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The genetic architecture of type 2 diabetes
- Source :
- Nature, 536(7614), 41-+. Nature Publishing Group, 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, Tajes, J F, Highland, H M, Dupuis, J, Chines, P S, Lindgren, C M, Hartl, C, Jackson, A U, Chen, H, Huyghe, J R, van de Bunt, M, Pearson, R D, Kumar, A, Müller-Nurasyid, M, Grarup, N, Stringham, H M, Gamazon, E R, Lee, J, Chen, Y, Scott, R A, Below, J E, Chen, P, Huang, J, Go, M J, Stitzel, M L, Pasko, D, Parker, S C J, Varga, T V, Green, T, Beer, N L, Day-Williams, A G, Ferreira, T, Fingerlin, T, Horikoshi, M, Hu, C, Huh, I, Ikram, M K, Kim, B-J, Kim, Y, Kim, Y J, Kwon, M-S, Lee, J, Lee, S, Lin, K-H, Maxwell, T J, Nagai, Y, Wang, X, Welch, R P, Yoon, J, Zhang, W, Barzilai, N, Voight, B F, Han, B-G, Jenkinson, C P, Kuulasmaa, T, Kuusisto, J, Manning, A, Ng, M C Y, Palmer, N D, Balkau, B, Stančáková, A, Abboud, H E, Boeing, H, Giedraitis, V, Prabhakaran, D, Gottesman, O, Scott, J, Carey, J, Kwan, P, Grant, G, Smith, J D, Neale, B M, Purcell, S, Butterworth, A S, Howson, J M M, Lee, H M, Lu, Y, Kwak, S-H, Zhao, W, Danesh, J, Lam, V K L, Park, K S, Saleheen, D, So, W Y, Tam, C H T, Afzal, U, Aguilar, D, Arya, R, Aung, T, Chan, E, Navarro, C, Cheng, C-Y, Palli, D, Correa, A, Curran, J E, Rybin, D, Farook, V S, Fowler, S P, Freedman, B I, Griswold, M, Hale, D E, Hicks, P J, Khor, C-C, Kumar, S, Lehne, B, Thuillier, D, Lim, W Y, Liu, J, van der Schouw, Y T, Loh, M, Musani, S K, Puppala, S, Scott, W R, Yengo, L, Tan, S-T, Taylor, H A, Thameem, F, Wilson, G, Wong, T Y, Njølstad, P R, Levy, J C, Mangino, M, Bonnycastle, L L, Schwarzmayr, T, Fadista, J, Surdulescu, G L, Herder, C, Groves, C J, Wieland, T, Bork-Jensen, J, Brandslund, I, Christensen, C, Koistinen, H A, Doney, A S F, Kinnunen, L, Esko, T, Farmer, A J, Hakaste, L, Hodgkiss, D, Kravic, J, Lyssenko, V, Hollensted, M, Jørgensen, M E, Jørgensen, T, Ladenvall, C, Justesen, J M, 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, A H, Stirrups, K, Wood, A R, Mihailov, E, Blancher, C, Carneiro, M O, Maguire, J, Poplin, R, Shakir, K, Fennell, T, DePristo, M, Hrabé de Angelis, M, Deloukas, P, Gjesing, A P, Jun, G, Nilsson, P, Murphy, J, Onofrio, R, Thorand, B, Hansen, T, Meisinger, C, Hu, F B, Isomaa, B, Karpe, F, Liang, L, Peters, A, Huth, C, O'Rahilly, S P, Palmer, C N A, Pedersen, O, Rauramaa, R, Tuomilehto, J, Salomaa, V, Watanabe, R M, Syvänen, A-C, Bergman, R N, Bharadwaj, D, Bottinger, E P, Cho, Y S, Chandak, G R, Chan, J C N, Chia, K S, Daly, M J, Ebrahim, S B, Langenberg, C, Elliott, P, Jablonski, K A, Lehman, D M, Jia, W, Ma, R C W, Pollin, T I, Sandhu, M, Tandon, N, Froguel, P, Barroso, I, Teo, Y Y, Zeggini, E, Loos, R J F, Small, K S, Ried, J S, DeFronzo, R A, Grallert, H, Glaser, B, Metspalu, A, Wareham, N J, Walker, M, Banks, E, Gieger, C, Ingelsson, E, Im, H K, Illig, T, Franks, P W, Buck, G, Trakalo, J, Buck, D, Prokopenko, I, Mägi, R, Lind, L, Farjoun, Y, Owen, K R, Gloyn, A L, Strauch, K, Tuomi, T, Kooner, J S, Lee, J-Y, Park, T, Donnelly, P, Morris, A D, Hattersley, A T, Bowden, D W, Collins, F S, Atzmon, G, Chambers, J C, Spector, T D, Laakso, M, Strom, T M, Bell, G I, Blangero, J, Duggirala, R, Tai, E S, McVean, G, Hanis, C L, Wilson, J G, Seielstad, M, Frayling, T M, Meigs, J B, Cox, N J, Sladek, R, Lander, E S, Gabriel, S, Burtt, N P, Mohlke, K L, Meitinger, T, Groop, L, Abecasis, G, Florez, J C, Scott, L J, Morris, A P, Kang, H M, Boehnke, M, Altshuler, D & McCarthy, M I 2016, ' The genetic architecture of type 2 diabetes ', Nature, vol. 536, no. 7614, pp. 41-47 . https://doi.org/10.1038/nature18642, NATURE, Repositorio Institucional de la Consejería de Sanidad de la Comunidad de Madrid, Consejería de Sanidad de la Comunidad de Madrid, 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, Tajes, J F, Highland, H M, Dupuis, J, Chines, P S, Lindgren, C M, Hartl, C, Jackson, A U, Chen, H, Huyghe, J R, van de Bunt, M, Pearson, R D, Kumar, A, Mueller-Nurasyid, M, Grarup, N, Stringham, H M, Gamazon, E R, Lee, J, Chen, Y, Scott, R A, Below, J E, Chen, P-M, Huang, J, Go, M J, Stitzel, M L, Pasko, D, Parker, S C J, Varga, T V, Green, T, Beer, N L, Day-Williams, A G, Ferreira, T, Fingerlin, T, Horikoshi, M, Hu, C, Huh, I, Ikram, M K, Kim, B-J, Kim, Y, Kim, Y J, Kwon, M-S, Lee, J, Lee, S, Lin, K-H, Maxwell, T J, Nagai, Y, Wang, X-G, Welch, R P, Yoon, J, Zhang, W, Barzilai, N, Voight, B F, Han, B-G, Jenkinson, C P, Kuulasmaa, T, Kuusisto, J, Manning, A K, Ng, M C Y, Palmer, N D, Balkau, B, Stancáková, A, Abboud, H E, Boeing, H, Giedraitis, V, Prabhakaran, D, Gottesman, O, Scott, J, Carey, J, Kwan, P, Grant, G, Smith, J D, Neale, B M, Purcell, S, Butterworth, A S, Howson, J M M, Lee, H M, Lu, Y, Kwak, S-H, Zhao, W, Danesh, J, Lam, V K L, Park, K S, Saleheen, D, So, W-Y, Tam, C H T, Afzal, U, Aguilar, D, Arya, R, Aung, T, Chan, E, Navarro, C, Cheng, C-Y, Palli, D, Correa, A, Curran, J E, Rybin, D, Farook, V S, Fowler, S P, Freedman, B I, Griswold, M E, Hale, D E, Hicks, P J, Khor, C-C, Kumar, S, Lehne, B, Thuillier, D, Lim, W Y, Liu, J, van der Schouw, Y T, Loh, M, Musani, S K, Puppala, S, Scott, W R, Yengo, L, Tan, S-T, Taylor, H A, Thameem, F, Wilson, G A, Wong, T Y, Njolstad, P R, Levy, J C, Mangino, M, Bonnycastle, L L, Schwarzmayr, T, Fadista, J, Surdulescu, G L, Herder, C, Groves, C J, Wieland, T, Bork-Jensen, J, Brandslund, I, Christensen, C, Koistinen, H A, Doney, A S F, Kinnunen, L, Esko, T, Farmer, A J, Hakaste, L, Hodgkiss, D, Kravic, J, Lyssenko, V, Hollensted, M, Jorgensen, M E, Jorgensen, T, Ladenvall, C, Justesen, J M, Karajamaki, A, Kriebel, J, Rathmann, W, Lannfelt, L, Lauritzen, T, Narisu, N, Linneberg, A, Melander, O, Milani, L, Neville, M J, Orho-Melander, M, Qi, L, Qi, Q, Roden, M, Rolandsson, O, Swift, A J, Rosengren, A H, Stirrups, K, Wood, A R, Mihailov, E, Blancher, C, Carneiro, M O, Maguire, J, Poplin, R, Shakir, K, Fennell, T, DePristo, M, de Angelis, M H, Deloukas, P, Gjesing, A P, Jun, G, Nilsson, P, Murphy, J, Onofrio, R, Thorand, B, Hansen, T, Meisinger, C, Hu, F B, Isomaa, B, Karpe, F, Liang, L, Peters, A, Huth, C, O'Rahilly, S P, Palmer, C N A, Pedersen, O, Rauramaa, R, Tuomilehto, J, Salomaa, V, Watanabe, R M, Syvanen, A-C, Bergman, R N, Bharadwaj, D, Bottinger, E P, Cho, Y S, Chandak, G R, Chan, J C N, Chia, K S, Daly, M J, Ebrahim, S B, Langenberg, C, Elliott, P, Jablonski, K A, Lehman, D M, Jia, W, Ma, R C W, Pollin, T I, Sandhu, M S, Tandon, N, Froguel, P, Barroso, I, Teo, Y Y, Zeggini, E, Loos, R J F, Small, K S, Ried, J S, DeFronzo, R A, Grallert, H, Glaser, B, Metspalu, A, Wareham, N J, Walker, M, Banks, E, Gieger, C, Ingelsson, E, Im, H K, Illig, T, Franks, P W, Buck, G, Trakalo, J, Buck, D, Prokopenko, I, Magi, R, Lind, L, Farjoun, Y, Owen, K R, Gloyn, A L, Strauch, K, Tuomi, T, Kooner, J S, Lee, J-Y, Park, T, Donnelly, P, Morris, A D, Hattersley, A T, Bowden, D W, Collins, F S, Atzmon, G, Chambers, J C, Spector, T D, Laakso, M, Strom, T M, Bell, G I, Blangero, J, Duggirala, R, Tai, E S, McVean, G, Hanis, C L, Wilson, J G, Seielstad, M, Frayling, T M, Meigs, J B, Cox, N J, Sladek, R, Lander, E S, Gabriel, S, Burtt, N P, Mohlke, K L, Meitinger, T, Groop, L, Abecasis, G R, Florez, J C, Scott, L J, Morris, A P, Kang, H M, Boehnke, M, Altshuler, D & McCarthy, M I 2016, ' The genetic architecture of type 2 diabetes ', Nature Genetics, vol. 536, no. 7614, pp. 41-+ . https://doi.org/10.1038/nature18642, 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, Highland, H M, Dupuis, J, Chines, P S, Lindgren, C M, Hartl, C, Jackson, A U, Chen, H, Huyghe, J R, van de Bunt, M, Pearson, R D, Kumar, A, Müller-Nurasyid, M, Grarup, N, Stringham, H M, Gamazon, E R, Lee, J, Chen, Y, Scott, R A, Below, J E, Chen, P, Huang, J, Go, M J, Stitzel, M L, Pasko, D, Parker, S C J, Varga, T V, Green, T, Beer, N L, Day-Williams, A G, Ferreira, T, Fingerlin, T, Horikoshi, M, Hu, C, Huh, I, Ikram, M K, Kim, B-J, Kim, Y, Kim, Y J, Kwon, M-S, Lee, J, Lee, S, Lin, K-H, Maxwell, T J, Nagai, Y, Wang, X, Welch, R P, Yoon, J, Zhang, W, Barzilai, N, Voight, B F, Han, B-G, Jenkinson, C P, Kuulasmaa, T, Kuusisto, J, Manning, A, Ng, M C Y, Palmer, N D, Balkau, B, Stancáková, A, Abboud, H E, Boeing, H, Giedraitis, V, Prabhakaran, D, Gottesman, O, Scott, J, Carey, J, Kwan, P, Grant, G, Smith, J D, Neale, B M, Purcell, S, Butterworth, A S, Howson, J M M, Lee, H M, Lu, Y, Kwak, S-H, Zhao, W, Danesh, J, Lam, V K L, Park, K S, Saleheen, D, So, W Y, Tam, C H T, Afzal, U, Aguilar, D, Arya, R, Aung, T, Chan, E, Navarro, C, Cheng, C-Y, Palli, D, Correa, A, Curran, J E, Rybin, D, Farook, V S, Fowler, S P, Freedman, B I, Griswold, M, Hale, D E, Hicks, P J, Khor, C-C, Kumar, S, Lehne, B, Thuillier, D, Lim, W Y, Liu, J, van der Schouw, Y T, Loh, M, Musani, S K, Puppala, S, Scott, W R, Yengo, L, Tan, S-T, Taylor, H A, Thameem, F, Wilson, G, Wong, T Y, Njølstad, P R, Levy, J C, Mangino, M, Bonnycastle, L L, Schwarzmayr, T, Fadista, J, Surdulescu, G L, Herder, C, Groves, C J, Wieland, T, Bork-Jensen, J, Brandslund, I, Christensen, C, Koistinen, H A, Doney, A S F, Kinnunen, L, Esko, T, Farmer, A J, Hakaste, L, Hodgkiss, D, Kravic, J, Lyssenko, V, Hollensted, M, Jørgensen, M E, Jørgensen, T, Ladenvall, C, Justesen, J M, 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, A H, Stirrups, K, Wood, A R, Mihailov, E, Blancher, C, Carneiro, M O, Maguire, J, Poplin, R, Shakir, K, Fennell, T, DePristo, M, Hrabé de Angelis, M, Deloukas, P, Gjesing, A P, Jun, G, Nilsson, P, Murphy, J, Onofrio, R, Thorand, B, Hansen, T, Meisinger, C, Hu, F B, Isomaa, B, Karpe, F, Liang, L, Peters, A, Huth, C, O'Rahilly, S P, Palmer, C N A, Pedersen, O, Rauramaa, R, Tuomilehto, J, Salomaa, V, Watanabe, R M, Syvänen, A-C, Bergman, R N, Bharadwaj, D, Bottinger, E P, Cho, Y S, Chandak, G R, Chan, J C N, Chia, K S, Daly, M J, Ebrahim, S B, Langenberg, C, Elliott, P, Jablonski, K A, Lehman, D M, Jia, W, Ma, R C W, Pollin, T I, Sandhu, M, Tandon, N, Froguel, P, Barroso, I, Teo, Y Y, Zeggini, E, Loos, R J F, Small, K S, Ried, J S, DeFronzo, R A, Grallert, H, Glaser, B, Metspalu, A, Wareham, N J, Walker, M, Banks, E, Gieger, C, Ingelsson, E, Im, H K, Illig, T, Franks, P W, Buck, G, Trakalo, J, Buck, D, Prokopenko, I, Mägi, R, Lind, L, Farjoun, Y, Owen, K R, Gloyn, A L, Strauch, K, Tuomi, T, Kooner, J S, Lee, J-Y, Park, T, Donnelly, P, Morris, A D, Hattersley, A T, Bowden, D W, Collins, F S, Atzmon, G, Chambers, J C, Spector, T D, Laakso, M, Strom, T M, Bell, G I, Blangero, J, Duggirala, R, Tai, E S, McVean, G, Hanis, C L, Wilson, J G, Seielstad, M, Frayling, T M, Meigs, J B, Cox, N J, Sladek, R, Lander, E S, Gabriel, S, Burtt, N P, Mohlke, K L, Meitinger, T, Groop, L, Abecasis, G, Florez, J C, Scott, L J, Morris, A P, Kang, H M, Boehnke, M, Altshuler, D & McCarthy, M I 2016, ' The genetic architecture of type 2 diabetes ', Nature, vol. 536, no. 7614, pp. 41-47 . https://doi.org/10.1038/nature18642, PMC, Nature, 536(7614), 41. Nature Publishing Group, Nature, Nature, 536(7614), 41-47. Nature Publishing Group
- Publication Year :
- 2016
-
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.
- Subjects :
- 0301 basic medicine
PROTEIN INTERACTION NETWORKS
SUSCEPTIBILITY LOCI
Genotyping Techniques
General Science & Technology
DNA Mutational Analysis
SEQUENCING ASSOCIATION
030209 endocrinology & metabolism
Genome-wide association study
Biology
Research Support
N.I.H
03 medical and health sciences
0302 clinical medicine
Research Support, N.I.H., Extramural
SDG 3 - Good Health and Well-being
MD Multidisciplinary
Genetic predisposition
Journal Article
Humans
Exome
Genetic Predisposition to Disease
GENOME-WIDE ASSOCIATION
Non-U.S. Gov't
Exome sequencing
Alleles
Genetic association
Genetics
RISK
Multidisciplinary
HERITABILITY
Research Support, Non-U.S. Gov't
COMPLEX TRAITS
Extramural
Genetic Variation
Genetic architecture
HUMAN-DISEASE
Europe
030104 developmental biology
Diabetes Mellitus, Type 2
RARE VARIANTS
Sample Size
LOW-FREQUENCY
Imputation (genetics)
Common disease-common variant
Genome-Wide Association Study
Subjects
Details
- Language :
- English
- ISSN :
- 00280836
- Volume :
- 536
- Issue :
- 7614
- Database :
- OpenAIRE
- Journal :
- Nature
- Accession number :
- edsair.doi.dedup.....1508fe3fd38042ce3a7e808bc55bf202