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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2014-03

AUTHORS

DIAbetes Genetics Replication And Meta-analysis Consortium, Asian Genetic Epidemiology Network Type 2 Diabetes Consortium, South Asian Type 2 Diabetes Consortium, Mexican American Type 2 Diabetes Consortium, Type 2 Diabetes Genetic Exploration by Next-generation sequencing in multi-Ethnic Samples Consortium, 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 Balkau, Yuqian Bao, Anthony H Barnett, Ines Barroso, Abdul Basit, Latonya F Been, John Beilby, Graeme I Bell, Rafn Benediktsson, Richard N Bergman, Bernhard O Boehm, 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, Jian'an Luan, Valeriya Lyssenko, Ronald C W, 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 W Mühleisen, 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 K Sanghera, 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 Sigurðsson, Eric Sijbrands, Angela Silveira, Xueling Sim, Suthesh Sivapalaratnam, Kerrin S Small, 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

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. More... »

PAGES

234-244

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  • Journal

    TITLE

    Nature Genetics

    ISSUE

    3

    VOLUME

    46

    Author Affiliations

  • Wellcome Centre for Human Genetics
  • Korea National Institute of Health
  • Imperial College London
  • University of Washington
  • University of Oxford
  • National Heart Lung and Blood Institute
  • Wake Forest University
  • Center for Non-Communicable Diseases
  • National University of Singapore
  • Wellcome Sanger Institute
  • University of Michigan–Ann Arbor
  • University of North Carolina System
  • Lund University
  • University of Eastern Finland
  • University of Milan
  • University of Paris-Sud
  • University of Birmingham
  • Institute of Metabolic Science
  • Baqai Institute of Diabetology and Endocrinology
  • University of Oklahoma Health Sciences Center
  • University of Western Australia
  • University of Chicago
  • National University Hospital of Iceland
  • University of Southern California
  • Baylor College of Medicine
  • National Human Genome Research Institute
  • Broad Institute
  • Western General Hospital
  • Délégation Nord, Pas-de-Calais et Picardie
  • Queen Mary University of London
  • Institute of Biomedical Sciences, Academia Sinica
  • National Taiwan University Hospital
  • China Medical University
  • Boston University
  • Ajou University
  • Seoul National University
  • National Taiwan University
  • Harvard University
  • University of North Carolina at Chapel Hill
  • University of Cambridge
  • Ealing Hospital NHS Trust
  • Karolinska Institute
  • Harokopio University
  • Alexander Fleming Biomedical Sciences Research Center
  • University of Nantes
  • Erasmus University Medical Center
  • Icelandic Heart Association
  • Folkhälsans Forskningscentrum
  • Mexican Social Security Institute
  • Boston Children's Hospital
  • Massachusetts General Hospital
  • University of Helsinki
  • University of Edinburgh
  • University of Exeter
  • Shanghai Cancer Institute
  • Karolinska University Hospital
  • Helmholtz Zentrum München
  • German Center for Diabetes Research
  • King's College London
  • University of Tokyo
  • German Diabetes Center - Leibniz Institute for Diabetes Research at Heinrich Heine University Düsseldorf
  • Norwegian University of Science and Technology
  • University College London
  • Kindai University
  • Hannover Medical School
  • Uppsala University Hospital
  • Aga Khan University
  • Essen University Hospital
  • Johns Hopkins University
  • National Center For Global Health and Medicine
  • University of Colombo
  • Oulu University Hospital
  • Genome Institute of Singapore
  • Ewha Womans University
  • Soongsil University
  • National Institute for Health and Welfare
  • deCODE Genetics (Iceland)
  • Seinäjoen Keskussairaala
  • University of Toronto
  • Kuopion Liikuntalääketieteen Tutkimuslaitos
  • University of San Carlos
  • Beijing Genomics Institute
  • Icahn School of Medicine at Mount Sinai
  • Shanghai Institute of Hypertension
  • University of Tartu
  • Dr. Mohan's Diabetes Specialities Centre
  • University of Bonn
  • Ludwig Maximilian University of Munich
  • Sir Charles Gairdner Hospital
  • Nagoya University
  • Chubu Rosai Hospital
  • University of Geneva
  • The Arctic University of Norway
  • Kyushu University
  • Churchill Hospital
  • University of Minnesota
  • Institute for Molecular Medicine Finland
  • University of Kelaniya
  • Levanger Hospital
  • University General Hospital Attikon
  • Kuopio University Hospital
  • Heinrich Heine University Düsseldorf
  • Pirkanmaa Hospital District
  • Central Finland Health Care District
  • South Karelia Central Hospital
  • University of Maryland, Baltimore
  • University of Ulm
  • Uppsala University
  • Singapore National Eye Center
  • King Abdulaziz University
  • Centro Medico Nacional Siglo XXI
  • Centro Cardiologico Monzino
  • University of Pennsylvania
  • Centre for Eye Research Australia
  • Inria research centre Lille - Nord Europe
  • Aichi Gakuin University
  • Hallym University
  • The University of Texas Health Science Center at Houston
  • Imperial College Healthcare NHS Trust
  • Blood Systems Research Institute
  • Duke NUS Graduate Medical School
  • University of Liverpool
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ng.2897

    DOI

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

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1013812051

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/24509480


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