No Interactions Between Previously Associated 2-Hour Glucose Gene Variants and Physical Activity or BMI on 2-Hour Glucose Levels
- Robert A. Scott1⇓,
- Audrey Y. Chu2,3,
- Niels Grarup4,5,
- Alisa K. Manning6,
- Marie-France Hivert7,
- Dmitry Shungin8,9,10,
- Anke Tönjes11,12,
- Ajay Yesupriya13,
- Daniel Barnes1,
- Nabila Bouatia-Naji14,15,
- Nicole L. Glazer16,
- Anne U. Jackson17,
- Zoltán Kutalik18,19,
- Vasiliki Lagou20,21,
- Diana Marek18,19,
- Laura J. Rasmussen-Torvik22,
- Heather M. Stringham17,
- Toshiko Tanaka23,
- Mette Aadahl24,
- Dan E. Arking25,
- Sven Bergmann18,19,
- Eric Boerwinkle26,
- Lori L. Bonnycastle27,
- Stefan R. Bornstein28,
- Eric Brunner29,
- Suzannah J. Bumpstead30,
- Soren Brage1,
- Olga D. Carlson31,
- Han Chen6,
- Yii-Der Ida Chen32,
- Peter S. Chines27,
- Francis S. Collins27,
- David J. Couper33,
- Elaine M. Dennison34,
- Nicole F. Dowling13,
- Josephine S. Egan31,
- Ulf Ekelund1,
- Michael R. Erdos27,
- Nita G. Forouhi1,
- Caroline S. Fox35,36,
- Mark O. Goodarzi32,37,
- Jürgen Grässler28,
- Stefan Gustafsson38,
- Göran Hallmans39,
- Torben Hansen4,5,40,
- Aroon Hingorani29,
- John W. Holloway41,
- Frank B. Hu42,
- Bo Isomaa43,
- Karen A. Jameson34,
- Ingegerd Johansson10,
- Anna Jonsson44,
- Torben Jørgensen24,45,
- Mika Kivimaki29,
- Peter Kovacs46,
- Meena Kumari29,
- Johanna Kuusisto47,
- Markku Laakso47,
- Cécile Lecoeur14,15,
- Claire Lévy-Marchal15,48,
- Guo Li49,
- Ruth J.F. Loos1,
- Valeri Lyssenko44,
- Michael Marmot29,
- Pedro Marques-Vidal50,
- Mario A. Morken27,
- Gabriele Müller51,
- Kari E. North52,
- James S. Pankow53,
- Felicity Payne54,
- Inga Prokopenko20,21,
- Bruce M. Psaty55,56,
- Frida Renström8,42,
- Ken Rice57,
- Jerome I. Rotter32,
- Denis Rybin58,
- Camilla H. Sandholt4,5,
- Avan A. Sayer34,
- Peter Shrader59,60,
- Peter E.H. Schwarz28,
- David S. Siscovick61,
- Alena Stančáková47,
- Michael Stumvoll11,12,
- Tanya M. Teslovich17,
- Gérard Waeber62,
- Gordon H. Williams63,64,
- Daniel R. Witte65,
- Andrew R. Wood66,
- Weijia Xie66,
- Michael Boehnke17,
- Cyrus Cooper34,67,
- Luigi Ferrucci23,
- Philippe Froguel14,15,68,
- Leif Groop44,
- W.H. Linda Kao3,
- Peter Vollenweider62,
- Mark Walker69,
- Richard M. Watanabe70,71,
- Oluf Pedersen4,5,72,73,
- James B. Meigs59,60,
- Erik Ingelsson38,
- Inês Barroso54,74,
- Jose C. Florez59,75,76,77,
- Paul W. Franks8,9,42,
- Josée Dupuis6,35,
- Nicholas J. Wareham1 and
- Claudia Langenberg1
- 1Medical Research Council Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, United Kingdom
- 2Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts
- 3Department of Epidemiology, Johns Hopkins University, Baltimore, Maryland
- 4Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
- 5Hagedorn Research Institute, Gentofte, Denmark
- 6Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts
- 7Department of Medicine, Universite de Sherbrooke, Sherbrooke, Québec, Canada
- 8Genetic and Molecular Epidemiology Unit, Department of Clinical Sciences, Lund University, Malmö, Sweden
- 9Genetic Epidemiology and Clinical Research Group, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
- 10Department of Odontology, Umeå University, Umeå, Sweden
- 11Medical Department, University of Leipzig, Leipzig, Germany
- 12Integriertes Forschungs- und Behandlungszentrum (IFB) Adiposity Diseases, University of Leipzig, Leipzig, Germany
- 13Office of Public Health Genomics, Centers for Disease Control and Prevention, Atlanta, Georgia
- 14Centre National de la Recherche Scientifique (CNRS)-UMR-8199, Institut Pasteur de Lille, Lille, France
- 15University Lille Nord de France, Lille, France
- 16Department of Medicine–Preventive Medicine and Epidemiology, Boston University, Boston, Massachusetts
- 17Center for Statistical Genetics, Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, Michigan
- 18Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland
- 19Swiss Institute of Bionformatics, Lausanne, Switzerland
- 20Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom
- 21Oxford Centre for Diabetes, Endocrinology, and Metabolism, University of Oxford, Oxford, United Kingdom
- 22Department of Preventive Medicine, Northwestern University, Chicago, Illinois
- 23Clinical Research Branch, National Institute on Aging, Baltimore, Maryland
- 24Research Centre for Prevention and Health, Glostrup University Hospital, Glostrup, Denmark
- 25Institute of Genetic Medicine, Johns Hopkins University, Baltimore, Maryland
- 26Human Genetics Center, The University of Texas Health Science Center at Houston, Texas
- 27National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland
- 28Department of Medicine III, Medical Faculty Carl Gustav Carus, University of Dresden, Dresden, Germany
- 29University College London, Department of Epidemiology and Public Health, London, United Kingdom
- 30Wellcome Trust Sanger Institute, Hinxton, Cambdridge, United Kingdom
- 31Laboratory of Clinical Investigation, National Institute of Aging, Baltimore, Maryland
- 32Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California
- 33Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
- 34Medical Research Council Lifecourse Epidemiology Unit, University of Southampton, Southampton, United Kingdom
- 35National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts
- 36Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
- 37Division of Endocrinology, Diabetes and Metabolism; Cedars-Sinai Medical Center, Los Angeles, California
- 38Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
- 39Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
- 40Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark
- 41Infection, Inflammation and Immunity, University of Southampton, Southhampton, United Kingdom
- 42Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts
- 43Folkhälsan Research Center, Helsinki, and Department of Social Services and Health Care, Jakobstad, Finland
- 44Diabetes and Endocrinology Unit, Department of Clinical Sciences, Lund Univeristy, Malmö, Sweden
- 45Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
- 46Interdisciplinary Center for Clinical Research, University of Leipzig, Leipzig, Germany
- 47University of Eastern Finland, and Kuopio University Hospital, Kuopio, Finland
- 48INSERM CIC EC 05, Hôpital Robert Debré, Paris, France
- 49Cardiovascular Health Research Unit and Department of Medicine, University of Washington, Seattle, Washington
- 50Institute of Social and Preventive Medicine (IUMSP), Centre Hospitalier Universitaire Vaudois (CHUV), and University of Lausanne, Lausanne, Switzerland
- 51Institute for Medical Informatics and Biometry, Medical Faculty Carl Gustav Carus, University of Dresden, Dresden, Germany
- 52Department of Epidemiology and Carolina Center for Genome Sciences, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
- 53Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, Minnesota
- 54Metabolic Disease Group, Wellcome Trust Sanger Institute, Hinxton, Cambdridge, United Kingdom
- 55Departments of Epidemiology, Medicine, and Health Services, University of Washington, Seattle, Washington
- 56Group Health Research Institute, Group Health, Seattle, Washington
- 57Department of Biostatistics, University of Washington, Seattle, Washington
- 58Boston University Data Coordinating Center, Boston, Massachusetts
- 59Department of Medicine, Harvard Medical School, Boston, Massachusetts
- 60General Medicine Division, Massachusetts General Hospital, Boston, Massachusetts
- 61Cardiovascular Health Research Unit, Departments of Medicine and Epidemiology, University of Washington, Seattle, Washington
- 62Department of Internal Medicine, CHUV, Lausanne, Switzerland
- 63Brigham and Women's Hospital, Boston, Massachusetts
- 64Harvard Medical School, Boston, Massachusetts
- 65Steno Diabetes Center, Gentofte, Denmark
- 66Genetics of Complex Traits, Peninsula College of Medicine and Dentistry, Exeter, United Kingdom
- 67Botnar Research Centre, University of Oxford, Oxford, United Kingdom
- 68Department of Genomics of Common Disease, School of Public Health, Imperial College London, London, United Kingdom
- 69Institute of Cellular Medicine, Newcastle University, Newcastle, United Kingdom
- 70Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California
- 71Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California
- 72Institute of Biomedical Science, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
- 73Faculty of Health Sciences, University of Aarhus, Aarhus, Denmark
- 74University of Cambridge Metabolic Research Laboratories and NIHR Cambridge Biomedical Research Centre, Addenbrooke's Hospital, Cambridge, United Kingdom
- 75Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts
- 76Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts
- 77Diabetes Unit, Massachusetts General Hospital, Boston, Massachusetts
- Corresponding author: Robert A. Scott, robert.scott{at}mrc-epid.cam.ac.uk.
-
R.A.S. and A.Y.C. contributed equally to this work.
Abstract
Gene–lifestyle interactions have been suggested to contribute to the development of type 2 diabetes. Glucose levels 2 h after a standard 75-g glucose challenge are used to diagnose diabetes and are associated with both genetic and lifestyle factors. However, whether these factors interact to determine 2-h glucose levels is unknown. We meta-analyzed single nucleotide polymorphism (SNP) × BMI and SNP × physical activity (PA) interaction regression models for five SNPs previously associated with 2-h glucose levels from up to 22 studies comprising 54,884 individuals without diabetes. PA levels were dichotomized, with individuals below the first quintile classified as inactive (20%) and the remainder as active (80%). BMI was considered a continuous trait. Inactive individuals had higher 2-h glucose levels than active individuals (β = 0.22 mmol/L [95% CI 0.13–0.31], P = 1.63 × 10−6). All SNPs were associated with 2-h glucose (β = 0.06–0.12 mmol/allele, P ≤ 1.53 × 10−7), but no significant interactions were found with PA (P > 0.18) or BMI (P ≥ 0.04). In this large study of gene–lifestyle interaction, we observed no interactions between genetic and lifestyle factors, both of which were associated with 2-h glucose. It is perhaps unlikely that top loci from genome-wide association studies will exhibit strong subgroup-specific effects, and may not, therefore, make the best candidates for the study of interactions.
Footnotes
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This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db11-0973/-/DC1.
- Received July 13, 2011.
- Accepted January 11, 2012.
- © 2012 by the American Diabetes Association.
Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
