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The genetic architecture of type 2 diabetes

Fuchsberger, Christian and Flannick, Jason and Teslovich, Tanya M. and Mahajan, Anubha and Agarwala, Vineeta and Gaulton, Kyle J. and Ma, Clement and Fontanillas, Pierre and Moutsianas, Loukas and McCarthy, Davis J. and Rivas, Manuel A. and Perry, John R. B. and Sim, Xueling and Blackwell, Thomas W. and Robertson, Neil R. and Rayner, N. William and Cingolani, Pablo and Locke, Adam E. and Fernandez Tajes, Juan and Highland, Heather M. and Dupuis, Josee and Chines, Peter S. and Lindgren, Cecilia M. and Hartl, Christopher and Jackson, Anne U. and Chen, Han and Huyghe, Jeroen R. and van de Bunt, Martijn and Pearson, Richard D. and Kumar, Ashish and Müller-Nurasyid, Martina and Grarup, Niels and Stringham, Heather M. and Gamazon, Eric R. and Lee, Jaehoon and Chen, Yuhui and Scott, Robert A. and Below, Jennifer E. and Chen, Peng and Huang, Jinyan and Go, Min Jin and Stitzel, Michael L. and Pasko, Dorota and Parker, Stephen C. J. and Varga, Tibor V. and Green, Todd and Beer, Nicola L. and Day-Williams, Aaron G. and Ferreira, Teresa and Fingerlin, Tasha and Horikoshi, Momoko and Hu, Cheng and Huh, Iksoo and Ikram, Mohammad Kamran and Kim, Bong-Jo and Kim, Yongkang and Kim, Young Jin and Kwon, Min-Seok and Lee, Juyoung and Lee, Selyeong and Lin, Keng-Han and Maxwell, Taylor J. and Nagai, Yoshihiko and Wang, Xu and Welch, Ryan P. and Yoon, Joon and Zhang, Weihua and Barzilai, Nir and Voight, Benjamin F. and Han, Bok-Ghee and Jenkinson, Christopher P. and Kuulasmaa, Teemu and Kuusisto, Johanna and Manning, Alisa and Ng, Maggie C. Y. and Palmer, Nicholette D. and Balkau, Beverley and Stancáková, Alena and Abboud, Hanna E. and Boeing, Heiner and Giedraitis, Vilmantas and Prabhakaran, Dorairaj and Gottesman, Omri and Scott, James and Carey, Jason and Kwan, Phoenix and Grant, George and Smith, Joshua D. and Neale, Benjamin M. and Purcell, Shaun and Butterworth, Adam S. and Howson, Joanna M. M. and Lee, Heung Man and Lu, Yingchang and Kwak, Soo-Heon and Zhao, Wei and Danesh, John and Lam, Vincent K. L. and Park, Kyong Soo and Saleheen, Danish and So, Wing Yee and Tam, Claudia H. T. and Afzal, Uzma and Aguilar, David and Arya, Rector and Aung, Tin and Chan, Edmund and Navarro, Carmen and Cheng, Ching-Yu and Palli, Domenico and Correa, Adolfo and Curran, Joanne E. and Rybin, Denis and Farook, Vidya S. and Fowler, Sharon P. and Freedman, Barry I. and Griswold, Michael and Hale, Daniel Esten and Hicks, Pamela J. and Khor, Chiea-Chuen and Kumar, Satish and Lehne, Benjamin and Thuillier, Dorothée and Lim, Wei Yen and Liu, Jianjun and van der Schouw, Yvonne T. and Loh, Marie and Musani, Solomon K. and Puppala, Sobha and Scott, William R. and Yengo, Loïc and Tan, Sian-Tsung and Taylor, Herman A. and Thameem, Farook and Wilson, Gregory and Wong, Tien Yin and Njølstad, Pål Rasmus and Levy, Jonathan C. and Mangino, Massimo and Bonnycastle, Lori L. and Schwarzmayr, Thomas and Fadista, João and Surdulescu, Gabriela L. and Herder, Christian and Groves, Christopher J. and Wieland, Thomas and Bork-Jensen, Jette and Brandslund, Ivan and Christensen, Cramer and Koistinen, Heikki A. and Doney, Alex S. F. and Kinnunen, Leena and Esko, Tõnu and Farmer, Andrew J. and Hakaste, Liisa and Hodgkiss, Dylan and Kravic, Jasmina and Lyssenko, Valeriya and Hollensted, Mette and Jørgensen, Marit E. and Jørgensen, Torben and Ladenvall, Claes and Justesen, Johanne Marie and Käräjämäki, Annemari and Kriebel, Jennifer and Rathmann, Wolfgang and Lannfelt, Lars and Lauritzen, Torsten and Narisu, Narisu and Linneberg, Allan and Melander, Olle and Milani, Lili and Neville, Matt and Orho-Melander, Marju and Qi, Lu and Qi, Qibin and Roden, Michael and Rolandsson, Olov and Swift, Amy and Rosengren, Anders H. and Stirrups, Kathleen and Wood, Andrew R. and Mihailov, Evelin and Blancher, Christine and Carneiro, Mauricio O. and Maguire, Jared and Poplin, Ryan and Shakir, Khalid and Fennell, Timothy and DePristo, Mark and Hrabé de Angelis, Martin and Deloukas, Panos and Gjesing, Anette P. and Jun, Goo and Nilsson, Peter and Murphy, Jacquelyn and Onofrio, Robert and Thorand, Barbara and Hansen, Torben and Meisinger, Christa and Hu, Frank B. and Isomaa, Bo and Karpe, Fredrik and Liang, Liming and Peters, Annette and Huth, Cornelia and O'Rahilly, Stephen P. and Palmer, Colin N. A. and Pedersen, Oluf and Rauramaa, Rainer and Tuomilehto, Jaakko and Salomaa, Veikko and Watanabe, Richard M. and Syvänen, Ann-Christine and Bergman, Richard N. and Bharadwaj, Dwaipayan and Bottinger, Erwin P. and Cho, Yoon Shin and Chandak, Giriraj R. and Chan, Juliana C. N. and Chia, Kee Seng and Daly, Mark J. and Ebrahim, Shah B. and Langenberg, Claudia and Elliott, Paul and Jablonski, Kathleen A. and Lehman, Donna M. and Jia, Weiping and Ma, Ronald C. W. and Pollin, Toni I. and Sandhu, Manjinder and Tandon, Nikhil and Froguel, Philippe and Barroso, Inês and Teo, Yik Ying and Zeggini, Eleftheria and Loos, Ruth J. F. and Small, Kerrin S. and Ried, Janina S. and DeFronzo, Ralph A. and Grallert, Harald and Glaser, Benjamin and Metspalu, Andres and Wareham, Nicholas J. and Walker, Mark and Banks, Eric and Gieger, Christian and Ingelsson, Erik and Im, Hae Kyung and Illig, Thomas and Franks, Paul W. and Buck, Gemma and Trakalo, Joseph and Buck, David and Prokopenko, Inga and Mägi, Reedik and Lind, Lars and Farjoun, Yossi and Owen, Katharine R. and Gloyn, Anna L. and Strauch, Konstantin and Tuomi, Tiinamaija and Kooner, Jaspal Singh and Lee, Jong-Young and Park, Taesung and Donnelly, Peter and Morris, Andrew D. and Hattersley, Andrew T. and Bowden, Donald W. and Collins, Francis S. and Atzmon, Gil and Chambers, John C. and Spector, Timothy D. and Laakso, Markku and Strom, Tim M. and Bell, Graeme I. and Blangero, John and Duggirala, Ravindranath and Tai, E. Shyong and McVean, Gilean and Hanis, Craig L. and Wilson, James G. and Seielstad, Mark and Frayling, Timothy M. and Meigs, James B. and Cox, Nancy J. and Sladek, Rob and Lander, Eric S. and Gabriel, Stacey and Burtt, Noël P. and Mohlke, Karen L. and Meitinger, Thomas and Groop, Leif and Abecasis, Goncalo and Florez, Jose C. and Scott, Laura J. and Morris, Andrew P. and Kang, Hyun Min and Boehnke, Michael and Altshuler, David and McCarthy, Mark I.. (2016) The genetic architecture of type 2 diabetes. Nature, 536 (7614). pp. 41-47.

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Official URL: http://edoc.unibas.ch/44592/

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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.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Epidemiology and Public Health (EPH) > Chronic Disease Epidemiology > Exposome Science (Probst-Hensch)
03 Faculty of Medicine > Departement Public Health > Sozial- und Präventivmedizin > Exposome Science (Probst-Hensch)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
UniBasel Contributors:Kumar, Ashish and Kumar, Ashish
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Macmillan
ISSN:0028-0836
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:09 Nov 2017 15:33
Deposited On:12 Dec 2016 14:34

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