The genetic architecture of type 2 diabetes.

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Title: The genetic architecture of type 2 diabetes.
Author(s): Fuchsberger, C
Flannick, J
Teslovich, TM
Mahajan, A
Agarwala, V
Gaulton, KJ
Ma, C
Fontanillas, P
Moutsianas, L
McCarthy, DJ
Rivas, MA
Wood, AR
Mihailov, E
Blancher, C
Carneiro, MO
Maguire, J
Poplin, R
Shakir, K
Fennell, T
DePristo, M
Highland, HM
So, WY
Hrabé de Angelis, M
Deloukas, P
Gjesing, AP
Jun, G
Nilsson, P
Murphy, J
Onofrio, R
Thorand, B
Hansen, T
Meisinger, C
Tam, CH
Dupuis, J
Hu, FB
Isomaa, B
Karpe, F
Liang, L
Peters, A
Huth, C
O'Rahilly, SP
Palmer, CN
Pedersen, O
Afzal, U
Rauramaa, R
Chines, PS
Tuomilehto, J
Salomaa, V
Watanabe, RM
Syvänen, AC
Bergman, RN
Bharadwaj, D
Bottinger, EP
Cho, YS
Aguilar, D
Chandak, GR
Chan, JC
Lindgren, CM
Chia, KS
Daly, MJ
Ebrahim, SB
Langenberg, C
Elliott, P
Jablonski, KA
Lehman, DM
Arya, R
Jia, W
Ma, RC
Pollin, TI
Hartl, C
Sandhu, M
Tandon, N
Froguel, P
Barroso, I
Teo, YY
Zeggini, E
Aung, T
Loos, RJ
Small, KS
Ried, JS
DeFronzo, RA
Jackson, AU
Grallert, H
Glaser, B
Metspalu, A
Wareham, NJ
Walker, M
Chan, E
Banks, E
Gieger, C
Ingelsson, E
Im, HK
Illig, T
Chen, H
Franks, PW
Buck, G
Trakalo, J
Buck, D
Navarro, C
Prokopenko, I
Mägi, R
Lind, L
Farjoun, Y
Owen, KR
Gloyn, AL
Huyghe, JR
Strauch, K
Tuomi, T
Kooner, JS
Cheng, CY
Lee, JY
Park, T
Donnelly, P
Morris, AD
Hattersley, AT
Bowden, DW
Collins, FS
Van de Bunt, M
Atzmon, G
Chambers, JC
Palli, D
Spector, TD
Laakso, M
Strom, TM
Bell, GI
Blangero, J
Duggirala, R
Tai, ES
McVean, G
Pearson, RD
Hanis, CL
Perry, JR
Wilson, JG
Seielstad, M
Frayling, TM
Meigs, JB
Cox, NJ
Sladek, R
Lander, ES
Gabriel, S
Burtt, NP
Kumar, A
Correa, A
Mohlke, KL
Meitinger, T
Groop, L
Abecasis, G
Florez, JC
Scott, LJ
Morris, AP
Kang, HM
Boehnke, M
Altshuler, D
Curran, JE
Müller-Nurasyid, M
McCarthy, MI
Grarup, N
Stringham, HM
Gamazon, ER
Lee, J
Chen, Y
Scott, RA
Below, JE
Chen, P
Rybin, D
Huang, J
Go, MJ
Stitzel, ML
Pasko, D
Parker, SC
Varga, TV
Green, T
Beer, NL
Day-Williams, AG
Ferreira, T
Farook, VS
Fingerlin, T
Horikoshi, M
Hu, C
Huh, I
Ikram, MK
Kim, BJ
Kim, Y
Kim, YJ
Kwon, MS
Lee, J
Fowler, SP
Lee, S
Lin, KH
Maxwell, TJ
Nagai, Y
Wang, X
Welch, RP
Yoon, J
Zhang, W
Barzilai, N
Voight, BF
Freedman, BI
Han, BG
Jenkinson, CP
Kuulasmaa, T
Kuusisto, J
Manning, A
Ng, MC
Palmer, ND
Balkau, B
Stančáková, A
Abboud, HE
Griswold, M
Boeing, H
Giedraitis, V
Prabhakaran, D
Gottesman, O
Scott, J
Carey, J
Kwan, P
Grant, G
Smith, JD
Neale, BM
Hale, DE
Purcell, S
Butterworth, AS
Howson, JM
Lee, HM
Lu, Y
Kwak, SH
Zhao, W
Danesh, J
Lam, VK
Park, KS
Hicks, PJ
Saleheen, D
Khor, CC
Sim, X
Kumar, S
Lehne, B
Thuillier, D
Lim, WY
Liu, J
Van der Schouw, YT
Loh, M
Musani, SK
Puppala, S
Scott, WR
Blackwell, TW
Yengo, L
Tan, ST
Taylor, HA
Thameem, F
Wilson, G
Wong, TY
Njølstad, PR
Levy, JC
Mangino, M
Bonnycastle, LL
Robertson, NR
Schwarzmayr, T
Fadista, J
Surdulescu, GL
Herder, C
Groves, CJ
Wieland, T
Bork-Jensen, J
Brandslund, I
Christensen, C
Koistinen, HA
Rayner, NW
Doney, AS
Kinnunen, L
Esko, T
Farmer, AJ
Hakaste, L
Hodgkiss, D
Kravic, J
Lyssenko, V
Hollensted, M
Jørgensen, ME
Cingolani, P
Jørgensen, T
Ladenvall, C
Justesen, JM
Käräjämäki, A
Kriebel, J
Rathmann, W
Lannfelt, L
Lauritzen, T
Narisu, N
Linneberg, A
Locke, AE
Melander, O
Milani, L
Neville, M
Orho-Melander, M
Qi, L
Qi, Q
Roden, M
Rolandsson, O
Swift, A
Rosengren, AH
Tajes, JF
Stirrups, K
Item Type: Journal Article
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.
Publication Date: 11-Jul-2016
Date of Acceptance: 12-Jun-2016
URI: http://hdl.handle.net/10044/1/39454
DOI: https://dx.doi.org/10.1038/nature18642
ISSN: 0028-0836
Publisher: Nature Publishing Group
Start Page: 41
End Page: 47
Journal / Book Title: Nature
Volume: 536
Sponsor/Funder: British Heart Foundation
Wellcome Trust
Medical Research Council (MRC)
Funder's Grant Number: SP/04/02
084723/Z/08/Z
G0601966
Copyright Statement: Copyright © 2016, Rights Managed by Nature Publishing Group
Keywords: General Science & Technology
MD Multidisciplinary
Publication Status: Published
Appears in Collections:Faculty of Medicine
Epidemiology, Public Health and Primary Care



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