Brief Communication abstract


Nature Genetics 39, 951 - 953 (2007)
Published online: 1 July 2007 | doi:10.1038/ng2067

Common variants in WFS1 confer risk of type 2 diabetes

Manjinder S Sandhu1,2,14, Michael N Weedon3,14, Katherine A Fawcett4, Jon Wasson5, Sally L Debenham2, Allan Daly4, Hana Lango3, Timothy M Frayling3, Rosalind J Neumann5, Richard Sherva5, Ilana Blech6, Paul D Pharoah7, Colin N A Palmer8, Charlotte Kimber8, Roger Tavendale8, Andrew D Morris9, Mark I McCarthy10,11, Mark Walker12, Graham Hitman13, Benjamin Glaser6, M Alan Permutt5, Andrew T Hattersley3, Nicholas J Wareham1 & Inês Barroso4

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We studied genes involved in pancreatic beta cell function and survival, identifying associations between SNPs in WFS1 and diabetes risk in UK populations that we replicated in an Ashkenazi population and in additional UK studies. In a pooled analysis comprising 9,533 cases and 11,389 controls, SNPs in WFS1 were strongly associated with diabetes risk. Rare mutations in WFS1 cause Wolfram syndrome; using a gene-centric approach, we show that variation in WFS1 also predisposes to common type 2 diabetes.

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  1. UK Medical Research Council (MRC) Epidemiology Unit, Strangeways Research Laboratory, Cambridge CB1 8RN, UK.
  2. Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge, Cambridge CB2 0SR, UK.
  3. Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter EX1 2LU, UK.
  4. Metabolic Disease Group, Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
  5. Washington University School of Medicine, St. Louis, Missouri 63110, USA.
  6. Endocrine and Metabolism Service, The Hadassah Hebrew University Medical Center, Jerusalem 91120, Israel.
  7. Cancer Research UK Department of Oncology, Strangeways Research Laboratory, University of Cambridge, Cambridge CB1 8RN, UK.
  8. Population Pharmacogenetics Group, Biomedical Research Centre, University of Dundee, Dundee DD1 9SY, UK.
  9. Diabetes Research Group, Division of Medicine and Therapeutics, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, UK.
  10. Oxford Centre for Diabetes, Endocrinology and Metabolism, Oxford OX3 7LJ, UK.
  11. Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
  12. Diabetes Research Group, School of Clinical Medical Sciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
  13. Centre for Diabetes and Metabolic Medicine, Barts and the London, Queen Mary's School of Medicine and Dentistry, University of London, London E1 1BB, UK.
  14. These authors contributed equally to this work.

Correspondence to: Inês Barroso4 e-mail: ib1@sanger.ac.uk

Correspondence to: Manjinder S Sandhu1,2,14 e-mail: manj.sandhu@srl.cam.ac.uk