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; 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

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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

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: Richa Saxena - Broad Institute
Marie-France Hivert - College Station Medical Center
Claudia Langenberg - MRC Epidemiology Unit
Toshiko Tanaka - MedStar Health
James S. Pankow - University of Minnesota
Peter Vollenweider - University Hospital of Lausanne
Valeriya Lyssenko - Lund University
Nabila Bouatia-Naji - Université de Lille
Josee Dupuis - Boston University
Anne U. Jackson - University of Michigan–Ann Arbor
W. H. Linda Kao - Johns Hopkins University
Man Li - Boston University
Nicole L. Glazer - University of Washington
Alisa K. Manning - Boston University
Jian'an Luan - Massachusetts Rehabilitation Commission
Heather M. Stringham - University of Michigan–Ann Arbor
Inga Prokopenko - Oxford Centre for Diabetes, Endocrinology and Metabolism
Toby Johnson - University of Lausanne
Niels Grarup - Hagedorn Res Inst, Gentofte, Denmark
Trine W. Boesgaard - Hagedorn Res Inst, Gentofte, Denmark
Cecile Lecoeur - Université de Lille
Peter Shrader - Massachusetts General Hospital
Jeffrey O'Connell - Supreme Council Of Health
Erik Ingelsson - Karolinska Institutet
David J. Couper - University of North Carolina at Chapel Hill
Kenneth Rice - University of Washington
Kijoung Song - GlaxoSmithKline
Camilla H. Andreasen - Hagedorn Res Inst, Gentofte, Denmark
Christian Dina - Institut Pasteur de Lille
Anna Koettgen - Johns Hopkins University
Olivier Le Bacquer - Institut Pasteur de Lille
Francois Pattou - Université Lille Nord de France
Jalal Taneera - Lund University
Valgerdur Steinthorsdottir - deCODE Genet, Reykjavik, Iceland
Denis Rybin - Boston University
Kristin Ardlie - Broad Institute
Michael Sampson - Norfolk and Norwich University Hospital
Lu Qi - Harvard University
Mandy van Hoek - Erasmus MC
Michael N. Weedon - University of Exeter
Yurii S. Aulchenko - Erasmus MC
Benjamin F. Voight - Center for Human Genetics
Harald Grallert - Helmholtz Zentrum München
Beverley Balkau - Université Paris-Sud
Richard N. Bergman - University of Southern California
Suzette J. Bielinski - Mayo Clinic
Amelie Bonnefond - Institut Pasteur de Lille
Lori L. Bonnycastle - National Human Genome Research Institute
Knut Borch-Johnsen - Steno Diabet Ctr, Copenhagen, Denmark
Yvonne Boettcher - College Station Medical Center
Eric Brunner - University College London
Thomas A. Buchanan - University of Southern California
Suzannah J. Bumpstead - Wellcome Sanger Institute
Christine Cavalcanti-Proenca - Institut Pasteur de Lille
Guillaume Charpentier - Corbeil Essonnes Hosp, Endocrinol Diabetol Unit, Essonnes, France
Yii-Der Ida Chen - Cedars-Sinai Medical Center
Peter S. Chines - National Human Genome Research Institute
Francis S. Collins - National Human Genome Research Institute
Marilyn Cornelis - Harvard University
Gabriel J. Crawford - Broad Institute
Jerome Delplanque - Institut Pasteur de Lille
Alex Doney - University of Dundee
Josephine M. Egan - National Institute on Aging
Michael R. Erdos - National Human Genome Research Institute
Mathieu Firmann - University Hospital of Lausanne
Nita G. Forouhi - Medical Research Council
Caroline S. Fox - Brigham and Women's Hospital
Mark O. Goodarzi - Cedars-Sinai Medical Center
Juergen Graessler - TU Dresden
Aroon Hingorani - University College London
Bo Isomaa - Folkhälsans Forskningscentrum
Torben Jorgensen - Glostrup Univ Hosp, Res Ctr Prevent & Hlth, Glostrup, Denmark
Mika Kivimaki - University College London
Peter Kovacs - Univ Leipzig, Interdisciplinary Ctr Clin Res, Leipzig, Germany
Knut Krohn - Univ Leipzig, Interdisciplinary Ctr Clin Res, Leipzig, Germany
Meena Kumari - University College London
Torsten Lauritzen - Aarhus University
Claire Levy-Marchal - Inserm
Vladimir Mayor - University Hospital of Lausanne
Jarred B. McAteer - Massachusetts General Hospital
David Meyre - Université de Lille
Braxton D. Mitchell - University of Maryland, Baltimore
Karen L. Mohlke - University of North Carolina at Chapel Hill
Mario A. Morken - National Human Genome Research Institute
Narisu Narisu - National Human Genome Research Institute
Colin N. A. Palmer - University of Dundee
Ruth Pakyz - University of Maryland, Baltimore
Laura Pascoe - Cellular Therapeutics
Felicity Payne - Wellcome Sanger Institute
Daniel Pearson - National Human Genome Research Institute
Wolfgang Rathmann - Deutsches Diabetes-Zentrum e.V.
Annelli Sandbaek - Univ Aarhus, Dept Gen Practice, Aarhus, Denmark
Avan Aihie Sayer - University of Southampton
Laura J. Scott - University of Michigan–Ann Arbor
Stephen J. Sharp - Medical Research Council
Eric Sijbrands - College Station Medical Center
Andrew Singleton - National Institute on Aging
David S. Siscovick - University of Washington
Nicholas L. Smith - University of Washington
Thomas Sparso - Hagedorn Res Inst, Gentofte, Denmark
GIANT Consortium
Publication Details: Nature genetics, Vol.42(2), pp.142-U75
Publisher: Springer Nature
Number of pages: 9
Date published: 01/02/2010
Grant note: U01 HG004399; U01 HG004402-02; U01 HG004399-02; U01 HG004402 / NHGRI NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI) M01RR016500 / NATIONAL CENTER FOR RESEARCH RESOURCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Research Resources (NCRR) M01 RR000052; M01 RR016500; M01 RR001066-26; M01 RR000052-46; M01 RR016500-08; M01 RR001066 / NCRR NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Research Resources (NCRR) MC_U106188470 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) U01HG004402 / NATIONAL HUMAN GENOME RESEARCH INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI) ZIAAG001050 / NATIONAL INSTITUTE ON AGING; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA) P01 CA087969-12; P01 CA087969 / NCI NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) NF-SI-0508-10082 / National Institute for Health Research; National Institute for Health Research (NIHR) 088885; 077016 / Wellcome Trust; European Commission U1475000001 / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC); European Commission
Identifiers: 99926669602346
Academic Unit: School of Biosciences
Language: English
Resource Type: Journal article

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

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