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Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility

Title: Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility
Authors: Mahajan, A
Go, MJ
Zhang, W
Below, JE
Gaulton, KJ
Ferreira, T
Horikoshi, M
Johnson, AD
Ng, MCY
Prokopenko, I
Saleheen, D
Wang, X
Zeggini, E
Abecasis, GR
Adair, LS
Almgren, P
Atalay, M
Aung, T
Baldassarre, D
Balkau, B
Bao, Y
Barnett, AH
Barroso, I
Basit, A
Been, LF
Beilby, J
Bell, GI
Benediktsson, R
Bergman, RN
Boehm, BO
Boerwinkle, E
Bonnycastle, LL
Burtt, N
Cai, Q
Campbell, H
Carey, J
Cauchi, S
Caulfield, M
Chan, JCN
Chang, L-C
Chang, T-J
Chang, Y-C
Charpentier, G
Chen, C-H
Chen, H
Chen, Y-T
Chia, K-S
Chidambaram, M
Chines, PS
Cho, NH
Cho, YM
Chuang, L-M
Collins, FS
Cornelis, MC
Couper, DJ
Crenshaw, AT
Van Dam, RM
Danesh, J
Das, D
De Faire, U
Dedoussis, G
Deloukas, P
Dimas, AS
Dina, C
Doney, ASF
Donnelly, PJ
Dorkhan, M
Van Duijn, C
Dupuis, J
Edkins, S
Elliott, P
Emilsson, V
Erbel, R
Eriksson, JG
Escobedo, J
Esko, T
Eury, E
Florez, JC
Fontanillas, P
Forouhi, NG
Forsen, T
Fox, C
Fraser, RM
Frayling, TM
Froguel, P
Frossard, P
Gao, Y
Gertow, K
Gieger, C
Gigante, B
Grallert, H
Grant, GB
Groop, LC
Groves, CJ
Grundberg, E
Guiducci, C
Hamsten, A
Han, B-G
Hara, K
Hassanali, N
Hattersley, AT
Hayward, C
Hedman, AK
Herder, C
Hofman, A
Holmen, OL
Hovingh, K
Hreidarsson, AB
Hu, C
Hu, FB
Hui, J
Humphries, SE
Hunt, SE
Hunter, DJ
Hveem, K
Hydrie, ZI
Ikegami, H
Illig, T
Ingelsson, E
Islam, M
Isomaa, B
Jackson, AU
Jafar, T
James, A
Jia, W
Joeckel, K-H
Jonsson, A
Jowett, JBM
Kadowaki, T
Kang, HM
Kanoni, S
Kao, WHL
Kathiresan, S
Kato, N
Katulanda, P
Keinanen-Kiukaanniemi, SM
Kelly, AM
Khan, H
Khaw, K-T
Khor, C-C
Kim, H-L
Kim, S
Kim, YJ
Kinnunen, L
Klopp, N
Kong, A
Korpi-Hyovalti, E
Kowlessur, S
Kraft, P
Kravic, J
Kristensen, MM
Krithika, S
Kumar, A
Kumate, J
Kuusisto, J
Kwak, SH
Laakso, M
Lagou, V
Lakka, TA
Langenberg, C
Langford, C
Lawrence, R
Leander, K
Lee, J-M
Lee, NR
Li, M
Li, X
Li, Y
Liang, J
Liju, S
Lim, W-Y
Lind, L
Lindgren, CM
Lindholm, E
Liu, C-T
Liu, JJ
Lobbens, S
Long, J
Loos, RJF
Lu, W
Luan, J
Lyssenko, V
Ma, RCW
Maeda, S
Maegi, R
Mannisto, S
Matthews, DR
Meigs, JB
Melander, O
Metspalu, A
Meyer, J
Mirza, G
Mihailov, E
Moebus, S
Mohan, V
Mohlke, KL
Morris, AD
Muehleisen, TW
Mueller-Nurasyid, M
Musk, B
Nakamura, J
Nakashima, E
Navarro, P
Peng-Keat, N
Nica, AC
Nilsson, PM
Njolstad, I
Noethen, MM
Ohnaka, K
Ong, TH
Owen, KR
Palmer, CNA
Pankow, JS
Park, KS
Parkin, M
Pechlivanis, S
Pedersen, NL
Peltonen, L
Perry, JRB
Peters, A
Pinidiyapathirage, JM
Platou, CGP
Potter, S
Price, JF
Qi, L
Radha, V
Rallidis, L
Rasheed, A
Rathmann, W
Rauramaa, R
Raychaudhuri, S
Rayner, NW
Rees, SD
Rehnberg, E
Ripatti, S
Robertson, N
Roden, M
Rossin, EJ
Rudan, I
Rybin, D
Saaristo, TE
Salomaa, V
Saltevo, J
Samuel, M
Sanghera, DK
Saramies, J
Scott, J
Scott, LJ
Scott, RA
Segre, AV
Sehmi, J
Sennblad, B
Shah, N
Shah, S
Shera, AS
Shu, XO
Shuldiner, AR
Sigurdsson, G
Sijbrands, E
Silveira, A
Sim, X
Sivapalaratnam, S
Small, KS
So, WY
Stancakova, A
Stefansson, K
Steinbach, G
Steinthorsdottir, V
Stirrups, K
Strawbridge, RJ
Stringham, HM
Sun, Q
Suo, C
Syvanen, A-C
Takayanagi, R
Takeuchi, F
Tay, WT
Teslovich, TM
Thorand, B
Thorleifsson, G
Thorsteinsdottir, U
Tikkanen, E
Trakalo, J
Tremoli, E
Trip, MD
Tsai, FJ
Tuomi, T
Tuomilehto, J
Uitterlinden, AG
Valladares-Salgado, A
Vedantam, S
Veglia, F
Voight, BF
Wang, C
Wareham, NJ
Wennauer, R
Wickremasinghe, AR
Wilsgaard, T
Wilson, JF
Wiltshire, S
Winckler, W
Wong, TY
Wood, AR
Wu, J-Y
Wu, Y
Yamamoto, K
Yamauchi, T
Yang, M
Yengo, L
Yokota, M
Young, R
Zabaneh, D
Zhang, F
Zhang, R
Zheng, W
Zimmet, PZ
Altshuler, D
Bowden, DW
Cho, YS
Cox, NJ
Cruz, M
Hanis, CL
Kooner, J
Lee, J-Y
Seielstad, M
Teo, YY
Boehnke, M
Parra, EJ
Chambers, JC
Tai, ES
McCarthy, MI
Morris, AP
Item Type: Journal Article
Abstract: To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We observed a significant excess in the directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls of European ancestry, we identified seven new T2D susceptibility loci. Furthermore, we observed considerable improvements in the fine-mapping resolution of common variant association signals at several T2D susceptibility loci. These observations highlight the benefits of trans-ethnic GWAS for the discovery and characterization of complex trait loci and emphasize an exciting opportunity to extend insight into the genetic architecture and pathogenesis of human diseases across populations of diverse ancestry.
Issue Date: 1-Mar-2014
Date of Acceptance: 17-Jan-2014
URI: http://hdl.handle.net/10044/1/18309
DOI: 10.1038/ng.2897
ISSN: 1061-4036
Publisher: Nature Research
Start Page: 234
End Page: 244
Journal / Book Title: Nature Genetics
Volume: 46
Issue: 3
Copyright Statement: © 2014 Nature America, Inc. All rights reserved.
Sponsor/Funder: Medical Research Council (MRC)
Medical Research Council (MRC)
National Institute for Health Research
Funder's Grant Number: G0801056
G1002084
NF-SI-0611-10136
Keywords: Science & Technology
Life Sciences & Biomedicine
Genetics & Heredity
ASSOCIATION ANALYSES
GLUCOSE-HOMEOSTASIS
LOCI
VARIANTS
INDIVIDUALS
CHROMATIN
IDENTIFY
Alleles
Asian Continental Ancestry Group
Case-Control Studies
Diabetes Mellitus, Type 2
European Continental Ancestry Group
Genetic Predisposition to Disease
Genome-Wide Association Study
Hispanic Americans
Humans
Polymorphism, Single Nucleotide
Risk Factors
DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium
Asian Genetic Epidemiology Network Type 2 Diabetes (AGEN-T2D) Consortium
South Asian Type 2 Diabetes (SAT2D) Consortium
Mexican American Type 2 Diabetes (MAT2D) Consortium
Type 2 Diabetes Genetic Exploration by Nex-generation sequencing in muylti-Ethnic Samples (T2D-GENES) Consortium
Humans
Diabetes Mellitus, Type 2
Genetic Predisposition to Disease
Risk Factors
Case-Control Studies
Polymorphism, Single Nucleotide
Alleles
Asian Continental Ancestry Group
European Continental Ancestry Group
Hispanic Americans
Genome-Wide Association Study
Science & Technology
Life Sciences & Biomedicine
Genetics & Heredity
ASSOCIATION ANALYSES
GLUCOSE-HOMEOSTASIS
LOCI
VARIANTS
INDIVIDUALS
CHROMATIN
IDENTIFY
06 Biological Sciences
11 Medical and Health Sciences
Developmental Biology
Publication Status: Published
Online Publication Date: 2014-02-09
Appears in Collections:Faculty of Medicine
School of Public Health