyses of these data are consistent with a long tail of further 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 signalling and cell cycle regulation, in diabetes pathogenesis.

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