Standard
The genetic architecture of type 2 diabetes. / Fuchsberger, Christian; Flannick, Jason; Teslovich, Tanya M; Mahajan, Anubha; Agarwala, Vineeta; Gaulton, Kyle J; Ma, Clement; Fontanillas, Pierre; Moutsianas, Loukas; McCarthy, Davis J; Rivas, Manuel A; Perry, John R B; Sim, Xueling; Blackwell, Thomas W; Robertson, Neil R; Rayner, N William; Cingolani, Pablo; Locke, Adam E; Fernandez Tajes, Juan; Highland, Heather M; Dupuis, Josee; Chines, Peter S; Lindgren, Cecilia M; Hartl, Christopher; Jackson, Anne U; Chen, Han; Huyghe, Jeroen R; van de Bunt, Martijn; Pearson, Richard D; Kumar, Ashish; Müller-Nurasyid, Martina; Grarup, Niels; Stringham, Heather M; Gamazon, Eric R; Lee, Jaehoon; Chen, Yuhui; Scott, Robert A; Below, Jennifer E; Chen, Peng; Huang, Jinyan; Go, Min Jin; Stitzel, Michael L; Pasko, Dorota; Parker, Stephen C J; Varga, Tibor V; Green, Todd; Beer, Nicola L; Day-Williams, Aaron G; Ferreira, Teresa; Fingerlin, Tasha; Horikoshi, Momoko; Hu, Cheng; Huh, Iksoo; Ikram, Mohammad Kamran; Kim, Bong-Jo; Kim, Yongkang; Kim, Young Jin; Kwon, Min-Seok; Lee, Juyoung; Lee, Selyeong; Lin, Keng-Han; Maxwell, Taylor J; Nagai, Yoshihiko; Wang, Xu; Welch, Ryan P; Yoon, Joon; Zhang, Weihua; Barzilai, Nir; Voight, Benjamin F; Han, Bok-Ghee; Jenkinson, Christopher P; Kuulasmaa, Teemu; Kuusisto, Johanna; Manning, Alisa; Ng, Maggie C Y; Palmer, Nicholette D; Balkau, Beverley; Stancáková, Alena; Abboud, Hanna E; Boeing, Heiner; Giedraitis, Vilmantas; Prabhakaran, Dorairaj; Gottesman, Omri; Scott, James; Carey, Jason; Kwan, Phoenix; Grant, George; Smith, Joshua D; Neale, Benjamin M; Purcell, Shaun; Butterworth, Adam S; Howson, Joanna M M; Lee, Heung Man; Lu, Yingchang; Kwak, Soo-Heon; Zhao, Wei; Danesh, John; Lam, Vincent K L; Park, Kyong Soo; Saleheen, Danish; So, Wing Yee; Tam, Claudia H T; Afzal, Uzma; Aguilar, David; Arya, Rector; Aung, Tin; Chan, Edmund; Navarro, Carmen; Cheng, Ching-Yu; Palli, Domenico; Correa, Adolfo; Curran, Joanne E; Rybin, Denis; Farook, Vidya S; Fowler, Sharon P; Freedman, Barry I; Griswold, Michael; Hale, Daniel Esten; Hicks, Pamela J; Khor, Chiea-Chuen; Kumar, Satish; Lehne, Benjamin; Thuillier, Dorothée; Lim, Wei Yen; Liu, Jianjun; van der Schouw, Yvonne T; Loh, Marie; Musani, Solomon K; Puppala, Sobha; Scott, William R; Yengo, Loïc; Tan, Sian-Tsung; Taylor, Herman A; Thameem, Farook; Wilson, Gregory; Wong, Tien Yin; Njølstad, Pål Rasmus; Levy, Jonathan C; Mangino, Massimo; Bonnycastle, Lori L; Schwarzmayr, Thomas; Fadista, João; Surdulescu, Gabriela L; Herder, Christian; Groves, Christopher J; Wieland, Thomas; Bork-Jensen, Jette; Brandslund, Ivan; Christensen, Cramer; Koistinen, Heikki A; Doney, Alex S F; Kinnunen, Leena; Esko, Tõnu; Farmer, Andrew J; Hakaste, Liisa; Hodgkiss, Dylan; Kravic, Jasmina; Lyssenko, Valeriya; Hollensted, Mette; Jørgensen, Marit E; Jørgensen, Torben; Ladenvall, Claes; Justesen, Johanne Marie; Käräjämäki, Annemari; Kriebel, Jennifer; Rathmann, Wolfgang; Lannfelt, Lars; Lauritzen, Torsten; Narisu, Narisu; Linneberg, Allan; Melander, Olle; Milani, Lili; Neville, Matt; Orho-Melander, Marju; Qi, Lu; Qi, Qibin; Roden, Michael; Rolandsson, Olov; Swift, Amy; Rosengren, Anders H; Stirrups, Kathleen; Wood, Andrew R; Mihailov, Evelin; Blancher, Christine; Carneiro, Mauricio O; Maguire, Jared; Poplin, Ryan; Shakir, Khalid; Fennell, Timothy; DePristo, Mark; Hrabé de Angelis, Martin; Deloukas, Panos; Gjesing, Anette P.; Jun, Goo; Nilsson, Peter; Murphy, Jacquelyn; Onofrio, Robert; Thorand, Barbara; Hansen, Torben; Meisinger, Christa; Hu, Frank B; Isomaa, Bo; Karpe, Fredrik; Liang, Liming; Peters, Annette; Huth, Cornelia; O'Rahilly, Stephen P; Palmer, Colin N A; Pedersen, Oluf; Rauramaa, Rainer; Tuomilehto, Jaakko; Salomaa, Veikko; Watanabe, Richard M; Syvänen, Ann-Christine; Bergman, Richard N; Bharadwaj, Dwaipayan; Bottinger, Erwin P; Cho, Yoon Shin; Chandak, Giriraj R; Chan, Juliana C N; Chia, Kee Seng; Daly, Mark J; Ebrahim, Shah B; Langenberg, Claudia; Elliott, Paul; Jablonski, Kathleen A; Lehman, Donna M; Jia, Weiping; Ma, Ronald C W; Pollin, Toni I; Sandhu, Manjinder; Tandon, Nikhil; Froguel, Philippe; Barroso, Inês; Teo, Yik Ying; Zeggini, Eleftheria; Loos, Ruth J F; Small, Kerrin S; Ried, Janina S; DeFronzo, Ralph A; Grallert, Harald; Glaser, Benjamin; Metspalu, Andres; Wareham, Nicholas J; Walker, Mark; Banks, Eric; Gieger, Christian; Ingelsson, Erik; Im, Hae Kyung; Illig, Thomas; Franks, Paul W; Buck, Gemma; Trakalo, Joseph; Buck, David; Prokopenko, Inga; Mägi, Reedik; Lind, Lars; Farjoun, Yossi; Owen, Katharine R; Gloyn, Anna L; Strauch, Konstantin; Tuomi, Tiinamaija; Kooner, Jaspal Singh; Lee, Jong-Young; Park, Taesung; Donnelly, Peter; Morris, Andrew D; Hattersley, Andrew T; Bowden, Donald W; Collins, Francis S; Atzmon, Gil; Chambers, John C; Spector, Timothy D; Laakso, Markku; Strom, Tim M; Bell, Graeme I; Blangero, John; Duggirala, Ravindranath; Tai, E Shyong; McVean, Gilean; Hanis, Craig L; Wilson, James G; Seielstad, Mark; Frayling, Timothy M; Meigs, James B; Cox, Nancy J; Sladek, Rob; Lander, Eric S; Gabriel, Stacey; Burtt, Noël P; Mohlke, Karen L; Meitinger, Thomas; Groop, Leif; Abecasis, Goncalo; Florez, Jose C; Scott, Laura J; Morris, Andrew P; Kang, Hyun Min; Boehnke, Michael; Altshuler, David; McCarthy, Mark I.
In:
Nature, Vol. 536, No. 7614, 04.08.2016, p. 41-47.
Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
Fuchsberger, C, Flannick, J, Teslovich, TM, Mahajan, A, Agarwala, V, Gaulton, KJ, Ma, C, Fontanillas, P, Moutsianas, L, McCarthy, DJ, Rivas, MA, Perry, JRB, Sim, X, Blackwell, TW, Robertson, NR, Rayner, NW, Cingolani, P, Locke, AE, Fernandez Tajes, J, Highland, HM, Dupuis, J, Chines, PS, Lindgren, CM, Hartl, C, Jackson, AU, Chen, H, Huyghe, JR, van de Bunt, M, Pearson, RD, Kumar, A, Müller-Nurasyid, M
, Grarup, N, Stringham, HM, Gamazon, ER, Lee, J, Chen, Y, Scott, RA, Below, JE, Chen, P, Huang, J, Go, MJ, Stitzel, ML, Pasko, D, Parker, SCJ, Varga, TV, Green, T, Beer, NL, Day-Williams, AG, Ferreira, T, Fingerlin, T, Horikoshi, M, Hu, C, Huh, I, Ikram, MK, Kim, B-J, Kim, Y, Kim, YJ, Kwon, M-S, Lee, J, Lee, S, Lin, K-H, Maxwell, TJ, Nagai, Y, Wang, X, Welch, RP, Yoon, J, Zhang, W, Barzilai, N, Voight, BF, Han, B-G, Jenkinson, CP, Kuulasmaa, T, Kuusisto, J, Manning, A, Ng, MCY, Palmer, ND, Balkau, B, Stancáková, A, Abboud, HE, Boeing, H, Giedraitis, V, Prabhakaran, D, Gottesman, O, Scott, J, Carey, J, Kwan, P, Grant, G, Smith, JD, Neale, BM, Purcell, S, Butterworth, AS, Howson, JMM, Lee, HM, Lu, Y, Kwak, S-H, Zhao, W, Danesh, J, Lam, VKL, Park, KS, Saleheen, D, So, WY, Tam, CHT, Afzal, U, Aguilar, D, Arya, R, Aung, T, Chan, E, Navarro, C, Cheng, C-Y, Palli, D, Correa, A, Curran, JE, Rybin, D, Farook, VS, Fowler, SP, Freedman, BI, Griswold, M, Hale, DE, Hicks, PJ, Khor, C-C, Kumar, S, Lehne, B, Thuillier, D, Lim, WY, Liu, J, van der Schouw, YT, Loh, M, Musani, SK, Puppala, S, Scott, WR, Yengo, L, Tan, S-T, Taylor, HA, Thameem, F, Wilson, G, Wong, TY, Njølstad, PR, Levy, JC, Mangino, M, Bonnycastle, LL, Schwarzmayr, T, Fadista, J, Surdulescu, GL, Herder, C, Groves, CJ, Wieland, T, Bork-Jensen, J, Brandslund, I, Christensen, C, Koistinen, HA, Doney, ASF, Kinnunen, L, Esko, T, Farmer, AJ, Hakaste, L, Hodgkiss, D, Kravic, J, Lyssenko, V, Hollensted, M, Jørgensen, ME, Jørgensen, T, Ladenvall, C
, Justesen, JM, Käräjämäki, A, Kriebel, J, Rathmann, W, Lannfelt, L, Lauritzen, T, Narisu, N
, Linneberg, A, Melander, O, Milani, L, Neville, M, Orho-Melander, M, Qi, L, Qi, Q, Roden, M, Rolandsson, O, Swift, A, Rosengren, AH, Stirrups, K, Wood, AR, Mihailov, E, Blancher, C, Carneiro, MO, Maguire, J, Poplin, R, Shakir, K, Fennell, T, DePristo, M, Hrabé de Angelis, M, Deloukas, P, Gjesing, AP, Jun, G, Nilsson, P, Murphy, J, Onofrio, R, Thorand, B
, Hansen, T, Meisinger, C, Hu, FB, Isomaa, B, Karpe, F, Liang, L, Peters, A, Huth, C, O'Rahilly, SP, Palmer, CNA
, Pedersen, O, Rauramaa, R, Tuomilehto, J, Salomaa, V, Watanabe, RM, Syvänen, A-C, Bergman, RN, Bharadwaj, D, Bottinger, EP, Cho, YS, Chandak, GR, Chan, JCN, Chia, KS, Daly, MJ, Ebrahim, SB, Langenberg, C, Elliott, P, Jablonski, KA, Lehman, DM, Jia, W, Ma, RCW, Pollin, TI, Sandhu, M, Tandon, N, Froguel, P, Barroso, I, Teo, YY, Zeggini, E, Loos, RJF, Small, KS, Ried, JS, DeFronzo, RA, Grallert, H, Glaser, B, Metspalu, A, Wareham, NJ, Walker, M, Banks, E, Gieger, C, Ingelsson, E, Im, HK, Illig, T, Franks, PW, Buck, G, Trakalo, J, Buck, D, Prokopenko, I, Mägi, R, Lind, L, Farjoun, Y, Owen, KR, Gloyn, AL, Strauch, K, Tuomi, T, Kooner, JS, Lee, J-Y, Park, T, Donnelly, P, Morris, AD, Hattersley, AT, Bowden, DW, Collins, FS, Atzmon, G, Chambers, JC, Spector, TD, Laakso, M, Strom, TM, Bell, GI, Blangero, J, Duggirala, R, Tai, ES, McVean, G, Hanis, CL, Wilson, JG, Seielstad, M, Frayling, TM, Meigs, JB, Cox, NJ, Sladek, R, Lander, ES, Gabriel, S, Burtt, NP, Mohlke, KL, Meitinger, T, Groop, L, Abecasis, G, Florez, JC, Scott, LJ, Morris, AP, Kang, HM, Boehnke, M, Altshuler, D & McCarthy, MI 2016, '
The genetic architecture of type 2 diabetes',
Nature, vol. 536, no. 7614, pp. 41-47.
https://doi.org/10.1038/nature18642APA
Fuchsberger, C., Flannick, J., Teslovich, T. M., Mahajan, A., Agarwala, V., Gaulton, K. J., Ma, C., Fontanillas, P., Moutsianas, L., McCarthy, D. J., Rivas, M. A., Perry, J. R. B., Sim, X., Blackwell, T. W., Robertson, N. R., Rayner, N. W., Cingolani, P., Locke, A. E., Fernandez Tajes, J., ... McCarthy, M. I. (2016).
The genetic architecture of type 2 diabetes.
Nature,
536(7614), 41-47.
https://doi.org/10.1038/nature18642Vancouver
Fuchsberger C, Flannick J, Teslovich TM, Mahajan A, Agarwala V, Gaulton KJ et al.
The genetic architecture of type 2 diabetes.
Nature. 2016 Aug 4;536(7614):41-47.
https://doi.org/10.1038/nature18642Author
Fuchsberger, Christian ; Flannick, Jason ; Teslovich, Tanya M ; Mahajan, Anubha ; Agarwala, Vineeta ; Gaulton, Kyle J ; Ma, Clement ; Fontanillas, Pierre ; Moutsianas, Loukas ; McCarthy, Davis J ; Rivas, Manuel A ; Perry, John R B ; Sim, Xueling ; Blackwell, Thomas W ; Robertson, Neil R ; Rayner, N William ; Cingolani, Pablo ; Locke, Adam E ; Fernandez Tajes, Juan ; Highland, Heather M ; Dupuis, Josee ; Chines, Peter S ; Lindgren, Cecilia M ; Hartl, Christopher ; Jackson, Anne U ; Chen, Han ; Huyghe, Jeroen R ; van de Bunt, Martijn ; Pearson, Richard D ; Kumar, Ashish ; Müller-Nurasyid, Martina ; Grarup, Niels ; Stringham, Heather M ; Gamazon, Eric R ; Lee, Jaehoon ; Chen, Yuhui ; Scott, Robert A ; Below, Jennifer E ; Chen, Peng ; Huang, Jinyan ; Go, Min Jin ; Stitzel, Michael L ; Pasko, Dorota ; Parker, Stephen C J ; Varga, Tibor V ; Green, Todd ; Beer, Nicola L ; Day-Williams, Aaron G ; Ferreira, Teresa ; Fingerlin, Tasha ; Horikoshi, Momoko ; Hu, Cheng ; Huh, Iksoo ; Ikram, Mohammad Kamran ; Kim, Bong-Jo ; Kim, Yongkang ; Kim, Young Jin ; Kwon, Min-Seok ; Lee, Juyoung ; Lee, Selyeong ; Lin, Keng-Han ; Maxwell, Taylor J ; Nagai, Yoshihiko ; Wang, Xu ; Welch, Ryan P ; Yoon, Joon ; Zhang, Weihua ; Barzilai, Nir ; Voight, Benjamin F ; Han, Bok-Ghee ; Jenkinson, Christopher P ; Kuulasmaa, Teemu ; Kuusisto, Johanna ; Manning, Alisa ; Ng, Maggie C Y ; Palmer, Nicholette D ; Balkau, Beverley ; Stancáková, Alena ; Abboud, Hanna E ; Boeing, Heiner ; Giedraitis, Vilmantas ; Prabhakaran, Dorairaj ; Gottesman, Omri ; Scott, James ; Carey, Jason ; Kwan, Phoenix ; Grant, George ; Smith, Joshua D ; Neale, Benjamin M ; Purcell, Shaun ; Butterworth, Adam S ; Howson, Joanna M M ; Lee, Heung Man ; Lu, Yingchang ; Kwak, Soo-Heon ; Zhao, Wei ; Danesh, John ; Lam, Vincent K L ; Park, Kyong Soo ; Saleheen, Danish ; So, Wing Yee ; Tam, Claudia H T ; Afzal, Uzma ; Aguilar, David ; Arya, Rector ; Aung, Tin ; Chan, Edmund ; Navarro, Carmen ; Cheng, Ching-Yu ; Palli, Domenico ; Correa, Adolfo ; Curran, Joanne E ; Rybin, Denis ; Farook, Vidya S ; Fowler, Sharon P ; Freedman, Barry I ; Griswold, Michael ; Hale, Daniel Esten ; Hicks, Pamela J ; Khor, Chiea-Chuen ; Kumar, Satish ; Lehne, Benjamin ; Thuillier, Dorothée ; Lim, Wei Yen ; Liu, Jianjun ; van der Schouw, Yvonne T ; Loh, Marie ; Musani, Solomon K ; Puppala, Sobha ; Scott, William R ; Yengo, Loïc ; Tan, Sian-Tsung ; Taylor, Herman A ; Thameem, Farook ; Wilson, Gregory ; Wong, Tien Yin ; Njølstad, Pål Rasmus ; Levy, Jonathan C ; Mangino, Massimo ; Bonnycastle, Lori L ; Schwarzmayr, Thomas ; Fadista, João ; Surdulescu, Gabriela L ; Herder, Christian ; Groves, Christopher J ; Wieland, Thomas ; Bork-Jensen, Jette ; Brandslund, Ivan ; Christensen, Cramer ; Koistinen, Heikki A ; Doney, Alex S F ; Kinnunen, Leena ; Esko, Tõnu ; Farmer, Andrew J ; Hakaste, Liisa ; Hodgkiss, Dylan ; Kravic, Jasmina ; Lyssenko, Valeriya ; Hollensted, Mette ; Jørgensen, Marit E ; Jørgensen, Torben ; Ladenvall, Claes ; Justesen, Johanne Marie ; Käräjämäki, Annemari ; Kriebel, Jennifer ; Rathmann, Wolfgang ; Lannfelt, Lars ; Lauritzen, Torsten ; Narisu, Narisu ; Linneberg, Allan ; Melander, Olle ; Milani, Lili ; Neville, Matt ; Orho-Melander, Marju ; Qi, Lu ; Qi, Qibin ; Roden, Michael ; Rolandsson, Olov ; Swift, Amy ; Rosengren, Anders H ; Stirrups, Kathleen ; Wood, Andrew R ; Mihailov, Evelin ; Blancher, Christine ; Carneiro, Mauricio O ; Maguire, Jared ; Poplin, Ryan ; Shakir, Khalid ; Fennell, Timothy ; DePristo, Mark ; Hrabé de Angelis, Martin ; Deloukas, Panos ; Gjesing, Anette P. ; Jun, Goo ; Nilsson, Peter ; Murphy, Jacquelyn ; Onofrio, Robert ; Thorand, Barbara ; Hansen, Torben ; Meisinger, Christa ; Hu, Frank B ; Isomaa, Bo ; Karpe, Fredrik ; Liang, Liming ; Peters, Annette ; Huth, Cornelia ; O'Rahilly, Stephen P ; Palmer, Colin N A ; Pedersen, Oluf ; Rauramaa, Rainer ; Tuomilehto, Jaakko ; Salomaa, Veikko ; Watanabe, Richard M ; Syvänen, Ann-Christine ; Bergman, Richard N ; Bharadwaj, Dwaipayan ; Bottinger, Erwin P ; Cho, Yoon Shin ; Chandak, Giriraj R ; Chan, Juliana C N ; Chia, Kee Seng ; Daly, Mark J ; Ebrahim, Shah B ; Langenberg, Claudia ; Elliott, Paul ; Jablonski, Kathleen A ; Lehman, Donna M ; Jia, Weiping ; Ma, Ronald C W ; Pollin, Toni I ; Sandhu, Manjinder ; Tandon, Nikhil ; Froguel, Philippe ; Barroso, Inês ; Teo, Yik Ying ; Zeggini, Eleftheria ; Loos, Ruth J F ; Small, Kerrin S ; Ried, Janina S ; DeFronzo, Ralph A ; Grallert, Harald ; Glaser, Benjamin ; Metspalu, Andres ; Wareham, Nicholas J ; Walker, Mark ; Banks, Eric ; Gieger, Christian ; Ingelsson, Erik ; Im, Hae Kyung ; Illig, Thomas ; Franks, Paul W ; Buck, Gemma ; Trakalo, Joseph ; Buck, David ; Prokopenko, Inga ; Mägi, Reedik ; Lind, Lars ; Farjoun, Yossi ; Owen, Katharine R ; Gloyn, Anna L ; Strauch, Konstantin ; Tuomi, Tiinamaija ; Kooner, Jaspal Singh ; Lee, Jong-Young ; Park, Taesung ; Donnelly, Peter ; Morris, Andrew D ; Hattersley, Andrew T ; Bowden, Donald W ; Collins, Francis S ; Atzmon, Gil ; Chambers, John C ; Spector, Timothy D ; Laakso, Markku ; Strom, Tim M ; Bell, Graeme I ; Blangero, John ; Duggirala, Ravindranath ; Tai, E Shyong ; McVean, Gilean ; Hanis, Craig L ; Wilson, James G ; Seielstad, Mark ; Frayling, Timothy M ; Meigs, James B ; Cox, Nancy J ; Sladek, Rob ; Lander, Eric S ; Gabriel, Stacey ; Burtt, Noël P ; Mohlke, Karen L ; Meitinger, Thomas ; Groop, Leif ; Abecasis, Goncalo ; Florez, Jose C ; Scott, Laura J ; Morris, Andrew P ; Kang, Hyun Min ; Boehnke, Michael ; Altshuler, David ; McCarthy, Mark I. / The genetic architecture of type 2 diabetes. In: Nature. 2016 ; Vol. 536, No. 7614. pp. 41-47.
Bibtex
@article{57403a3cf4394a618f957adfd361eee8,
title = "The genetic architecture of type 2 diabetes",
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.",
keywords = "Alleles, DNA Mutational Analysis, Diabetes Mellitus, Type 2, Europe, Exome, Genetic Predisposition to Disease, Genetic Variation, Genome-Wide Association Study, Genotyping Techniques, Humans, Sample Size, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't",
author = "Christian Fuchsberger and Jason Flannick and Teslovich, {Tanya M} and Anubha Mahajan and Vineeta Agarwala and Gaulton, {Kyle J} and Clement Ma and Pierre Fontanillas and Loukas Moutsianas and McCarthy, {Davis J} and Rivas, {Manuel A} and Perry, {John R B} and Xueling Sim and Blackwell, {Thomas W} and Robertson, {Neil R} and Rayner, {N William} and Pablo Cingolani and Locke, {Adam E} and {Fernandez Tajes}, Juan and Highland, {Heather M} and Josee Dupuis and Chines, {Peter S} and Lindgren, {Cecilia M} and Christopher Hartl and Jackson, {Anne U} and Han Chen and Huyghe, {Jeroen R} and {van de Bunt}, Martijn and Pearson, {Richard D} and Ashish Kumar and Martina M{\"u}ller-Nurasyid and Niels Grarup and Stringham, {Heather M} and Gamazon, {Eric R} and Jaehoon Lee and Yuhui Chen and Scott, {Robert A} and Below, {Jennifer E} and Peng Chen and Jinyan Huang and Go, {Min Jin} and Stitzel, {Michael L} and Dorota Pasko and Parker, {Stephen C J} and Varga, {Tibor V} and Todd Green and Beer, {Nicola L} and Day-Williams, {Aaron G} and Teresa Ferreira and Tasha Fingerlin and Momoko Horikoshi and Cheng Hu and Iksoo Huh and Ikram, {Mohammad Kamran} and Bong-Jo Kim and Yongkang Kim and Kim, {Young Jin} and Min-Seok Kwon and Juyoung Lee and Selyeong Lee and Keng-Han Lin and Maxwell, {Taylor J} and Yoshihiko Nagai and Xu Wang and Welch, {Ryan P} and Joon Yoon and Weihua Zhang and Nir Barzilai and Voight, {Benjamin F} and Bok-Ghee Han and Jenkinson, {Christopher P} and Teemu Kuulasmaa and Johanna Kuusisto and Alisa Manning and Ng, {Maggie C Y} and Palmer, {Nicholette D} and Beverley Balkau and Alena Stanc{\'a}kov{\'a} and Abboud, {Hanna E} and Heiner Boeing and Vilmantas Giedraitis and Dorairaj Prabhakaran and Omri Gottesman and James Scott and Jason Carey and Phoenix Kwan and George Grant and Smith, {Joshua D} and Neale, {Benjamin M} and Shaun Purcell and Butterworth, {Adam S} and Howson, {Joanna M M} and Lee, {Heung Man} and Yingchang Lu and Soo-Heon Kwak and Wei Zhao and John Danesh and Lam, {Vincent K L} and Park, {Kyong Soo} and Danish Saleheen and So, {Wing Yee} and Tam, {Claudia H T} and Uzma Afzal and David Aguilar and Rector Arya and Tin Aung and Edmund Chan and Carmen Navarro and Ching-Yu Cheng and Domenico Palli and Adolfo Correa and Curran, {Joanne E} and Denis Rybin and Farook, {Vidya S} and Fowler, {Sharon P} and Freedman, {Barry I} and Michael Griswold and Hale, {Daniel Esten} and Hicks, {Pamela J} and Chiea-Chuen Khor and Satish Kumar and Benjamin Lehne and Doroth{\'e}e Thuillier and Lim, {Wei Yen} and Jianjun Liu and {van der Schouw}, {Yvonne T} and Marie Loh and Musani, {Solomon K} and Sobha Puppala and Scott, {William R} and Lo{\"i}c Yengo and Sian-Tsung Tan and Taylor, {Herman A} and Farook Thameem and Gregory Wilson and Wong, {Tien Yin} and Nj{\o}lstad, {P{\aa}l Rasmus} and Levy, {Jonathan C} and Massimo Mangino and Bonnycastle, {Lori L} and Thomas Schwarzmayr and Jo{\~a}o Fadista and Surdulescu, {Gabriela L} and Christian Herder and Groves, {Christopher J} and Thomas Wieland and Jette Bork-Jensen and Ivan Brandslund and Cramer Christensen and Koistinen, {Heikki A} and Doney, {Alex S F} and Leena Kinnunen and T{\~o}nu Esko and Farmer, {Andrew J} and Liisa Hakaste and Dylan Hodgkiss and Jasmina Kravic and Valeriya Lyssenko and Mette Hollensted and J{\o}rgensen, {Marit E} and Torben J{\o}rgensen and Claes Ladenvall and Justesen, {Johanne Marie} and Annemari K{\"a}r{\"a}j{\"a}m{\"a}ki and Jennifer Kriebel and Wolfgang Rathmann and Lars Lannfelt and Torsten Lauritzen and Narisu Narisu and Allan Linneberg and Olle Melander and Lili Milani and Matt Neville and Marju Orho-Melander and Lu Qi and Qibin Qi and Michael Roden and Olov Rolandsson and Amy Swift and Rosengren, {Anders H} and Kathleen Stirrups and Wood, {Andrew R} and Evelin Mihailov and Christine Blancher and Carneiro, {Mauricio O} and Jared Maguire and Ryan Poplin and Khalid Shakir and Timothy Fennell and Mark DePristo and {Hrab{\'e} de Angelis}, Martin and Panos Deloukas and Gjesing, {Anette P.} and Goo Jun and Peter Nilsson and Jacquelyn Murphy and Robert Onofrio and Barbara Thorand and Torben Hansen and Christa Meisinger and Hu, {Frank B} and Bo Isomaa and Fredrik Karpe and Liming Liang and Annette Peters and Cornelia Huth and O'Rahilly, {Stephen P} and Palmer, {Colin N A} and Oluf Pedersen and Rainer Rauramaa and Jaakko Tuomilehto and Veikko Salomaa and Watanabe, {Richard M} and Ann-Christine Syv{\"a}nen and Bergman, {Richard N} and Dwaipayan Bharadwaj 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 Claudia Langenberg and Paul Elliott and Jablonski, {Kathleen A} and Lehman, {Donna M} and Weiping Jia and Ma, {Ronald C W} and Pollin, {Toni I} and Manjinder Sandhu and Nikhil Tandon and Philippe Froguel and In{\^e}s Barroso and Teo, {Yik Ying} and Eleftheria Zeggini and Loos, {Ruth J F} and Small, {Kerrin S} and Ried, {Janina S} and DeFronzo, {Ralph A} and Harald Grallert and Benjamin Glaser and Andres Metspalu and Wareham, {Nicholas J} and Mark Walker and Eric Banks and Christian Gieger and Erik Ingelsson and Im, {Hae Kyung} and Thomas Illig and Franks, {Paul W} and Gemma Buck and Joseph Trakalo and David Buck and Inga Prokopenko and Reedik M{\"a}gi and Lars Lind and Yossi Farjoun and Owen, {Katharine R} and Gloyn, {Anna L} and Konstantin Strauch and Tiinamaija Tuomi and Kooner, {Jaspal Singh} and Jong-Young Lee and Taesung Park and Peter Donnelly and Morris, {Andrew D} and Hattersley, {Andrew T} and Bowden, {Donald W} and Collins, {Francis S} and Gil Atzmon and Chambers, {John C} and Spector, {Timothy D} and Markku Laakso and Strom, {Tim M} and Bell, {Graeme I} and John Blangero and Ravindranath Duggirala and Tai, {E Shyong} and Gilean McVean and Hanis, {Craig L} and Wilson, {James G} and Mark Seielstad and Frayling, {Timothy M} and Meigs, {James B} and Cox, {Nancy J} and Rob Sladek and Lander, {Eric S} and Stacey Gabriel and Burtt, {No{\"e}l P} and Mohlke, {Karen L} and Thomas Meitinger and Leif Groop and Goncalo Abecasis and Florez, {Jose C} and Scott, {Laura J} and Morris, {Andrew P} and Kang, {Hyun Min} and Michael Boehnke and David Altshuler and McCarthy, {Mark I}",
year = "2016",
month = aug,
day = "4",
doi = "10.1038/nature18642",
language = "English",
volume = "536",
pages = "41--47",
journal = "Nature",
issn = "0028-0836",
publisher = "nature publishing group",
number = "7614",
}
RIS
TY - JOUR
T1 - The genetic architecture of type 2 diabetes
AU - Fuchsberger, Christian
AU - Flannick, Jason
AU - Teslovich, Tanya M
AU - Mahajan, Anubha
AU - Agarwala, Vineeta
AU - Gaulton, Kyle J
AU - Ma, Clement
AU - Fontanillas, Pierre
AU - Moutsianas, Loukas
AU - McCarthy, Davis J
AU - Rivas, Manuel A
AU - Perry, John R B
AU - Sim, Xueling
AU - Blackwell, Thomas W
AU - Robertson, Neil R
AU - Rayner, N William
AU - Cingolani, Pablo
AU - Locke, Adam E
AU - Fernandez Tajes, Juan
AU - Highland, Heather M
AU - Dupuis, Josee
AU - Chines, Peter S
AU - Lindgren, Cecilia M
AU - Hartl, Christopher
AU - Jackson, Anne U
AU - Chen, Han
AU - Huyghe, Jeroen R
AU - van de Bunt, Martijn
AU - Pearson, Richard D
AU - Kumar, Ashish
AU - Müller-Nurasyid, Martina
AU - Grarup, Niels
AU - Stringham, Heather M
AU - Gamazon, Eric R
AU - Lee, Jaehoon
AU - Chen, Yuhui
AU - Scott, Robert A
AU - Below, Jennifer E
AU - Chen, Peng
AU - Huang, Jinyan
AU - Go, Min Jin
AU - Stitzel, Michael L
AU - Pasko, Dorota
AU - Parker, Stephen C J
AU - Varga, Tibor V
AU - Green, Todd
AU - Beer, Nicola L
AU - Day-Williams, Aaron G
AU - Ferreira, Teresa
AU - Fingerlin, Tasha
AU - Horikoshi, Momoko
AU - Hu, Cheng
AU - Huh, Iksoo
AU - Ikram, Mohammad Kamran
AU - Kim, Bong-Jo
AU - Kim, Yongkang
AU - Kim, Young Jin
AU - Kwon, Min-Seok
AU - Lee, Juyoung
AU - Lee, Selyeong
AU - Lin, Keng-Han
AU - Maxwell, Taylor J
AU - Nagai, Yoshihiko
AU - Wang, Xu
AU - Welch, Ryan P
AU - Yoon, Joon
AU - Zhang, Weihua
AU - Barzilai, Nir
AU - Voight, Benjamin F
AU - Han, Bok-Ghee
AU - Jenkinson, Christopher P
AU - Kuulasmaa, Teemu
AU - Kuusisto, Johanna
AU - Manning, Alisa
AU - Ng, Maggie C Y
AU - Palmer, Nicholette D
AU - Balkau, Beverley
AU - Stancáková, Alena
AU - Abboud, Hanna E
AU - Boeing, Heiner
AU - Giedraitis, Vilmantas
AU - Prabhakaran, Dorairaj
AU - Gottesman, Omri
AU - Scott, James
AU - Carey, Jason
AU - Kwan, Phoenix
AU - Grant, George
AU - Smith, Joshua D
AU - Neale, Benjamin M
AU - Purcell, Shaun
AU - Butterworth, Adam S
AU - Howson, Joanna M M
AU - Lee, Heung Man
AU - Lu, Yingchang
AU - Kwak, Soo-Heon
AU - Zhao, Wei
AU - Danesh, John
AU - Lam, Vincent K L
AU - Park, Kyong Soo
AU - Saleheen, Danish
AU - So, Wing Yee
AU - Tam, Claudia H T
AU - Afzal, Uzma
AU - Aguilar, David
AU - Arya, Rector
AU - Aung, Tin
AU - Chan, Edmund
AU - Navarro, Carmen
AU - Cheng, Ching-Yu
AU - Palli, Domenico
AU - Correa, Adolfo
AU - Curran, Joanne E
AU - Rybin, Denis
AU - Farook, Vidya S
AU - Fowler, Sharon P
AU - Freedman, Barry I
AU - Griswold, Michael
AU - Hale, Daniel Esten
AU - Hicks, Pamela J
AU - Khor, Chiea-Chuen
AU - Kumar, Satish
AU - Lehne, Benjamin
AU - Thuillier, Dorothée
AU - Lim, Wei Yen
AU - Liu, Jianjun
AU - van der Schouw, Yvonne T
AU - Loh, Marie
AU - Musani, Solomon K
AU - Puppala, Sobha
AU - Scott, William R
AU - Yengo, Loïc
AU - Tan, Sian-Tsung
AU - Taylor, Herman A
AU - Thameem, Farook
AU - Wilson, Gregory
AU - Wong, Tien Yin
AU - Njølstad, Pål Rasmus
AU - Levy, Jonathan C
AU - Mangino, Massimo
AU - Bonnycastle, Lori L
AU - Schwarzmayr, Thomas
AU - Fadista, João
AU - Surdulescu, Gabriela L
AU - Herder, Christian
AU - Groves, Christopher J
AU - Wieland, Thomas
AU - Bork-Jensen, Jette
AU - Brandslund, Ivan
AU - Christensen, Cramer
AU - Koistinen, Heikki A
AU - Doney, Alex S F
AU - Kinnunen, Leena
AU - Esko, Tõnu
AU - Farmer, Andrew J
AU - Hakaste, Liisa
AU - Hodgkiss, Dylan
AU - Kravic, Jasmina
AU - Lyssenko, Valeriya
AU - Hollensted, Mette
AU - Jørgensen, Marit E
AU - Jørgensen, Torben
AU - Ladenvall, Claes
AU - Justesen, Johanne Marie
AU - Käräjämäki, Annemari
AU - Kriebel, Jennifer
AU - Rathmann, Wolfgang
AU - Lannfelt, Lars
AU - Lauritzen, Torsten
AU - Narisu, Narisu
AU - Linneberg, Allan
AU - Melander, Olle
AU - Milani, Lili
AU - Neville, Matt
AU - Orho-Melander, Marju
AU - Qi, Lu
AU - Qi, Qibin
AU - Roden, Michael
AU - Rolandsson, Olov
AU - Swift, Amy
AU - Rosengren, Anders H
AU - Stirrups, Kathleen
AU - Wood, Andrew R
AU - Mihailov, Evelin
AU - Blancher, Christine
AU - Carneiro, Mauricio O
AU - Maguire, Jared
AU - Poplin, Ryan
AU - Shakir, Khalid
AU - Fennell, Timothy
AU - DePristo, Mark
AU - Hrabé de Angelis, Martin
AU - Deloukas, Panos
AU - Gjesing, Anette P.
AU - Jun, Goo
AU - Nilsson, Peter
AU - Murphy, Jacquelyn
AU - Onofrio, Robert
AU - Thorand, Barbara
AU - Hansen, Torben
AU - Meisinger, Christa
AU - Hu, Frank B
AU - Isomaa, Bo
AU - Karpe, Fredrik
AU - Liang, Liming
AU - Peters, Annette
AU - Huth, Cornelia
AU - O'Rahilly, Stephen P
AU - Palmer, Colin N A
AU - Pedersen, Oluf
AU - Rauramaa, Rainer
AU - Tuomilehto, Jaakko
AU - Salomaa, Veikko
AU - Watanabe, Richard M
AU - Syvänen, Ann-Christine
AU - Bergman, Richard N
AU - Bharadwaj, Dwaipayan
AU - Bottinger, Erwin P
AU - Cho, Yoon Shin
AU - Chandak, Giriraj R
AU - Chan, Juliana C N
AU - Chia, Kee Seng
AU - Daly, Mark J
AU - Ebrahim, Shah B
AU - Langenberg, Claudia
AU - Elliott, Paul
AU - Jablonski, Kathleen A
AU - Lehman, Donna M
AU - Jia, Weiping
AU - Ma, Ronald C W
AU - Pollin, Toni I
AU - Sandhu, Manjinder
AU - Tandon, Nikhil
AU - Froguel, Philippe
AU - Barroso, Inês
AU - Teo, Yik Ying
AU - Zeggini, Eleftheria
AU - Loos, Ruth J F
AU - Small, Kerrin S
AU - Ried, Janina S
AU - DeFronzo, Ralph A
AU - Grallert, Harald
AU - Glaser, Benjamin
AU - Metspalu, Andres
AU - Wareham, Nicholas J
AU - Walker, Mark
AU - Banks, Eric
AU - Gieger, Christian
AU - Ingelsson, Erik
AU - Im, Hae Kyung
AU - Illig, Thomas
AU - Franks, Paul W
AU - Buck, Gemma
AU - Trakalo, Joseph
AU - Buck, David
AU - Prokopenko, Inga
AU - Mägi, Reedik
AU - Lind, Lars
AU - Farjoun, Yossi
AU - Owen, Katharine R
AU - Gloyn, Anna L
AU - Strauch, Konstantin
AU - Tuomi, Tiinamaija
AU - Kooner, Jaspal Singh
AU - Lee, Jong-Young
AU - Park, Taesung
AU - Donnelly, Peter
AU - Morris, Andrew D
AU - Hattersley, Andrew T
AU - Bowden, Donald W
AU - Collins, Francis S
AU - Atzmon, Gil
AU - Chambers, John C
AU - Spector, Timothy D
AU - Laakso, Markku
AU - Strom, Tim M
AU - Bell, Graeme I
AU - Blangero, John
AU - Duggirala, Ravindranath
AU - Tai, E Shyong
AU - McVean, Gilean
AU - Hanis, Craig L
AU - Wilson, James G
AU - Seielstad, Mark
AU - Frayling, Timothy M
AU - Meigs, James B
AU - Cox, Nancy J
AU - Sladek, Rob
AU - Lander, Eric S
AU - Gabriel, Stacey
AU - Burtt, Noël P
AU - Mohlke, Karen L
AU - Meitinger, Thomas
AU - Groop, Leif
AU - Abecasis, Goncalo
AU - Florez, Jose C
AU - Scott, Laura J
AU - Morris, Andrew P
AU - Kang, Hyun Min
AU - Boehnke, Michael
AU - Altshuler, David
AU - McCarthy, Mark I
PY - 2016/8/4
Y1 - 2016/8/4
N2 - 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.
AB - 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.
KW - Alleles
KW - DNA Mutational Analysis
KW - Diabetes Mellitus, Type 2
KW - Europe
KW - Exome
KW - Genetic Predisposition to Disease
KW - Genetic Variation
KW - Genome-Wide Association Study
KW - Genotyping Techniques
KW - Humans
KW - Sample Size
KW - Journal Article
KW - Research Support, N.I.H., Extramural
KW - Research Support, Non-U.S. Gov't
U2 - 10.1038/nature18642
DO - 10.1038/nature18642
M3 - Journal article
C2 - 27398621
VL - 536
SP - 41
EP - 47
JO - Nature
JF - Nature
SN - 0028-0836
IS - 7614
ER -
