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Genome-Wide Trans-Ancestry Meta-Analysis Provides Insight into the Genetic Architecture of Type 2 Diabetes Susceptibility

Citation

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 Next-generation sequencing in multi-Ethnic Samples (T2D-GENES CONSORTIUM) Consortium,; Mahajan, Anubha; Go, Min Jin; Zhang, Weihua; Below, Jennifer E.; & Gaulton, Kyle J., et al. (2014). Genome-Wide Trans-Ancestry Meta-Analysis Provides Insight into the Genetic Architecture of Type 2 Diabetes Susceptibility. Nature Genetics, 46(3), 234-244. PMCID: PMC3969612

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.

URL

http://dx.doi.org/10.1038/ng.2897

Reference Type

Journal Article

Year Published

2014

Journal Title

Nature Genetics

Author(s)

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 Next-generation sequencing in multi-Ethnic Samples (T2D-GENES CONSORTIUM) Consortium,
Mahajan, Anubha
Go, Min Jin
Zhang, Weihua
Below, Jennifer E.
Gaulton, Kyle J.
Ferreira, Teresa
Horikoshi, Momoko
Johnson, Andrew D.
Ng, Maggie C. Y.
Prokopenko, Inga
Saleheen, Danish
Wang, Xu
Zeggini, Eleftheria
Abecasis, Gonçalo R.
Adair, Linda S.
Almgren, Peter
Atalay, Mustafa
Aung, Tin
Baldassarre, Damiano
Balkau, Beverley
Bao, Yuqian
Barnett, Anthony H.
Barroso, Ines
Basit, Abdul
Been, Latonya F.
Beilby, John
Bell, Graeme I.
Benediktsson, Rafn
Bergman, Richard N.
Boehm, Bernhard O.
Boerwinkle, Eric A.
Bonnycastle, Lori L.
Burtt, Noel P.
Cai, Qiuyin
Campbell, Harry
Carey, Jason
Cauchi, Stephane
Caulfield, Mark J.
Chan, Juliana C. N.
Chang, Li-Ching
Chang, Tien-Jyun
Chang, Yi-Cheng
Charpentier, Guillaume
Chen, Chien-Hsiun
Chen, Han
Chen, Yuan-Tsong
Chia, Kee-Seng
Chidambaram, Manickam
Chines, Peter S.
Cho, Nam H.
Cho, Young Min
Chuang, Lee-Ming
Collins, Francis S.
Cornelis, Marilyn C.
Couper, David J.
Crenshaw, Andrew T.
van Dam, Rob M.
Danesh, John
Das, Debashish
de Faire, Ulf
Dedoussis, George
Deloukas, Panos
Dimas, Antigone S.
Dina, Christian
Doney, Alex S. F.
Donnelly, Peter J.
Dorkhan, Mozhgan
van Duijn, Cornelia M.
Dupuis, Josee
Edkins, Sarah
Elliott, Paul
Emilsson, Valur
Erbel, Raimund
Eriksson, Johan G.
Escobedo, Jorge
Esko, Tonu
Eury, Elodie
Florez, Jose C.
Fontanillas, Pierre
Forouhi, Nita G.
Forsen, Tom
Fox, Caroline S.
Fraser, Ross M.
Frayling, Timothy M.
Froguel, Philippe
Frossard, Philippe
Gao, Yu-Tang
Gertow, Karl
Gieger, Christian
Gigante, Bruna
Grallert, Harald
Grant, George B.
Groop, Leif C.
Groves, Christopher J.
Grundberg, Elin
Guiducci, Candace
Hamsten, Anders
Han, Bok-Ghee
Hara, Kazuo
Hassanali, Neelam
Hattersley, Andrew T.
Hayward, Caroline
Hedman, Asa K.
Herder, Christian
Hofman, Albert
Holmen, Oddgeir L.
Hovingh, G. Kees
Hreidarsson, Astradur B.
Hu, Cheng
Hu, Frank B.
Hui, Jennie
Humphries, Steve E.
Hunt, Sarah E.
Hunter, David J.
Hveem, Kristian
Hydrie, Zafar I.
Ikegami, Hiroshi
Illig, Thomas
Ingelsson, Erik
Islam, Muhammed
Isomaa, Bo
Jackson, Anne U.
Jafar, Tazeen
James, Alan L.
Jia, Weiping
Jockel, Karl-Heinz
Jonsson, Anna E.
Jowett, Jeremy B. M.
Kadowaki, Takashi
Kang, Hyun Min
Kanoni, Stavroula
Kao, Wen Hong Linda
Kathiresan, Sekar
Kato, Norihiro
Katulanda, Prasad
Keinanen-Kiukaanniemi, Sirkka M.
Kelly, Ann M.
Khan, Hassan
Khaw, Kay-Tee
Khor, Chiea Chuen
Kim, Hyung-Lae
Kim, Sangsoo
Kim, Young Jin
Kinnunen, Leena
Klopp, Norman
Kong, Augustine
Korpi-Hyovalti, Eeva
Kowlessur, Sudhir
Kraft, Peter
Kravic, Jasmina
Kristensen, Malene M.
Krithika, S.
Kumar, Ashish
Kumate, Jesus
Kuusisto, Johanna
Kwak, Soo Heon
Laakso, Markku
Lagou, Vasiliki
Lakka, Timo A.
Langenberg, Claudia
Langford, Cordelia
Lawrence, Robert S.
Leander, Karin
Lee, Jeannette
Lee, Nanette R.
Li, Man
Li, Xinzhong
Li, Yun
Liang, Junbin
Liju, Samuel
Lim, Wei-Yen
Lind, Lars
Lindgren, Cecilia M.
Lindholm, Eero
Liu, Ching-Ti
Liu, Jianjun
Lobbens, Stephane
Long, Jirong
Loos, Ruth J. F.
Lu, Wei
Luan, Jian'an
Lyssenko, Valeriya
Ma, Ronald C. W.
Maeda, Shiro
Magi, Reedik
Mannisto, Satu
Matthews, David R.
Meigs, James B.
Melander, Olle
Metspalu, Andres
Meyer, Julia
Mirza, Ghazala
Mihailov, Evelin
Moebus, Susanne
Mohan, Viswanathan
Mohlke, Karen L.
Morris, Andrew D.
Muhleisen, Thomas W.
Muller-Nurasyid, Martina
Musk, Arthur W.
Nakamura, Jiro
Nakashima, Eitaro
Navarro, Pau
Ng, Peng-Keat
Nica, Alexandra C.
Nilsson, Peter M.
Njolstad, Inger
Nothen, Markus M.
Ohnaka, Keizo
Ong, Rick Twee-Hee
Owen, Katharine R.
Palmer, Colin N. A.
Pankow, James S.
Park, Kyong Soo
Parkin, Melissa
Pechlivanis, Sonali
Pedersen, Nancy L.
Peltonen, Leena
Perry, John R. B.
Peters, Annette
Pinidiyapathirage, Janani M.
Platou, Carl G. P.
Potter, Simon
Price, Jackie F.
Qi, Lu
Radha, Venkatesan
Rallidis, Loukianos S.
Rasheed, Asif
Rathmann, Wolfgang
Rauramaa, Rainer
Raychaudhuri, Soumya
Rayner, Nigel W.
Rees, Simon D.
Rehnberg, Emil
Ripatti, Samuli
Robertson, Neil R.
Roden, Michael
Rossin, Elizabeth J.
Rudan, Igor
Rybin, Denis
Saaristo, Timo E.
Salomaa, Veikko
Saltevo, Juha
Samuel, Maria
Sanghera, Dharambir K.
Saramies, Jouko
Scott, James
Scott, Laura J.
Scott, Robert A.
Segre, Ayellet V.
Sehmi, Joban
Sennblad, Bengt
Shah, Nabi
Shah, Sonia
Shera, A. Samad
Shu, Xiao -u
Shuldiner, Alan R.
Sigursson, Gunnar
Sijbrands, Eric
Silveira, Angela
Sim, Xueling
Sivapalaratnam, Suthesh
Small, Kerrin S.
So, Wing Yee
Stancakova, Alena
Stefansson, Kari
Steinbach, Gerald
Steinthorsdottir, Valgerdur
Stirrups, Kathleen E.
Strawbridge, Rona J.
Stringham, Heather M.
Sun, Qi
Suo, Chen
Syvanen, Ann-Christine
Takayanagi, Ryoichi
Takeuchi, Fumihiko
Tay, Wan Ting
Teslovich, Tanya M.
Thorand, Barbara
Thorleifsson, Gudmar
Thorsteinsdottir, Unnur
Tikkanen, Emmi
Trakalo, Joseph
Tremoli, Elena
Trip, Mieke D.
Tsai, Fuu-Jen
Tuomi, Tiinamaija
Tuomilehto, Jaakko
Uitterlinden, Andre G.
Valladares-Salgado, Adan
Vedantam, Sailaja
Veglia, Fabrizio
Voight, Benjamin F.
Wang, Congrong
Wareham, Nicholas J.
Wennauer, Roman
Wickremasinghe, Ananda R.
Wilsgaard, Tom
Wilson, James F.
Wiltshire, Steven
Winckler, Wendy
Wong, Tien Yin
Wood, Andrew R.
Wu, Jer-Yuarn
Wu, Ying
Yamamoto, Ken
Yamauchi, Toshimasa
Yang, Mingyu
Yengo, Loic
Yokota, Mitsuhiro
Young, Robin D.
Zabaneh, Delilah
Zhang, Fan
Zhang, Rong
Zheng, Wei
Zimmet, Paul Z.
Altshuler, David
Bowden, Donald W.
Cho, Yoon Shin
Cox, Nancy J.
Cruz, Miguel
Hanis, Craig L.
Kooner, Jaspal Singh S.
Lee, Jong-Young
Seielstad, Mark
Teo, Yik Ying
Boehnke, Michael
Parra, Esteban
Chambers, John C.
Tai, E. Shyong
McCarthy, Mark I.
Morris, Andrew P.

PMCID

PMC3969612