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Leif Groop

Leif Groop

Principal investigator

Leif Groop

Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge

Author

  • Richa Saxena
  • Marie-France Hivert
  • Claudia Langenberg
  • Toshiko Tanaka
  • James S. Pankow
  • Peter Vollenweider
  • Valeriya Lyssenko
  • Nabila Bouatia-Naji
  • Josee Dupuis
  • Anne U. Jackson
  • W. H. Linda Kao
  • Man Li
  • Nicole L. Glazer
  • Alisa K. Manning
  • Jian'an Luan
  • Heather M. Stringham
  • Inga Prokopenko
  • Toby Johnson
  • Niels Grarup
  • Trine W. Boesgaard
  • Cecile Lecoeur
  • Peter Shrader
  • Jeffrey O'Connell
  • Erik Ingelsson
  • David J. Couper
  • Kenneth Rice
  • Kijoung Song
  • Camilla H. Andreasen
  • Christian Dina
  • Anna Koettgen
  • Olivier Le Bacquer
  • Francois Pattou
  • Jalal Taneera
  • Valgerdur Steinthorsdottir
  • Denis Rybin
  • Kristin Ardlie
  • Michael Sampson
  • Lu Qi
  • Mandy van Hoek
  • Michael N. Weedon
  • Yurii S. Aulchenko
  • Benjamin F. Voight
  • Harald Grallert
  • Beverley Balkau
  • Richard N. Bergman
  • Suzette J. Bielinski
  • Amelie Bonnefond
  • Lori L. Bonnycastle
  • Knut Borch-Johnsen
  • Yvonne Boettcher
  • Eric Brunner
  • Thomas A. Buchanan
  • Suzannah J. Bumpstead
  • Christine Cavalcanti-Proenca
  • Guillaume Charpentier
  • Yii-Der Ida Chen
  • Peter S. Chines
  • Francis S. Collins
  • Marilyn Cornelis
  • Gabriel J. Crawford
  • Jerome Delplanque
  • Alex Doney
  • Josephine M. Egan
  • Michael R. Erdos
  • Mathieu Firmann
  • Nita G. Forouhi
  • Caroline S. Fox
  • Mark O. Goodarzi
  • Juergen Graessler
  • Aroon Hingorani
  • Bo Isomaa
  • Torben Jorgensen
  • Mika Kivimaki
  • Peter Kovacs
  • Knut Krohn
  • Meena Kumari
  • Torsten Lauritzen
  • Claire Levy-Marchal
  • Vladimir Mayor
  • Jarred B. McAteer
  • David Meyre
  • Braxton D. Mitchell
  • Karen L. Mohlke
  • Mario A. Morken
  • Narisu Narisu
  • Colin N. A. Palmer
  • Ruth Pakyz
  • Laura Pascoe
  • Felicity Payne
  • Daniel Pearson
  • Wolfgang Rathmann
  • Annelli Sandbaek
  • Avan Aihie Sayer
  • Laura J. Scott
  • Stephen J. Sharp
  • Eric Sijbrands
  • Andrew Singleton
  • David S. Siscovick
  • Nicholas L. Smith
  • Thomas Sparso
  • Amy J. Swift
  • Holly Syddall
  • Gudmar Thorleifsson
  • Anke Toenjes
  • Tiinamaija Tuomi
  • Jaakko Tuomilehto
  • Timo T. Valle
  • Gerard Waeber
  • Andrew Walley
  • Dawn M. Waterworth
  • Eleftheria Zeggini
  • Jing Hua Zhao
  • Thomas Illig
  • H. Erich Wichmann
  • James F. Wilson
  • Cornelia van Duijn
  • Frank B. Hu
  • Andrew D. Morris
  • Timothy M. Frayling
  • Andrew T. Hattersley
  • Unnur Thorsteinsdottir
  • Kari Stefansson
  • Peter Nilsson
  • Ann-Christine Syvanen
  • Alan R. Shuldiner
  • Mark Walker
  • Stefan R. Bornstein
  • Peter Schwarz
  • Gordon H. Williams
  • David M. Nathan
  • Johanna Kuusisto
  • Markku Laakso
  • Cyrus Cooper
  • Michael Marmot
  • Luigi Ferrucci
  • Vincent Mooser
  • Michael Stumvoll
  • Ruth J. F. Loos
  • David Altshuler
  • Bruce M. Psaty
  • Jerome I. Rotter
  • Eric Boerwinkle
  • Torben Hansen
  • Oluf Pedersen
  • Jose C. Florez
  • Mark I. McCarthy
  • Michael Boehnke
  • Ines Barroso
  • Robert Sladek
  • Philippe Froguel
  • James B. Meigs
  • Leif Groop
  • Nicholas J. Wareham
  • Richard M. Watanabe

Summary, in English

Glucose levels 2 h after an oral glucose challenge are a clinical measure of glucose tolerance used in the diagnosis of type 2 diabetes. We report a meta-analysis of nine genome-wide association studies (n = 15,234 nondiabetic individuals) and a follow-up of 29 independent loci (n = 6,958-30,620). We identify variants at the GIPR locus associated with 2- h glucose level (rs10423928, beta (s.e.m.) = 0.09 (0.01) mmol/l per A allele, P = 2.0 x 10(-15)). The GIPR A-allele carriers also showed decreased insulin secretion (n = 22,492; insulinogenic index, P = 1.0 x 10(-17); ratio of insulin to glucose area under the curve, P = 1.3 x 10(-16)) and diminished incretin effect (n = 804; P = 4.3 x 10(-4)). We also identified variants at ADCY5 (rs2877716, P = 4.2 x 10(-16)), VPS13C (rs17271305, P = 4.1 x 10(-8)), GCKR (rs1260326, P = 7.1 x 10(-11)) and TCF7L2 (rs7903146, P = 4.2 x 10(-10)) associated with 2-h glucose. Of the three newly implicated loci (GIPR, ADCY5 and VPS13C), only ADCY5 was found to be associated with type 2 diabetes in collaborating studies (n = 35,869 cases, 89,798 controls, OR = 1.12, 95% CI 1.09-1.15, P = 4.8 x 10(-18)).

Department/s

  • Genomics, Diabetes and Endocrinology
  • Internal Medicine - Epidemiology
  • EXODIAB: Excellence of Diabetes Research in Sweden
  • EpiHealth: Epidemiology for Health

Publishing year

2010

Language

English

Pages

75-142

Publication/Series

Nature Genetics

Volume

42

Issue

2

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Endocrinology and Diabetes
  • Other Clinical Medicine

Status

Published

Research group

  • Genomics, Diabetes and Endocrinology
  • Internal Medicine - Epidemiology

ISBN/ISSN/Other

  • ISSN: 1546-1718