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

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; GIANT Consortium

doi:10.1038/ng.521

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

Journal article

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

Richa Saxena, Marie-France Hivert, Claudia Langenberg, Toshiko Tanaka, James S. Pankow, Peter Vollenweider, Valeriya Lyssenko, Nabila Bouatia-Naji, Josee Dupuis, Anne U. Jackson, …

Nature genetics, Vol.42(2), pp.142-U75

01/02/2010

DOI: https://doi.org/10.1038/ng.521

PMCID: PMC2922003

PMID: 20081857

Abstract

Genetics & Heredity

Life Sciences & Biomedicine

Science & Technology

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)).

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Title: Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge
Creators - without role: Richa Saxena - Massachusetts Institute of Technology
Marie-France Hivert - College Station Medical Center
Claudia Langenberg - Massachusetts Rehabilitation Commission
Toshiko Tanaka - Medstar Res Inst, Baltimore, MD USA
James S. Pankow - University of Minnesota
Peter Vollenweider - College Station Medical Center
Valeriya Lyssenko - Malmö University
Nabila Bouatia-Naji - Univ Lille 2, Inst Pasteur, CNRS, Unite Mixte Rech 8090, Lille, France
Josee Dupuis - Boston University
Anne U. Jackson - Biostat
W. H. Linda Kao - Johns Hopkins University
Man Li - Johns Hopkins University
Nicole L. Glazer - University of Washington
Alisa K. Manning - Boston University
Jian'an Luan - Massachusetts Rehabilitation Commission
Heather M. Stringham - Biostat
Inga Prokopenko - University of Oxford
Toby Johnson - University of Lausanne
Niels Grarup - Hagedorn Res Inst, Gentofte, Denmark
Trine W. Boesgaard - Hagedorn Res Inst, Gentofte, Denmark
Cecile Lecoeur - University of Lille
Peter Shrader - College Station Medical Center
Jeffrey O'Connell - Supreme Council Of Health
Erik Ingelsson - Karolinska Institutet
David J. Couper - Biostat
Kenneth Rice - University of Washington
Kijoung Song - GlaxoSmithKline
Camilla H. Andreasen - Hagedorn Res Inst, Gentofte, Denmark
Christian Dina - University of Lille
Anna Koettgen - Johns Hopkins University
Olivier Le Bacquer - Univ Lille 2, Inst Pasteur, CNRS, Unite Mixte Rech 8090, Lille, France
Francois Pattou - Univ Lille Nord France, INSERM, Lille, France
Jalal Taneera - Malmö University
Valgerdur Steinthorsdottir - deCODE Genet, Reykjavik, Iceland
Denis Rybin - Boston University
Kristin Ardlie
Michael Sampson - Norwich University
Lu Qi - Harvard University
Mandy van Hoek - College Station Medical Center
Michael N. Weedon - University of Exeter
Yurii S. Aulchenko - Biostat
Benjamin F. Voight - Massachusetts Institute of Technology
Harald Grallert - Helmholtz Zentrum Muenchen, Inst Epidemiol, Neuherberg, Germany
Beverley Balkau - Inserm
Richard N. Bergman - Supreme Council Of Health
Suzette J. Bielinski - College Station Medical Center
Amelie Bonnefond - Univ Lille 2, Inst Pasteur, CNRS, Unite Mixte Rech 8090, Lille, France
Lori L. Bonnycastle - NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA
Knut Borch-Johnsen - Steno Diabet Ctr, Copenhagen, Denmark
Yvonne Boettcher - College Station Medical Center
Eric Brunner - UCL, Dept Epidemiol & Publ Hlth, London, England
Thomas A. Buchanan - Supreme Council Of Health
Suzannah J. Bumpstead - Wellcome Sanger Institute
Christine Cavalcanti-Proenca - University of Lille
Guillaume Charpentier - Corbeil Essonnes Hosp, Endocrinol Diabetol Unit, Essonnes, France
Yii-Der Ida Chen - College Station Medical Center
Peter S. Chines - NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA
Francis S. Collins - NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA
Marilyn Cornelis - Harvard University
Gabriel J. Crawford - Massachusetts Institute of Technology
Jerome Delplanque - Univ Lille 2, Inst Pasteur, CNRS, Unite Mixte Rech 8090, Lille, France
Alex Doney - University of Dundee
Josephine M. Egan - NIA, Clin Invest Lab, Baltimore, MD 21224 USA
Michael R. Erdos - NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA
Mathieu Firmann - College Station Medical Center
Nita G. Forouhi - Massachusetts Rehabilitation Commission
Caroline S. Fox - Harvard University
Mark O. Goodarzi - College Station Medical Center
Juergen Graessler - College Station Medical Center
Aroon Hingorani - UCL, Dept Epidemiol & Publ Hlth, London, England
Bo Isomaa - Folkhalsan Res Ctr, Helsinki, Finland
Torben Jorgensen - Glostrup Univ Hosp, Res Ctr Prevent & Hlth, Glostrup, Denmark
Mika Kivimaki - UCL, Dept Epidemiol & Publ Hlth, London, England
Peter Kovacs - Univ Leipzig, Interdisciplinary Ctr Clin Res, Leipzig, Germany
Knut Krohn - Univ Leipzig, Interdisciplinary Ctr Clin Res, Leipzig, Germany
Meena Kumari - UCL, Dept Epidemiol & Publ Hlth, London, England
Torsten Lauritzen - Univ Aarhus, Dept Gen Practice, Aarhus, Denmark
Claire Levy-Marchal - Inserm
Vladimir Mayor - College Station Medical Center
Jarred B. McAteer - Massachusetts Institute of Technology
David Meyre - Univ Lille 2, Inst Pasteur, CNRS, Unite Mixte Rech 8090, Lille, France
Braxton D. Mitchell - Supreme Council Of Health
Karen L. Mohlke - Univ N Carolina, Dept Genet, Chapel Hill, NC USA
Mario A. Morken - NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA
Narisu Narisu - NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA
Colin N. A. Palmer - University of Dundee
Ruth Pakyz - Supreme Council Of Health
Laura Pascoe - College Station Medical Center
Felicity Payne - Wellcome Sanger Institute
Daniel Pearson - NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA
Wolfgang Rathmann - German Diabet Ctr, Inst Biometr & Epidemiol, Dusseldorf, Germany
Annelli Sandbaek - Univ Aarhus, Dept Gen Practice, Aarhus, Denmark
Avan Aihie Sayer - University of Southampton
Laura J. Scott - Biostat
Stephen J. Sharp - Massachusetts Rehabilitation Commission
Eric Sijbrands - College Station Medical Center
Andrew Singleton - NIA, Neurogenet Lab, Bethesda, MD 20892 USA
David S. Siscovick - University of Washington
Nicholas L. Smith - University of Washington
Thomas Sparso - Hagedorn Res Inst, Gentofte, Denmark
Amy J. Swift - NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA
Holly Syddall - University of Southampton
Gudmar Thorleifsson - deCODE Genet, Reykjavik, Iceland
Anke Toenjes - College Station Medical Center
Tiinamaija Tuomi - Folkhalsan Res Ctr, Helsinki, Finland
Jaakko Tuomilehto - University of Helsinki
Timo T. Valle - Natl Publ Hlth Inst, Dept Epidemiol & Hlth Promot, Helsinki, Finland
Gerard Waeber - College Station Medical Center
Andrew Walley - University of London
Dawn M. Waterworth - GlaxoSmithKline
Eleftheria Zeggini - Wellcome Sanger Institute
Jing Hua Zhao - Massachusetts Rehabilitation Commission
Thomas Illig - Helmholtz Zentrum Muenchen, Inst Epidemiol, Neuherberg, Germany
H. Erich Wichmann - Helmholtz Zentrum Muenchen, Inst Epidemiol, Neuherberg, Germany
James F. Wilson - University of Edinburgh
Cornelia van Duijn - College Station Medical Center
Frank B. Hu - Harvard University
Andrew D. Morris - University of Dundee
Timothy M. Frayling - University of Exeter
Andrew T. Hattersley - University of Exeter
Unnur Thorsteinsdottir - deCODE Genet, Reykjavik, Iceland
Kari Stefansson - University of Iceland
Peter Nilsson - Malmö University
Ann-Christine Syvanen - Uppsala University
Alan R. Shuldiner - Supreme Council Of Health
Mark Walker - College Station Medical Center
Stefan R. Bornstein - College Station Medical Center
Peter Schwarz - College Station Medical Center
Gordon H. Williams - Harvard University
David M. Nathan - Harvard University
Johanna Kuusisto - College Station Medical Center
Markku Laakso - College Station Medical Center
Cyrus Cooper - University of Southampton
Michael Marmot - UCL, Dept Epidemiol & Publ Hlth, London, England
Luigi Ferrucci - NIA, Clin Res Branch, Baltimore, MD 21224 USA
Vincent Mooser - GlaxoSmithKline
Michael Stumvoll - College Station Medical Center
Ruth J. F. Loos - Massachusetts Rehabilitation Commission
David Altshuler - Massachusetts Institute of Technology
Bruce M. Psaty - University of Washington
Jerome I. Rotter - College Station Medical Center
Eric Boerwinkle - Univ Texas Hlth Sci Ctr, Ctr Human Genet, Houston, TX USA
Torben Hansen - Hagedorn Res Inst, Gentofte, Denmark
Oluf Pedersen - Hagedorn Res Inst, Gentofte, Denmark
Jose C. Florez - Massachusetts Institute of Technology
Mark I. McCarthy - University of Oxford
Michael Boehnke - Biostat
Ines Barroso - Wellcome Sanger Institute
Robert Sladek - McGill University
Philippe Froguel - University of Lille
James B. Meigs - College Station Medical Center
Leif Groop - Malmö University
Nicholas J. Wareham - Massachusetts Rehabilitation Commission
Richard M. Watanabe - Supreme Council Of Health
GIANT Consortium
Publication Details: Nature genetics, Vol.42(2), pp.142-U75
Publisher: Springer Nature
Number of pages: 9
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Identifiers: 9937613708331
Academic Unit: King Abdulaziz University
Language: English
Resource Type: Journal article