The genetic architecture of type 2 diabetes
Year: 2020
Type: article
Study design: Observational Study
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 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.
Source: UNC Libraries
DOI: 10.17615/28pw-x236
Authors: Day-Williams, Aaron G., Locke, Adam E., Deloukas, Panos, Dupuis, Josee, Jablonski, Kathleen A., Bergman, Richard N., Roden, Michael, Yengo, Loic, Danesh, John, Lee, Jong-Young, Rosengren, Anders H., Jackson, Anne U., Stančáková, Alena, Froguel, Philippe, Barzilai, Nir, Blancher, Christine, Duggirala, Ravindranath, Puppala, Sobha, Kim, Bong-Jo, Buck, David, Donnelly, Peter, McCarthy, Mark I., Liang, Liming, Metspalu, Andres, Kang, Hyun Min, Salomaa, Veikko, Smith, Joshua D., Lind, Lars, Wieland, Thomas, Hale, Daniel Esten, Ebrahim, Shah B., Barroso, Ines, Stirrups, Kathleen, Loh, Marie, Thorand, Barbara, Huh, Iksoo, Carey, Jason, Griswold, Michael, Melander, Olle, Njolstad, Pal Rasmus, Kriebel, Jennifer, Fuchsberger, Christian, Agarwala, Vineeta, Syvänen, Ann-Christine, Sladek, Rob, Tam, Claudia H.T., Levy, Jonathan C., Palli, Domenico, Linneberg, Allan, Wood, Andrew R., Rivas, Manuel A., Florez, Jose C., So, Wing Yee, Carneiro, Mauricio O., Lauritzen, Torsten, Christensen, Cramer, Loos, Ruth J.F., Maxwell, Taylor J., Seielstad, Mark, Milani, Lili, Howson, Joanna M.M., Jun, Goo, Bottinger, Erwin P., Jenkinson, Christopher P., Neville, Matt, Robertson, Neil R., Laakso, Markku, Gieger, Christian, Mihailov, Evelin, Nagai, Yoshihiko, Lee, Selyeong, Glaser, Benjamin, Gjesing, Anette P., Mangino, Massimo, Aguilar, David, Prabhakaran, Dorairaj, Frayling, Timothy M., Swift, Amy, Boehnke, Michael, Chan, Juliana C.N., Buck, Gemma, Kwak, Soo-Heon, Kravic, Jasmina, Doney, Alex S.F., Yoon, Joon, Teo, Yik Ying, Han, Bok-Ghee, Green, Todd, Wareham, Nicholas J., Horikoshi, Momoko, Lin, Keng-Han, Kwon, Min-Seok, Huth, Cornelia, Pollin, Toni I., Taylor, Herman A., Groop, Leif, Farmer, Andrew J., Lehman, Donna M., Gaulton, Kyle J., Grant, George, Tuomilehto, Jaakko, Ladenvall, Claes, Isomaa, Bo, Fingerlin, Tasha, Rybin, Denis, Manning, Alisa, Flannick, Jason, Burtt, Noël P., Bonnycastle, Lori L., Varga, Tibor V., Blackwell, Thomas W., Fennell, Timothy, Chen, Han, Bowden, Donald W., Abboud, Hanna E., Kim, Yongkang, Pasko, Dorota, Hansen, Torben, Parker, Stephen C.J., Lu, Yingchang, Lyssenko, Valeriya, Onofrio, Robert, Abecasis, Goncalo, Huang, Jinyan, Shakir, Khalid, Scott, William R., Lander, Eric S., Zeggini, Eleftheria, Käräjämäki, Annemari, Lindgren, Cecilia M., Lim, Wei Yen, Banks, Eric, Lee, Jaehoon, Scott, James, Altshuler, David, Park, Taesung, Highland, Heather M., Purcell, Shaun, Butterworth, Adam S., Boeing, Heiner, Chia, Kee Seng, Lannfelt, Lars, Thuillier, Dorothée, Meitinger, Thomas, Tajes, Juan Fernandez, Tan, Sian-Tsung, Grarup, Niels, Tai, E. Shyong, Zhao, Wei, Prokopenko, Inga, Musani, Solomon K., Narisu, Narisu, Justesen, Johanne Marie, Perry, John R.B., Farook, Vidya S., Pearson, Richard D., Illig, Thomas, Khor, Chiea-Chuen, Cho, Yoon Shin, Kooner, Jaspal Singh, Lehne, Benjamin, Small, Kerrin S., Cox, Nancy J., Sim, Xueling, Van De Bunt, Martijn, Tandon, Nikhil, Chandak, Giriraj R., Elliott, Paul, Hattersley, Andrew T., Rayner, N. William, Blangero, John, Liu, Jianjun, Herder, Christian, Bork-Jensen, Jette, Rathmann, Wolfgang, Surdulescu, Gabriela L., Farjoun, Yossi, Van Der Schouw, Yvonne T., Voight, Benjamin F., Peters, Annette, Teslovich, Tanya M., Curran, Joanne E., Hodgkiss, Dylan, Maguire, Jared, Correa, Adolfo, Fontanillas, Pierre, Müller-Nurasyid, Martina, Daly, Mark J., Afzal, Uzma, Chen, Peng, Arya, Rector, Mohlke, Karen L., Hicks, Pamela J., Kumar, Ashish, Park, Kyong Soo, Jorgensen, Torben, Meisinger, Christa, Trakalo, Joseph, Fowler, Sharon P., Esko, Tonu, Gottesman, Omri, Palmer, Colin N.A., McVean, Gilean, Nilsson, Peter, Collins, Francis S., Neale, Benjamin M., Orho-Melander, Marju, Jorgensen, Marit E., McCarthy, Davis J., Go, Min Jin, Scott, Robert A., Morris, Andrew P., Gloyn, Anna L., Hollensted, Mette, Chan, Edmund, DePristo, Mark, Lee, Heung Man, Aung, Tin, Ma, Clement, Morris, Andrew D., Kumar, Satish, Kim, Young Jin, Chines, Peter S., Fadista, Joao, Welch, Ryan P., Poplin, Ryan, Ma, Ronald C.W., Mägi, Reedik, Saleheen, Danish, Wang, Xu, Kuusisto, Johanna, Qi, Lu, Zhang, Weihua, Lam, Vincent K.L., Hanis, Craig L., Rauramaa, Rainer, Sandhu, Manjinder, DeFronzo, Ralph A., Spector, Timothy D., Kinnunen, Leena, Ferreira, Teresa, Bell, Graeme I., Rolandsson, Olov, Koistinen, Heikki A., Qi, Qibin, Palmer, Nicholette D., Wilson, Gregory, Ikram, Mohammad Kamran, Walker, Mark, Grallert, Harald, Chen, Yuhui, Ried, Janina S., Gamazon, Eric R., Bharadwaj, Dwaipayan, Brandslund, Ivan, Kwan, Phoenix, Navarro, Carmen, Tuomi, Tiinamaija, O'Rahilly, Stephen P., Moutsianas, Loukas, Pedersen, Oluf, Freedman, Barry I., Strom, Tim M., Groves, Christopher J., De Angelis, Martin Hrabé, Hu, Frank B., Cheng, Ching-Yu, Mahajan, Anubha, Balkau, Beverley, Kuulasmaa, Teemu, Im, Hae Kyung, Hu, Cheng, Owen, Katharine R., Ng, Maggie C.Y., Scott, Laura J., Franks, Paul W., Karpe, Fredrik, Below, Jennifer E., Gabriel, Stacey, Thameem, Farook, Murphy, Jacquelyn, Cingolani, Pablo, Lee, Juyoung, Langenberg, Claudia, Stitzel, Michael L., Ingelsson, Erik, Atzmon, Gil, Wong, Tien Yin, Stringham, Heather M., Schwarzmayr, Thomas, Wilson, James G., Jia, Weiping, Watanabe, Richard M., Meigs, James B., Strauch, Konstantin, Chambers, John C., Hakaste, Liisa, Hartl, Christopher, Huyghe, Jeroen R., Beer, Nicola L., Giedraitis, Vilmantas
Institution: University of North Carolina at Chapel Hill
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Funders: Bristol-Myers Squibb, Novo Nordisk
OpenAlex ID: W4300041576