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

  • Author(s): 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
  • Mahajan, Anubha
  • Go, Min Jin
  • Zhang, Weihua
  • Below, Jennifer E
  • Gaulton, Kyle J
  • Ferreira, Teresa
  • Horikoshi, Momoko
  • Johnson, Andrew D
  • Ng, Maggie CY
  • Prokopenko, Inga
  • Saleheen, Danish
  • Wang, Xu
  • Zeggini, Eleftheria
  • Abecasis, Goncalo 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
  • Bonnycastle, Lori L
  • Burtt, Noël
  • Cai, Qiuyin
  • Campbell, Harry
  • Carey, Jason
  • Cauchi, Stephane
  • Caulfield, Mark
  • Chan, Juliana CN
  • 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
  • Chuang, Lee-Ming
  • Collins, Francis S
  • Cornelis, Marylin 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
  • Donnelly, Peter J
  • Dorkhan, Mozhgan
  • van Duijn, Cornelia
  • Dupuis, Josée
  • 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
  • Fraser, Ross M
  • Frayling, Timothy M
  • Froguel, Philippe
  • Frossard, Philippe
  • Gao, Yutang
  • Gertow, Karl
  • Gieger, Christian
  • Gigante, Bruna
  • Grallert, Harald
  • Grant, George B
  • Grrop, Leif C
  • Groves, Chrisropher 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, 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
  • Jia, Weiping
  • Jöckel, Karl-Heinz
  • Jonsson, Anna
  • Jowett, Jeremy BM
  • Kadowaki, Takashi
  • Kang, Hyun Min
  • Kanoni, Stavroula
  • Kao, Wen Hong L
  • Kathiresan, Sekar
  • Kato, Norihiro
  • Katulanda, Prasad
  • Keinanen-Kiukaanniemi, Kirkka 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-Hyövälti, 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
  • Leander, Karin
  • Lee, Jen-Mai
  • 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, Jian Jun
  • Lobbens, Stéphane
  • Long, Jirong
  • Loos, Ruth JF
  • Lu, Wei
  • Luan, Jian'an
  • Lyssenko, Valeriya
  • Ma, Ronald CW
  • Maeda, Shiro
  • Mägi, Reedik
  • Männisto, 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
  • Mühleisen, Thomas W
  • Müller-Nurasyid, Martina
  • Musk, Bill
  • Nakamura, Jiro
  • Nakashima, Eitaro
  • Navarro, Pau
  • Ng, Peng-Keat
  • Nica, Alexandra C
  • Nilsson, Peter M
  • Njølstad, Inger
  • Nöthen, Markus M
  • Ohnaka, Keizo
  • Ong, Twee Hee
  • Owen, Katharine R
  • Palmer, Colin NA
  • Pankow, James S
  • Park, Kyong Soo
  • Parkin, Melissa
  • Pechlivanis, Sonali
  • Pedersen, Nancy L
  • Peltonen, Leena
  • Perry, John RB
  • Peters, Annette
  • Pinidiyapathirage, Janini M
  • Platou, Carl G
  • Potter, Simon
  • Price, Jackie F
  • Qi, Lu
  • Radha, Venkatesan
  • Rallidis, Loukianos
  • Rasheed, Asif
  • Rathman, Wolfgang
  • Rauramaa, Rainer
  • Raychaudhuri, Soumya
  • Rayner, N William
  • Rees, Simon D
  • Rehnberg, Emil
  • Ripatti, Samuli
  • Robertson, Neil
  • 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
  • Segrè, Ayellet V
  • Sehmi, Joban
  • Sennblad, Bengt
  • Shah, Nabi
  • Shah, Sonia
  • Shera, A Samad
  • Shu, Xiao Ou
  • Shuldiner, Alan R
  • Sigurđsson, Gunnar
  • Sijbrands, Eric
  • Silveira, Angela
  • Sim, Xueling
  • Sivapalaratnam, Suthesh
  • Small, Kerrin S
  • So, Wing Yee
  • Stančáková, Alena
  • Stefansson, Kari
  • Steinbach, Gerald
  • Steinthorsdottir, Valgerdur
  • Stirrups, Kathleen
  • Strawbridge, Rona J
  • Stringham, Heather M
  • Sun, Qi
  • Suo, Chen
  • Syvänen, 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
  • 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
  • Lee, Jong-Young
  • Seielstad, Mark
  • Teo, Yik Ying
  • Boehnke, Michael
  • Parra, Esteban J
  • Chambers, Jonh C
  • Tai, E Shyong
  • McCarthy, Mark I
  • Morris, Andrew P
  • et al.

Published Web Location

https://doi.org/10.1038/ng.2897
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.

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