Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility
Journal
Nature genetics
Journal Volume
46
Journal Issue
3
Pages
234
Date Issued
2014-03
Author(s)
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, 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 C N
Chang, Li-Ching
Charpentier, Guillaume
Chen, Chien-Hsiun
Chen, Han
Chen, Yuan-Tsong
Chia, Kee-Seng
Chidambaram, Manickam
Chines, Peter S
Cho, Nam H
Cho, Young Min
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 B M
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 J F
Lu, Wei
Luan, Jian'an
Lyssenko, Valeriya
Ma, Ronald C W
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 N A
Pankow, James S
Park, Kyong Soo
Parkin, Melissa
Pechlivanis, Sonali
Pedersen, Nancy L
Peltonen, Leena
Perry, John R B
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
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.
Subjects
ASSOCIATION ANALYSES; GLUCOSE-HOMEOSTASIS; LOCI; VARIANTS; INDIVIDUALS; CHROMATIN; IDENTIFY
SDGs
Publisher
NATURE PUBLISHING GROUP
Type
journal article