Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes

Andrew P. Morris; Benjamin F. Voight; Tanya M. Teslovich; Teresa Ferreira; Ayellet V. Segre; Valgerdur Steinthorsdottir; Rona J. Strawbridge; Hassan Khan; Harald Grallert; Anubha Mahajan; Inga Prokopenko; Hyun Min Kang; Christian Dina; Tonu Esko; Ross M. Fraser; Stavroula Kanoni; Ashish Kumar; Vasiliki Lagou; Claudia Langenberg; Jian'an Luan; Cecilia M. Lindgren; Martina Mueller-Nurasyid; Sonali Pechlivanis; N. William Rayner; Laura J. Scott; Steven Wiltshire; Loic Yengo; Leena Kinnunen; Elizabeth J. Rossin; Soumya Raychaudhuri; Andrew D. Johnson; Antigone S. Dimas; Ruth J. F. Loos; Sailaja Vedantam; Han Chen; Jose C. Florez; Caroline Fox; Ching-Ti Liu; Denis Rybin; David J. Couper; Wen Hong L. Kao; Man Li; Marilyn C. Cornelis; Peter Kraft; Qi Sun; Rob M. van Dam; Heather M. Stringham; Peter S. Chines; Krista Fischer; Pierre Fontanillas; Oddgeir L. Holmen; Sarah E. Hunt; Anne U. Jackson; Augustine Kong; Robert Lawrence; Julia Meyer; John R. B. Perry; Carl G. P. Platou; Simon Potter; Emil Rehnberg; Neil Robertson; Suthesh Sivapalaratnam; Alena Stancakova; Kathleen Stirrups; Gudmar Thorleifsson; Emmi Tikkanen; Andrew R. Wood; Peter Almgren; Mustafa Atalay; Rafn Benediktsson; Lori L. Bonnycastle; Noel Burtt; Jason Carey; Guillaume Charpentier; Andrew T. Crenshaw; Alex S. F. Doney; Mozhgan Dorkhan; Sarah Edkins; Valur Emilsson; Elodie Eury; Tom Forsen; Karl Gertow; Bruna Gigante; George B. Grant; Christopher J. Groves; Candace Guiducci; Christian Herder; Astradur B. Hreidarsson; Jennie Hui; Alan James; Anna Jonsson; Wolfgang Rathmann; Norman Klopp; Jasmina Kravic; Kaarel Krjutskov; Cordelia Langford; Karin Leander; Eero Lindholm; Stephane Lobbens; Satu Mannisto; Meta-Anal Glucose Insulin-Related

doi:10.1038/ng.2383

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Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes

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Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes

Andrew P. Morris, Benjamin F. Voight, Tanya M. Teslovich, Teresa Ferreira, Ayellet V. Segre, Valgerdur Steinthorsdottir, Rona J. Strawbridge, Hassan Khan, Harald Grallert, Anubha Mahajan, …

Nature genetics, Vol.44(9), pp.981-990

01/09/2012

DOI: https://doi.org/10.1038/ng.2383

PMID: 22885922

Abstract

Genetics & Heredity

Life Sciences & Biomedicine

Science & Technology

To extend understanding of the genetic architecture and molecular basis of type 2 diabetes (T2D), we conducted a meta-analysis of genetic variants on the Metabochip, including 34,840 cases and 114,981 controls, overwhelmingly of European descent. We identified ten previously unreported T2D susceptibility loci, including two showing sex-differentiated association. Genomewide analyses of these data are consistent with a long tail of additional common variant loci explaining much of the variation in susceptibility to T2D. Exploration of the enlarged set of susceptibility loci implicates several processes, including CREBBP-related transcription, adipocytokine signaling and cell cycle regulation, in diabetes pathogenesis.

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Title: Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes
Creators: Andrew P. Morris - Wellcome Centre for Human Genetics
Benjamin F. Voight - Massachusetts Institute of Technology
Tanya M. Teslovich - University of Michigan–Ann Arbor
Teresa Ferreira - Wellcome Centre for Human Genetics
Ayellet V. Segre - Massachusetts Institute of Technology
Valgerdur Steinthorsdottir - deCODE Genet, Reykjavik, Iceland
Rona J. Strawbridge - Karolinska Institutet
Hassan Khan - University of Cambridge
Harald Grallert - Helmholtz Zentrum München
Anubha Mahajan - Wellcome Centre for Human Genetics
Inga Prokopenko - Wellcome Centre for Human Genetics
Hyun Min Kang - University of Michigan–Ann Arbor
Christian Dina - Inserm
Tonu Esko - University of Tartu
Ross M. Fraser - University of Edinburgh
Stavroula Kanoni - Wellcome Sanger Institute
Ashish Kumar - University of Oxford
Vasiliki Lagou - Wellcome Centre for Human Genetics
Claudia Langenberg - Addenbrooke's Hospital
Jian'an Luan - College Station Medical Center
Cecilia M. Lindgren - University of Oxford
Martina Mueller-Nurasyid - Ludwig-Maximilians-Universität München
Sonali Pechlivanis - University of Duisburg-Essen
N. William Rayner - Wellcome Centre for Human Genetics
Laura J. Scott - University of Michigan–Ann Arbor
Steven Wiltshire - Wellcome Centre for Human Genetics
Loic Yengo - Institut Pasteur de Lille
Leena Kinnunen - Finnish Institute for Health and Welfare
Elizabeth J. Rossin - Broad Institute
Soumya Raychaudhuri - Broad Institute
Andrew D. Johnson - Framingham Heart Study
Antigone S. Dimas - Wellcome Centre for Human Genetics
Ruth J. F. Loos - MRC Epidemiology Unit
Sailaja Vedantam - Broad Institute
Han Chen - Boston University
Jose C. Florez - Center for Human Genetics
Caroline Fox - Framingham Heart Study
Ching-Ti Liu - Boston University
Denis Rybin - Boston University
David J. Couper - University of North Carolina at Chapel Hill
Wen Hong L. Kao - Johns Hopkins University
Man Li - Johns Hopkins University
Marilyn C. Cornelis - Harvard University
Peter Kraft - Harvard University
Qi Sun - Harvard University
Rob M. van Dam - Harvard University
Heather M. Stringham - University of Michigan–Ann Arbor
Peter S. Chines - National Human Genome Research Institute
Krista Fischer - University of Tartu
Pierre Fontanillas - Broad Institute
Oddgeir L. Holmen - Norwegian University of Science and Technology
Sarah E. Hunt - Wellcome Sanger Institute
Anne U. Jackson - University of Michigan–Ann Arbor
Augustine Kong - deCODE Genetics
Robert Lawrence - University of Western Australia
Julia Meyer - Helmholtz Zentrum München
John R. B. Perry - Wellcome Centre for Human Genetics
Carl G. P. Platou - Norwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, Nord Trondelag Hlth Study HUNT Res Ctr, Levanger, Norway
Simon Potter - Wellcome Sanger Institute
Emil Rehnberg - Karolinska Institutet
Neil Robertson - University of Oxford
Suthesh Sivapalaratnam - University of Amsterdam
Alena Stancakova - Kuopio University Hospital
Kathleen Stirrups - Wellcome Sanger Institute
Gudmar Thorleifsson - deCODE Genet, Reykjavik, Iceland
Emmi Tikkanen - Institute for Molecular Medicine Finland
Andrew R. Wood - University of Exeter
Peter Almgren - Scania
Mustafa Atalay - University of Eastern Finland
Rafn Benediktsson - University of Iceland
Lori L. Bonnycastle - National Human Genome Research Institute
Noel Burtt - Broad Institute
Jason Carey - Broad Institute
Guillaume Charpentier - Centre Hospitalier Sud Francilien
Andrew T. Crenshaw - Broad Institute
Alex S. F. Doney - Ninewells Hospital
Mozhgan Dorkhan - Lund University
Sarah Edkins - Wellcome Sanger Institute
Valur Emilsson - Icelandic Heart Association
Elodie Eury - Institut Pasteur de Lille
Tom Forsen - University of Helsinki
Karl Gertow - Karolinska University Hospital
Bruna Gigante - Karolinska Institutet
George B. Grant - Broad Institute
Christopher J. Groves - Oxford Centre for Diabetes, Endocrinology and Metabolism
Candace Guiducci - Massachusetts Institute of Technology
Christian Herder - Deutsches Diabetes-Zentrum e.V.
Astradur B. Hreidarsson - Landspitali Univ Hosp, Dept Endocrinol & Metab, Reykjavik, Iceland
Jennie Hui - Sir Charles Gairdner Hospital
Alan James - College Station Medical Center
Anna Jonsson - Scania
Wolfgang Rathmann - Deutsches Diabetes-Zentrum e.V.
Norman Klopp - Helmholtz Zentrum München
Jasmina Kravic - Scania
Kaarel Krjutskov - University of Tartu
Cordelia Langford - Wellcome Sanger Institute
Karin Leander - Karolinska Institutet
Eero Lindholm - Scania
Stephane Lobbens - Institut Pasteur de Lille
Satu Mannisto - Finnish Institute for Health and Welfare
Meta-Anal Glucose Insulin-Related
Publication Details: Nature genetics, Vol.44(9), pp.981-990
Publisher: Springer Nature
Number of pages: 12
Date published: 01/09/2012
Grant note: GR072960; 076113; 077016; 081682; 083948; 083270; 084711; 086596; 090367; 090532; 098051 / Wellcome Trust Narpes Health Care Foundation (Finland) Nord-Trondelag County Council (Norway) Munich Center of Health Sciences (MC Health) (Germany) Groupe d'Etude des Maladies Metaboliques et Systemiques (France) Swedish Research Council Karolinska Institutet (Sweden); Karolinska Institutet 4/26/2010 / Social Insurance Institution of Finland Association Francaise des Diabetiques Federal Ministry of Education and Research (BMBF) (Germany); Federal Ministry of Education & Research (BMBF)
Identifiers: 99928923302346
Academic Unit: School of Biosciences
Language: English
Resource Type: Journal article

Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes

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