The genetic architecture of type 2 diabetes

Research output: Contribution to journalJournal articleResearchpeer-review

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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 journalJournal articleResearchpeer-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/nature18642

APA

Fuchsberger, C., Flannick, J., Teslovich, T. M., Mahajan, A., Agarwala, V., Gaulton, K. J., ... McCarthy, M. I. (2016). The genetic architecture of type 2 diabetes. Nature, 536(7614), 41-47. https://doi.org/10.1038/nature18642

Vancouver

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/nature18642

Author

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 = "8",
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

VL - 536

SP - 41

EP - 47

JO - Nature

JF - Nature

SN - 0028-0836

IS - 7614

ER -

ID: 165808678