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 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; Noel 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; Josee 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; South Asian Type Diabet SAT2D Cons

doi:10.1038/ng.2897

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

Journal article

Peer reviewed

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, …

Nature genetics, Vol.46(3), pp.234-244

01/03/2014

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

PMID: 24509480

Abstract

Genetics & Heredity

Life Sciences & Biomedicine

Science & Technology

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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Title: Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility
Creators: Anubha Mahajan - University of Oxford
Min Jin Go - Korea National Institute of Health
Weihua Zhang - Imperial College London
Jennifer E. Below - University of Washington
Kyle J. Gaulton - Wellcome Centre for Human Genetics
Teresa Ferreira - Wellcome Centre for Human Genetics
Momoko Horikoshi - Wellcome Centre for Human Genetics
Andrew D. Johnson - Framingham Heart Study
Maggie C. Y. Ng - Wake Forest University
Inga Prokopenko - Wellcome Centre for Human Genetics
Danish Saleheen - University of Cambridge
Xu Wang - National University of Singapore
Eleftheria Zeggini - Wellcome Sanger Institute
Goncalo R. Abecasis - University of Michigan–Ann Arbor
Linda S. Adair - University of North Carolina at Chapel Hill
Peter Almgren - Scania
Mustafa Atalay - University of Eastern Finland
Tin Aung - Singapore National Eye Center
Damiano Baldassarre - Centro Cardiologico Monzino
Beverley Balkau - Centre de recherche en Epidémiologie et Santé des Populations
Yuqian Bao - Shanghai Sixth People's Hospital
Anthony H. Barnett - University of Birmingham
Ines Barroso - Wellcome Sanger Institute
Abdul Basit - Baqai Institute of Diabetology and Endocrinology
Latonya F. Been - University of Oklahoma Health Sciences Center
John Beilby - Sir Charles Gairdner Hospital
Graeme I. Bell - University of Chicago
Rafn Benediktsson - University of Iceland
Richard N. Bergman - Cedars-Sinai Medical Center
Bernhard O. Boehm - College Station Medical Center
Eric Boerwinkle - The University of Texas Health Science Center at Houston
Lori L. Bonnycastle - National Human Genome Research Institute
Noel Burtt - Broad Institute
Qiuyin Cai - Vanderbilt University
Harry Campbell - University of Edinburgh
Jason Carey - Broad Institute
Stephane Cauchi - Centre National de la Recherche Scientifique
Mark Caulfield - William Harvey Research Institute
Juliana C. N. Chan - Chinese University of Hong Kong
Li-Ching Chang - Institute of Biomedical Sciences, Academia Sinica
Tien-Jyun Chang - College Station Medical Center
Yi-Cheng Chang - College Station Medical Center
Guillaume Charpentier - Centre Hospitalier Sud Francilien
Chien-Hsiun Chen - Institute of Biomedical Sciences, Academia Sinica
Han Chen - National Taiwan University Hospital
Yuan-Tsong Chen - Institute of Biomedical Sciences, Academia Sinica
Kee-Seng Chia - Natl Univ Singapore, Dept Epidemiol & Publ Hlth, Singapore 117548, Singapore
Manickam Chidambaram - Madras Diabetes Research Foundation
Peter S. Chines - National Human Genome Research Institute
Nam H. Cho - Ajou University
Young Min Cho - Seoul National University
Lee-Ming Chuang - College Station Medical Center
Francis S. Collins - National Human Genome Research Institute
Marilyn C. Cornelis - Harvard University
David J. Couper - University of North Carolina at Chapel Hill
Andrew T. Crenshaw - Broad Institute
Rob M. van Dam - Harvard University
John Danesh - University of Cambridge
Debashish Das - Ealing Hospital
Ulf de Faire - Karolinska Institutet
George Dedoussis - Harokopio University of Athens
Panos Deloukas - Wellcome Sanger Institute
Antigone S. Dimas - Wellcome Centre for Human Genetics
Christian Dina - Inserm
Alex S. F. Doney - Ninewells Hospital
Peter J. Donnelly - University of Oxford
Mozhgan Dorkhan - Lund University
Cornelia van Duijn - Erasmus MC
Josee Dupuis - Framingham Heart Study
Sarah Edkins - Wellcome Sanger Institute
Paul Elliott - Imperial College London
Valur Emilsson - Icelandic Heart Association
Raimund Erbel - West German Heart and Vascular Center Essen
Johan G. Eriksson - Finnish Institute for Health and Welfare
Jorge Escobedo - Mexican Social Security Institute
Tonu Esko - University of Tartu
Elodie Eury - Institut Pasteur de Lille
Jose C. Florez - Broad Institute
Pierre Fontanillas - Broad Institute
Nita G. Forouhi - MRC Epidemiology Unit
Tom Forsen - University of Helsinki
Caroline Fox - Framingham Heart Study
Ross M. Fraser - University of Edinburgh
Timothy M. Frayling - University of Exeter
Philippe Froguel - Imperial College London
Philippe Frossard - Center for Non-Communicable Diseases
Yutang Gao - Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China
Karl Gertow - Karolinska Institutet
Christian Gieger - Helmholtz Zentrum München
Bruna Gigante - Karolinska Institutet
Harald Grallert - Helmholtz Zentrum München
George B. Grant - Broad Institute
Leif C. Groop - Scania
Christopher J. Groves - Oxford Centre for Diabetes, Endocrinology and Metabolism
Elin Grundberg - King's College London
Candace Guiducci - Massachusetts Institute of Technology
Anders Hamsten - Karolinska Institutet
Bok-Ghee Han - Natl Inst Hlth, Ctr Genome Sci, Gangoe Myeon, Yeonje Ri, South Korea
Kazuo Hara - The University of Tokyo
Neelam Hassanali - Oxford Centre for Diabetes, Endocrinology and Metabolism
South Asian Type Diabet SAT2D Cons
Publication Details: Nature genetics, Vol.46(3), pp.234-244
Publisher: NATURE PORTFOLIO
Number of pages: 13
Date published: 01/03/2014
Grant note: SSA/IMMS/ISSSTE-CONACYT 2012-2; clave 150352; IMSS R-2011-785-018; CONACYT Salud-2007-C01-71068 / Mexico Convocatoria G0601261 / Medical Research Council UK; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) CZB/4/672; CZB/4/710 / Chief Scientist Office; Chief Scientist Office - Scotland HEALTH-F4-2007-201413 / European Commission (ENGAGE FP7) MC_UU_12015/5; G0801056; G1002084; MC_PC_U127592696; MR/K006584/1; MR/L003120/1; MC_UU_12015/1; G0601261; G9521010; MC_UU_12015/2; MC_U106179471; MC_UP_A100_1003 / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) MC_PC_U127592696; MC_UP_A100_1003; MR/L003120/1; G9521010; MC_UU_12015/2; G0801056; G1002084; MC_UU_12015/5; G0601261; MC_UU_12015/1 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) RG/08/008/25291; RG/08/014/24067 / British Heart Foundation NF-SI-0611-10219; NF-SI-0611-10099; NF-SI-0611-10136; NF-SI-0512-10165; NF-SI-0512-10113 / National Institute for Health Research; National Institutes of Health Research (NIHR) WT098017; WT090532; WT090367; WT098381; WT081682; WT085475 / Wellcome Trust DK062370; HG000376; DK085584; DK085545; DK073541; DK085501 / US National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
Identifiers: 99928708502346
Academic Unit: School of Biosciences
Language: English
Resource Type: Journal article

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

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