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

Anubha Mahajan, Min Jin Go, Weihua Zhang, Jennifer E. Below, Kyle J. Gaulton, Teresa Ferreira, Momoko Horikoshi, Andrew D. Johnson, Maggie C Y Ng, Inga Prokopenko, Danish Saleheen, Xu Wang, Eleftheria Zeggini, Goncalo R. Abecasis, Linda S. Adair, Peter Almgren, Mustafa Atalay, Tin Aung, Damiano Baldassarre, Beverley BalkauYuqian Bao, Anthony H. Barnett, Ines Barroso, Abdul Basit, Latonya F. Been, John Beilby, Graeme I. Bell, Rafn Benediktsson, Richard N. Bergman, Bernhard OBoehm, Eric Boerwinkle, Lori L. Bonnycastle, Noël Burtt, Qiuyin Cai, Harry Campbell, Jason Carey, Stephane Cauchi, Mark Caulfield, Juliana C N Chan, Li Ching Chang, Tien Jyun Chang, Yi Cheng Chang, Guillaume Charpentier, Chien Hsiun Chen, Han Chen, Yuan Tsong Chen, Kee Seng Chia, Manickam Chidambaram, Peter S. Chines, Nam H. Cho, Young Min Cho, Lee Ming Chuang, Francis S. Collins, Marilyn C. Cornelis, David J. Couper, Andrew T. Crenshaw, Rob M. Van Dam, John Danesh, Debashish Das, Ulf De Faire, George Dedoussis, Panos Deloukas, Antigone S. Dimas, Christian Dina, Alex S F Doney, Peter J. Donnelly, Mozhgan Dorkhan, Cornelia Van Duijn, Josée Dupuis, Sarah Edkins, Paul Elliott, Valur Emilsson, Raimund Erbel, Johan G. Eriksson, Jorge Escobedo, Tonu Esko, Elodie Eury, Jose C. Florez, Pierre Fontanillas, Nita G. Forouhi, Tom Forsen, Caroline Fox, Ross M. Fraser, Timothy M. Frayling, Philippe Froguel, Philippe Frossard, Yutang Gao, Karl Gertow, Christian Gieger, Bruna Gigante, Harald Grallert, George B. Grant, Leif C. Groop, Christopher J. Groves, Elin Grundberg, Candace Guiducci, Anders Hamsten, Bok Ghee Han, Kazuo Hara, Neelam Hassanali, Andrew T. Hattersley, Caroline Hayward, Asa K. Hedman, Christian Herder, Albert Hofman, Oddgeir L. Holmen, Kees Hovingh, Astradur B. Hreidarsson, Cheng Hu, Frank B. Hu, Jennie Hui, Steve E. Humphries, Sarah E. Hunt, David J. Hunter, Kristian Hveem, Zafar I. Hydrie, Hiroshi Ikegami, Thomas Illig, Erik Ingelsson, Muhammed Islam, Bo Isomaa, Anne U. Jackson, Tazeen Jafar, Alan James, Weiping Jia, Karl Heinz Jöckel, Anna Jonsson, Jeremy B M Jowett, Takashi Kadowaki, Hyun Min Kang, Stavroula Kanoni, Wen Hong L Kao, Sekar Kathiresan, Norihiro Kato, Prasad Katulanda, Sirkka M. Keinanen-Kiukaanniemi, Ann M. Kelly, Hassan Khan, Kay Tee Khaw, Chiea Chuen Khor, Hyung Lae Kim, Sangsoo Kim, Young Jin Kim, Leena Kinnunen, Norman Klopp, Augustine Kong, Eeva Korpi-Hyövälti, Sudhir Kowlessur, Peter Kraft, Jasmina Kravic, Malene M. Kristensen, S. Krithika, Ashish Kumar, Jesus Kumate, Johanna Kuusisto, Soo Heon Kwak, Markku Laakso, Vasiliki Lagou, Timo A. Lakka, Claudia Langenberg, Cordelia Langford, Robert Lawrence, Karin Leander, Jen Mai Lee, Nanette R. Lee, Man Li, Xinzhong Li, Yun Li, Junbin Liang, Samuel Liju, Wei Yen Lim, Lars Lind, Cecilia M. Lindgren, Eero Lindholm, Ching Ti Liu, Jian Jun Liu, Stéphane Lobbens, Jirong Long, Ruth J F Loos, Wei Lu, Jianan Luan, Valeriya Lyssenko, Ronald C. WMa, Shiro Maeda, Reedik Mägi, Satu Männistö, David R. Matthews, James B. Meigs, Olle Melander, Andres Metspalu, Julia Meyer, Ghazala Mirza, Evelin Mihailov, Susanne Moebus, Viswanathan Mohan, Karen L. Mohlke, Andrew D. Morris, Thomas WMühleisen, Martina Müller-Nurasyid, Bill Musk, Jiro Nakamura, Eitaro Nakashima, Pau Navarro, Peng Keat Ng, Alexandra C. Nica, Peter M. Nilsson, Inger Njølstad, Markus M. Nöthen, Keizo Ohnaka, Twee Hee Ong, Katharine R. Owen, Colin N A Palmer, James S. Pankow, Kyong Soo Park, Melissa Parkin, Sonali Pechlivanis, Nancy L. Pedersen, Leena Peltonen, John R B Perry, Annette Peters, Janani M. Pinidiyapathirage, Carl G P Platou, Simon Potter, Jackie F. Price, Lu Qi, Venkatesan Radha, Loukianos Rallidis, Asif Rasheed, Wolfgang Rathmann, Rainer Rauramaa, Soumya Raychaudhuri, N. William Rayner, Simon D. Rees, Emil Rehnberg, Samuli Ripatti, Neil Robertson, Michael Roden, Elizabeth J. Rossin, Igor Rudan, Denis Rybin, Timo E. Saaristo, Veikko Salomaa, Juha Saltevo, Maria Samuel, Dharambir KSanghera, Jouko Saramies, James Scott, Laura J. Scott, Robert A. Scott, Ayellet V. Segrè, Joban Sehmi, Bengt Sennblad, Nabi Shah, Sonia Shah, A. Samad Shera, Xiao Ou Shu, Alan R. Shuldiner, Gunnar Sigurosson, Eric Sijbrands, Angela Silveira, Xueling Sim, Suthesh Sivapalaratnam, Kerrin S. Small, Wing Yee So, Alena Stančáková, Kari Stefansson, Gerald Steinbach, Valgerdur Steinthorsdottir, Kathleen Stirrups, Rona J. Strawbridge, Heather M. Stringham, Qi Sun, Chen Suo, Ann Christine Syvänen, Ryoichi Takayanagi, Fumihiko Takeuchi, Wan Ting Tay, Tanya M. Teslovich, Barbara Thorand, Gudmar Thorleifsson, Unnur Thorsteinsdottir, Emmi Tikkanen, Joseph Trakalo, Elena Tremoli, Mieke D. Trip, Fuu Jen Tsai, Tiinamaija Tuomi, Jaakko Tuomilehto, Andre G. Uitterlinden, Adan Valladares-Salgado, Sailaja Vedantam, Fabrizio Veglia, Benjamin F. Voight, Congrong Wang, Nicholas J. Wareham, Roman Wennauer, Ananda R. Wickremasinghe, Tom Wilsgaard, James F. Wilson, Steven Wiltshire, Wendy Winckler, Tien Yin Wong, Andrew R. Wood, Jer Yuarn Wu, Ying Wu, Ken Yamamoto, Toshimasa Yamauchi, Mingyu Yang, Loic Yengo, Mitsuhiro Yokota, Robin Young, Delilah Zabaneh, Fan Zhang, Rong Zhang, Wei Zheng, Paul Z. Zimmet, David Altshuler, Donald W. Bowden, Yoon Shin Cho, Nancy J. Cox, Miguel Cruz, Craig L. Hanis, Jaspal Kooner, Jong Young Lee, Mark Seielstad, Yik Ying Teo, Michael Boehnke*, Esteban J. Parra, John C. Chambers, E. Shyong Tai, Mark I. McCarthy, Andrew P. Morris

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

606 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)234-244
Number of pages11
JournalNature Genetics
Volume46
Issue number3
DOIs
StatePublished - Mar 2014

ASJC Scopus subject areas

  • Genetics

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