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A genome-wide association study identifies novel risk loci for type 2 diabetes

Author

Listed:
  • Robert Sladek

    (Departments of Human Genetics,
    Medicine and,
    McGill University and Genome Quebec Innovation Centre, Montreal H3A 1A4, Canada)

  • Ghislain Rocheleau

    (Departments of Human Genetics,)

  • Johan Rung

    (McGill University and Genome Quebec Innovation Centre, Montreal H3A 1A4, Canada)

  • Christian Dina

    (CNRS 8090-Institute of Biology, Pasteur Institute, Lille 59019 Cedex, France)

  • Lishuang Shen

    (Departments of Human Genetics,)

  • David Serre

    (Departments of Human Genetics,)

  • Philippe Boutin

    (CNRS 8090-Institute of Biology, Pasteur Institute, Lille 59019 Cedex, France)

  • Daniel Vincent

    (McGill University and Genome Quebec Innovation Centre, Montreal H3A 1A4, Canada)

  • Alexandre Belisle

    (McGill University and Genome Quebec Innovation Centre, Montreal H3A 1A4, Canada)

  • Samy Hadjadj

    (Endocrinology and Diabetology, University Hospital, Poitiers 86021 Cedex, France)

  • Beverley Balkau

    (INSERM U780-IFR69, Villejuif 94807, France)

  • Barbara Heude

    (INSERM U780-IFR69, Villejuif 94807, France)

  • Guillaume Charpentier

    (Endocrinology-Diabetology Unit, Corbeil-Essonnes Hospital, Corbeil-Essonnes 91100, France)

  • Thomas J. Hudson

    (McGill University and Genome Quebec Innovation Centre, Montreal H3A 1A4, Canada
    Ontario Institute for Cancer Research, Toronto M5G 1L7, Canada)

  • Alexandre Montpetit

    (McGill University and Genome Quebec Innovation Centre, Montreal H3A 1A4, Canada)

  • Alexey V. Pshezhetsky

    (Montreal Diabetes Research Center, Montreal H2L 4M1, Canada)

  • Marc Prentki

    (Montreal Diabetes Research Center, Montreal H2L 4M1, Canada
    University of Montreal and the Centre Hospitalier de l’Université de Montréal, Montreal H3C 3J7, Canada)

  • Barry I. Posner

    (Medicine and,
    Montreal H3A 2B2, Canada)

  • David J. Balding

    (Imperial College, St Mary’s Campus, Norfolk Place, London W2 1PG, UK)

  • David Meyre

    (CNRS 8090-Institute of Biology, Pasteur Institute, Lille 59019 Cedex, France)

  • Constantin Polychronakos

    (Departments of Human Genetics,
    Pediatrics, Faculty of Medicine, McGill University, Montreal H3H 1P3, Canada)

  • Philippe Froguel

    (CNRS 8090-Institute of Biology, Pasteur Institute, Lille 59019 Cedex, France
    Section of Genomic Medicine, Imperial College London W12 0NN, and Hammersmith Hospital, Du Cane Road, London W12 0HS, UK)

Abstract

Type 2 diabetes mellitus results from the interaction of environmental factors with a combination of genetic variants, most of which were hitherto unknown. A systematic search for these variants was recently made possible by the development of high-density arrays that permit the genotyping of hundreds of thousands of polymorphisms. We tested 392,935 single-nucleotide polymorphisms in a French case–control cohort. Markers with the most significant difference in genotype frequencies between cases of type 2 diabetes and controls were fast-tracked for testing in a second cohort. This identified four loci containing variants that confer type 2 diabetes risk, in addition to confirming the known association with the TCF7L2 gene. These loci include a non-synonymous polymorphism in the zinc transporter SLC30A8, which is expressed exclusively in insulin-producing β-cells, and two linkage disequilibrium blocks that contain genes potentially involved in β-cell development or function (IDE–KIF11–HHEX and EXT2–ALX4). These associations explain a substantial portion of disease risk and constitute proof of principle for the genome-wide approach to the elucidation of complex genetic traits.

Suggested Citation

  • Robert Sladek & Ghislain Rocheleau & Johan Rung & Christian Dina & Lishuang Shen & David Serre & Philippe Boutin & Daniel Vincent & Alexandre Belisle & Samy Hadjadj & Beverley Balkau & Barbara Heude &, 2007. "A genome-wide association study identifies novel risk loci for type 2 diabetes," Nature, Nature, vol. 445(7130), pages 881-885, February.
    • Handle: RePEc:nat:nature:v:445:y:2007:i:7130:d:10.1038_nature05616
    DOI: 10.1038/nature05616
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