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

description: 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 heritability. 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 Europeans with and without diabetes, and exome sequencing in a total of 12,940 subjects from five ancestral groups. To increase statistical power, we expanded 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 a major role for lower-frequency variants in predisposition to type 2 diabetes.