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

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

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Authors

  • 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
  • Ghazala Mirza
  • Thomas W. Mühleisen
  • Bill Musk
  • Melissa Parkin
  • Loukianos Rallidis
  • Jouko Saramies
  • Bengt Sennblad
  • Sonia Shah
  • Gunnar Sigurdsson
  • Angela Silveira
  • Gerald Steinbach
  • Barbara Thorand
  • Joseph Trakalo
  • Fabrizio Veglia
  • Roman Wennauer
  • Wendy Winckler
  • Delilah Zabaneh
  • Harry Campbell
  • Cornelia van Duijn
  • Andre G. Uitterlinden
  • Albert Hofman
  • Eric Sijbrands
  • Goncalo R. Abecasis
  • Katharine R. Owen
  • Eleftheria Zeggini
  • Mieke D. Trip
  • Nita G. Forouhi
  • Ann-Christine Syvanen
  • Johan G. Eriksson
  • Leena Peltonen
  • Markus M. Noethen
  • Beverley Balkau
  • Colin N. A. Palmer
  • Valeriya Lyssenko
  • Tiinamaija Tuomi
  • Bo Isomaa
  • David J. Hunter
  • Lu Qi
  • Alan R. Shuldiner
  • Michael Roden
  • Ines Barroso
  • Tom Wilsgaard
  • John Beilby
  • Kees Hovingh
  • Jackie F. Price
  • James F. Wilson
  • Rainer Rauramaa
  • Timo A. Lakka
  • Lars Lind
  • George Dedoussis
  • Inger Njolstad
  • Nancy L. Pedersen
  • Kay-Tee Khaw
  • Nicholas J. Wareham
  • Sirkka M. Keinanen-Kiukaanniemi
  • Timo E. Saaristo
  • Eeva Korpi-Hyovalti
  • Juha Saltevo
  • Markku Laakso
  • Johanna Kuusisto
  • Andres Metspalu
  • Francis S. Collins
  • Karen L. Mohlke
  • Richard N. Bergman
  • Jaakko Tuomilehto
  • Bernhard O. Boehm
  • Christian Gieger
  • Kristian Hveem
  • Stephane Cauchi
  • Philippe Froguel
  • Damiano Baldassarre
  • Elena Tremoli
  • Steve E. Humphries
  • Danish Saleheen
  • John Danesh
  • Erik Ingelsson
  • Samuli Ripatti
  • Veikko Salomaa
  • Raimund Erbel
  • Karl-Heinz Jöckel
  • Susanne Moebus
  • Annette Peters
  • Thomas Illig
  • Ulf de Faire
  • Anders Hamsten
  • Peter J. Donnelly
  • Timothy M. Frayling
  • Andrew T. Hattersley
  • Eric Boerwinkle
  • Olle Melander
  • Sekar Kathiresan
  • Peter M. Nilsson
  • Panos Deloukas
  • Unnur Thorsteinsdottir
  • Leif C. Groop
  • Kari Stefansson
  • Frank Hu
  • James S. Pankow
  • Josee Dupuis
  • James B. Meigs
  • David Altshuler
  • Michael Boehnke
  • Mark I. McCarthy
  • DIAbet Genetics Replication, Asian Genetic Epidemiology, Genetic Invest ANthropometric, Meta-Anal Glucose Insulin-Related, S Asian Type 2 Diabet SAT2D, Wellcome Trust Case Control

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Info

Original languageEnglish
Pages981-990
Number of pages12
JournalNature Genetics
Journal publication dateSep 2012
Journal number9
Volume44
DOIs
StatePublished

Abstract

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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