No Interactions Between Previously Associated 2-Hour Glucose Gene Variants and Physical Activity or BMI on 2-Hour Glucose Levels

  1. Claudia Langenberg1
  1. 1Medical Research Council Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, United Kingdom
  2. 2Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts
  3. 3Department of Epidemiology, Johns Hopkins University, Baltimore, Maryland
  4. 4Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
  5. 5Hagedorn Research Institute, Gentofte, Denmark
  6. 6Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts
  7. 7Department of Medicine, Universite de Sherbrooke, Sherbrooke, Québec, Canada
  8. 8Genetic and Molecular Epidemiology Unit, Department of Clinical Sciences, Lund University, Malmö, Sweden
  9. 9Genetic Epidemiology and Clinical Research Group, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
  10. 10Department of Odontology, Umeå University, Umeå, Sweden
  11. 11Medical Department, University of Leipzig, Leipzig, Germany
  12. 12Integriertes Forschungs- und Behandlungszentrum (IFB) Adiposity Diseases, University of Leipzig, Leipzig, Germany
  13. 13Office of Public Health Genomics, Centers for Disease Control and Prevention, Atlanta, Georgia
  14. 14Centre National de la Recherche Scientifique (CNRS)-UMR-8199, Institut Pasteur de Lille, Lille, France
  15. 15University Lille Nord de France, Lille, France
  16. 16Department of Medicine–Preventive Medicine and Epidemiology, Boston University, Boston, Massachusetts
  17. 17Center for Statistical Genetics, Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, Michigan
  18. 18Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland
  19. 19Swiss Institute of Bionformatics, Lausanne, Switzerland
  20. 20Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom
  21. 21Oxford Centre for Diabetes, Endocrinology, and Metabolism, University of Oxford, Oxford, United Kingdom
  22. 22Department of Preventive Medicine, Northwestern University, Chicago, Illinois
  23. 23Clinical Research Branch, National Institute on Aging, Baltimore, Maryland
  24. 24Research Centre for Prevention and Health, Glostrup University Hospital, Glostrup, Denmark
  25. 25Institute of Genetic Medicine, Johns Hopkins University, Baltimore, Maryland
  26. 26Human Genetics Center, The University of Texas Health Science Center at Houston, Texas
  27. 27National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland
  28. 28Department of Medicine III, Medical Faculty Carl Gustav Carus, University of Dresden, Dresden, Germany
  29. 29University College London, Department of Epidemiology and Public Health, London, United Kingdom
  30. 30Wellcome Trust Sanger Institute, Hinxton, Cambdridge, United Kingdom
  31. 31Laboratory of Clinical Investigation, National Institute of Aging, Baltimore, Maryland
  32. 32Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California
  33. 33Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
  34. 34Medical Research Council Lifecourse Epidemiology Unit, University of Southampton, Southampton, United Kingdom
  35. 35National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts
  36. 36Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
  37. 37Division of Endocrinology, Diabetes and Metabolism; Cedars-Sinai Medical Center, Los Angeles, California
  38. 38Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
  39. 39Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
  40. 40Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark
  41. 41Infection, Inflammation and Immunity, University of Southampton, Southhampton, United Kingdom
  42. 42Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts
  43. 43Folkhälsan Research Center, Helsinki, and Department of Social Services and Health Care, Jakobstad, Finland
  44. 44Diabetes and Endocrinology Unit, Department of Clinical Sciences, Lund Univeristy, Malmö, Sweden
  45. 45Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
  46. 46Interdisciplinary Center for Clinical Research, University of Leipzig, Leipzig, Germany
  47. 47University of Eastern Finland, and Kuopio University Hospital, Kuopio, Finland
  48. 48INSERM CIC EC 05, Hôpital Robert Debré, Paris, France
  49. 49Cardiovascular Health Research Unit and Department of Medicine, University of Washington, Seattle, Washington
  50. 50Institute of Social and Preventive Medicine (IUMSP), Centre Hospitalier Universitaire Vaudois (CHUV), and University of Lausanne, Lausanne, Switzerland
  51. 51Institute for Medical Informatics and Biometry, Medical Faculty Carl Gustav Carus, University of Dresden, Dresden, Germany
  52. 52Department of Epidemiology and Carolina Center for Genome Sciences, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
  53. 53Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, Minnesota
  54. 54Metabolic Disease Group, Wellcome Trust Sanger Institute, Hinxton, Cambdridge, United Kingdom
  55. 55Departments of Epidemiology, Medicine, and Health Services, University of Washington, Seattle, Washington
  56. 56Group Health Research Institute, Group Health, Seattle, Washington
  57. 57Department of Biostatistics, University of Washington, Seattle, Washington
  58. 58Boston University Data Coordinating Center, Boston, Massachusetts
  59. 59Department of Medicine, Harvard Medical School, Boston, Massachusetts
  60. 60General Medicine Division, Massachusetts General Hospital, Boston, Massachusetts
  61. 61Cardiovascular Health Research Unit, Departments of Medicine and Epidemiology, University of Washington, Seattle, Washington
  62. 62Department of Internal Medicine, CHUV, Lausanne, Switzerland
  63. 63Brigham and Women's Hospital, Boston, Massachusetts
  64. 64Harvard Medical School, Boston, Massachusetts
  65. 65Steno Diabetes Center, Gentofte, Denmark
  66. 66Genetics of Complex Traits, Peninsula College of Medicine and Dentistry, Exeter, United Kingdom
  67. 67Botnar Research Centre, University of Oxford, Oxford, United Kingdom
  68. 68Department of Genomics of Common Disease, School of Public Health, Imperial College London, London, United Kingdom
  69. 69Institute of Cellular Medicine, Newcastle University, Newcastle, United Kingdom
  70. 70Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California
  71. 71Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California
  72. 72Institute of Biomedical Science, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
  73. 73Faculty of Health Sciences, University of Aarhus, Aarhus, Denmark
  74. 74University of Cambridge Metabolic Research Laboratories and NIHR Cambridge Biomedical Research Centre, Addenbrooke's Hospital, Cambridge, United Kingdom
  75. 75Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts
  76. 76Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts
  77. 77Diabetes Unit, Massachusetts General Hospital, Boston, Massachusetts
  1. Corresponding author: Robert A. Scott, robert.scott{at}mrc-epid.cam.ac.uk.
  1. 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

  • Received July 13, 2011.
  • Accepted January 11, 2012.

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.

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  1. Diabetes vol. 61 no. 5 1291-1296
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