Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Genetic variant near IRS1 is associated with type 2 diabetes, insulin resistance and hyperinsulinemia

Nature Genetics volume 41, pages 1110–1115 (2009)Cite this article

An Erratum to this article was published on 01 October 2009

This article has been updated

Abstract

Genome-wide association studies have identified common variants that only partially explain the genetic risk for type 2 diabetes (T2D). Using genome-wide association data from 1,376 French individuals, we identified 16,360 SNPs nominally associated with T2D and studied these SNPs in an independent sample of 4,977 French individuals. We then selected the 28 best hits for replication in 7,698 Danish subjects and identified 4 SNPs showing strong association with T2D, one of which (rs2943641, P = 9.3 × 10−12, OR = 1.19) was located adjacent to the insulin receptor substrate 1 gene (IRS1). Unlike previously reported T2D risk loci, which predominantly associate with impaired beta cell function, the C allele of rs2943641 was associated with insulin resistance and hyperinsulinemia in 14,358 French, Danish and Finnish participants from population-based cohorts; this allele was also associated with reduced basal levels of IRS1 protein and decreased insulin induction of IRS1-associated phosphatidylinositol-3-OH kinase activity in human skeletal muscle biopsies.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Experimental plan.
Figure 2: Association of rs2943641 with skeletal muscle IRS1 protein expression and IRS1-associated PI(3)K activity.

Similar content being viewed by others

Change history

  • 13 September 2009

    NOTE: In the version of this article initially published online, there were errors in the e-mail addresses of two of the corresponding authors. The correct e-mail address for Robert Sladek is robert.sladek@mcgill.ca; the correct e-mail address for Philippe Froguel is philippe.froguel@good.ibl.fr. These errors have been corrected for the print, PDF and HTML versions of this article.

References

  1. Stumvoll, M., Goldstein, B.J. & van Haeften, T.W. Type 2 diabetes: principles of pathogenesis and therapy. Lancet 365, 1333–1346 (2005).

    Article  CAS  PubMed  Google Scholar 

  2. Bouatia-Naji, N. I A variant near MTNR1B is associated with increased fasting plasma glucose levels and type 2 diabetes risk. Nat. Genet. 41, 89–94 (2009).

    Article  CAS  PubMed  Google Scholar 

  3. Saxena, R. et al. Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels. Science 316, 1331–1336 (2007).

    Article  CAS  PubMed  Google Scholar 

  4. Scott, L.J. et al. A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants. Science 316, 1341–1345 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Sladek, R. et al. A genome-wide association study identifies novel risk loci for type 2 diabetes. Nature 445, 881–885 (2007).

    Article  CAS  PubMed  Google Scholar 

  6. Steinthorsdottir, V. et al. A variant in CDKAL1 influences insulin response and risk of type 2 diabetes. Nat. Genet. 39, 770–775 (2007).

    Article  CAS  PubMed  Google Scholar 

  7. Unoki, H. et al. SNPs in KCNQ1 are associated with susceptibility to type 2 diabetes in East Asian and European populations. Nat. Genet. 40, 1098–1102 (2008).

    Article  CAS  PubMed  Google Scholar 

  8. Yasuda, K. et al. Variants in KCNQ1 are associated with susceptibility to type 2 diabetes mellitus. Nat. Genet. 40, 1092–1097 (2008).

    Article  CAS  PubMed  Google Scholar 

  9. Zeggini, E. et al. Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes. Nat. Genet. 40, 638–645 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Zeggini, E. et al. Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes. Science 316, 1336–1341 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Easton, D.F. et al. Genome-wide association study identifies novel breast cancer susceptibility loci. Nature 447, 1087–1093 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Sakamoto, H. et al. Genetic variation in PSCA is associated with susceptibility to diffuse-type gastric cancer. Nat. Genet. 40, 730–740 (2008).

    Article  CAS  PubMed  Google Scholar 

  13. Thomas, G. et al. Multiple loci identified in a genome-wide association study of prostate cancer. Nat. Genet. 40, 310–315 (2008).

    Article  CAS  PubMed  Google Scholar 

  14. Price, A.L. et al. Principal components analysis corrects for stratification in genome-wide association studies. Nat. Genet. 38, 904–909 (2006).

    Article  CAS  PubMed  Google Scholar 

  15. Pritchard, J.K., Stephens, M. & Donnelly, P. Inference of population structure using multilocus genotype data. Genetics 155, 945–959 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Samani, N.J. et al. Genomewide association analysis of coronary artery disease. N. Engl. J. Med. 357, 443–453 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Barrett, J.C. et al. Genome-wide association defines more than 30 distinct susceptibility loci for Crohn?s disease. Nat. Genet. 40, 955–962 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Gudmundsson, J. et al. Two variants on chromosome 17 confer prostate cancer risk, and the one in TCF2 protects against type 2 diabetes. Nat. Genet. 39, 977–983 (2007).

    Article  CAS  PubMed  Google Scholar 

  19. Balkau, B. An epidemiologic survey from a network of French Health Examination Centres, (D.E.S.I.R.): epidemiologic data on the insulin resistance syndrome. Rev. Epidemiol. Sante Publique 44, 373–375 (1996).

    CAS  PubMed  Google Scholar 

  20. Järvelin, M.R. et al. Ecological and individual predictors of birthweight in a northern Finland birth cohort 1986. Paediatr. Perinat. Epidemiol. 11, 298–312 (1997).

    Article  PubMed  Google Scholar 

  21. Jørgensen, T. et al. A randomized non-pharmacological intervention study for prevention of ischaemic heart disease: baseline results Inter99. Eur. J. Cardiovasc. Prev. Rehabil. 10, 377–386 (2003).

    Article  PubMed  Google Scholar 

  22. Alberti, K.G. & Zimmet, P.Z. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet. Med. 15, 539–553 (1998).

    Article  CAS  PubMed  Google Scholar 

  23. Poulsen, P. et al. Impact of genetic versus environmental factors on the control of muscle glycogen synthase activation in twins. Diabetes 54, 1289–1296 (2005).

    Article  CAS  PubMed  Google Scholar 

  24. Aston-Mourney, K., Proietto, J., Morahan, G. & Andrikopoulos, S. Too much of a good thing: why it is bad to stimulate the beta cell to secrete insulin. Diabetologia 51, 540–545 (2008).

    Article  CAS  PubMed  Google Scholar 

  25. Nandi, A., Kitamura, Y., Kahn, C.R. & Accili, D. Mouse models of insulin resistance. Physiol. Rev. 84, 623–647 (2004).

    Article  CAS  PubMed  Google Scholar 

  26. Tamemoto, H. et al. Insulin resistance and growth retardation in mice lacking insulin receptor substrate-1. Nature 372, 182–186 (1994).

    Article  CAS  PubMed  Google Scholar 

  27. Araki, E. et al. Alternative pathway of insulin signalling in mice with targeted disruption of the IRS-1 gene. Nature 372, 186–190 (1994).

    Article  CAS  PubMed  Google Scholar 

  28. Terauchi, Y. et al. Development of non-insulin-dependent diabetes mellitus in the double knockout mice with disruption of insulin receptor substrate-1 and beta cell glucokinase genes. Genetic reconstitution of diabetes as a polygenic disease. J. Clin. Invest. 99, 861–866 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Withers, D.J. et al. Disruption of IRS-2 causes type 2 diabetes in mice. Nature 391, 900–904 (1998).

    Article  CAS  PubMed  Google Scholar 

  30. Almind, K. et al. Amino acid polymorphisms of insulin receptor substrate-1 in non-insulin-dependent diabetes mellitus. Lancet 342, 828–832 (1993).

    Article  CAS  PubMed  Google Scholar 

  31. Almind, K., Inoue, G., Pedersen, O. & Kahn, C.R. A common amino acid polymorphism in insulin receptor substrate-1 causes impaired insulin signaling. Evidence from transfection studies. J. Clin. Invest. 97, 2569–2575 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Clausen, J.O. et al. Insulin resistance: interactions between obesity and a common variant of insulin receptor substrate-1. Lancet 346, 397–402 (1995).

    Article  CAS  PubMed  Google Scholar 

  33. Sesti, G. et al. Defects of the insulin receptor substrate (IRS) system in human metabolic disorders. FASEB J. 15, 2099–2111 (2001).

    Article  CAS  PubMed  Google Scholar 

  34. Florez, J.C. et al. Association testing of common variants in the insulin receptor substrate-1 gene (IRS1) with type 2 diabetes. Diabetologia 50, 1209–1217 (2007).

    Article  CAS  PubMed  Google Scholar 

  35. Florez, J.C. et al. Association testing in 9,000 people fails to confirm the association of the insulin receptor substrate-1 G972R polymorphism with type 2 diabetes. Diabetes 53, 3313–3318 (2004).

    Article  CAS  PubMed  Google Scholar 

  36. Jellema, A., Zeegers, M.P., Feskens, E.J., Dagnelie, P.C. & Mensink, R.P. Gly972Arg variant in the insulin receptor substrate-1 gene and association with type 2 diabetes: a meta-analysis of 27 studies. Diabetologia 46, 990–995 (2003).

    Article  CAS  PubMed  Google Scholar 

  37. Zeggini, E. et al. Association studies of insulin receptor substrate 1 gene (IRS1) variants in type 2 diabetes samples enriched for family history and early age of onset. Diabetes 53, 3319–3322 (2004).

    Article  CAS  PubMed  Google Scholar 

  38. Skol, A.D., Scott, L.J., Abecasis, G.R. & Boehnke, M. Optimal designs for two-stage genome-wide association studies. Genet. Epidemiol. 31, 776–788 (2007).

  39. Lauritzen, T. et al. The ADDITION study: proposed trial of the cost-effectiveness of an intensive multifactorial intervention on morbidity and mortality among people with type 2 diabetes detected by screening. Int. J. Obes.Relat. Metab. Disord. 24 (suppl. 3), S6–S11 (2000).

    Article  PubMed  Google Scholar 

  40. Purcell, S. et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am. J. Hum. Genet. 81, 559–575 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Poulsen, P. et al. Heritability of insulin secretion, peripheral and hepatic insulin action, and intracellular glucose partitioning in young and old Danish twins. Diabetes 54, 275–283 (2005).

    Article  CAS  PubMed  Google Scholar 

  42. Højlund, K. et al. Increased phosphorylation of skeletal muscle glycogen synthase at NH2-terminal sites during physiological hyperinsulinemia in type 2 diabetes. Diabetes 52, 1393–1402 (2003).

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

This work was funded by Genome Canada, Génome Québec and the Canada Foundation for Innovation. This work was also supported by the French Government (Agence Nationale de la Recherche), the French Region of Nord Pas De Calais (Contrat de Projets État-Région), and the following charities: Association Française des Diabétiques, Programme National de Recherche sur le Diabète and Association de Langue Française pour l'Etude du Diabète et des Maladies Métaboliques. The D.E.S.I.R. study has been supported by the Caisse Nationale d?Assurance Maladie des Travailleurs Salariés, Lilly, Novartis Pharma and Sanofi-Aventis, Institut National de la Santé et de la Recherche Médicale (INSERM) (Réseaux en Santé Publique, Interactions entre les déterminants de la santé), Association Diabète Risque Vasculaire, Fédération Française de Cardiologie, Fondation de France, Association de Langue Francaise pour l'Etude du Diabete et des Maladies Metaboliques, Office National Interprofessionnel des Vins, Ardix Medical, Bayer Diagnostics, Becton Dickinson, Cardionics, Merck Santé, Novo Nordisk, Pierre Fabre, Roche and Topcon. The D.E.S.I.R. Study Group: INSERM U780: B. Balkau, P. Ducimetière, E. Eschwège; INSERM U367: F. Alhenc-Gelas; Centre Hospitalier Universitaire D'Angers: Y. Gallois, A. Girault; Bichat Hospital: F. Fumeron, M. Marre; Medical Examination Services: Alençon, Angers, Caen, Chateauroux, Cholet, Le Mans and Tours; Research Institute for General Medicine: J. Cogneau; General practitioners of the region; Cross-Regional Institute for Health: C. Born, E. Caces, M. Cailleau, J.G. Moreau, F. Rakotozafy, J. Tichet, S. Vol. The NFBC 1986 study has been supported by the Oulu University Hospital, Finland, the Academy of Finland and the European Commission (Framework 5 award QLG1-CT-2000-01643). The Danish study was supported by grants from the Lundbeck Foundation Centre of Applied Medical Genomics for Personalized Disease Prediction, Prevention and Care (LUCAMP), the European Union (EUGENE2) grant LSHM-CT-2004-512013, EXGENESIS grant LSHM-CT-2004-005272, the Danish Diabetes Association and the Danish Agency for Science, Technology and Innovation, grant no. 271-06-0539. This study was supported in part by a grant from the European Union (Integrated Project EuroDia LSHM-CT-2006-518153 in the Framework Programme 6 [FP6] of the European Community). M.P. is the recipient of a Canadian Chair in diabetes and metabolism. R.S. is a Chercheur-boursier of the Fonds de la recherche en santé du Québec and the recipient of an MGH One Hundred and Seventy-Fifth Anniversary Award from Research Institute of the Montreal General Hospital Foundation. We thank L. Peltonen-Palotie for her contribution in DNA extraction and distribution; M. Deweider and F. Allegaert for the DNA bank management; R. Frechette, V. Catudal, D. Vincent, A. Forman, I.-L. Wantzin, T. Lorentzen, M. Stendal, M.H. Kristensen, T. Brunt and A.L. Nielsen for their technical or management assistance. Large-scale computations were performed using the Consortium Laval, Université du Québec, McGill and Eastern Quebec supercomputer facility. We are sincerely indebted to all subjects who participated in this study.

Author information

Author notes

  1. Johan Rung, Lishuang Shen, Ghislain Rocheleau & David Serre

    Present address: Current addresses: EMBL–European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK (J.R.); The Hospital for Sick Children Research Institute, Toronto, Canada (L.S.); Prognomix Inc., Montreal, Canada (G.R.); Genomic Medicine Institute, Lerner Research Institute, Cleveland, Ohio, USA (D.S.).,

  2. Johan Rung, Stéphane Cauchi and Anders Albrechtsen: These authors contributed equally to this work.

Authors and Affiliations

  1. McGill University and Génome Québec Innovation Centre, Montréal, Canada

    Johan Rung, Lishuang Shen, Ghislain Rocheleau, François Bacot, Alexandre Belisle, Alexander Mazur, Alexandre Montpetit, David Serre & Robert Sladek

  2. Centre National de la Recherche Scientifique–Unité Mixte de Recherche–8090, Institute of Biology and Lille 2 University, Pasteur Institute, Lille, France

    Stéphane Cauchi, Christine Cavalcanti-Proença, Christian Dina, Emmanuelle Durand, David Meyre, Martine Vaxillaire & Philippe Froguel

  3. Department of Biostatistics, University of Copenhagen, Copenhagen, Denmark

    Anders Albrechtsen

  4. Department of Human Genetics, Faculty of Medicine, McGill University, Montreal, Canada

    Ghislain Rocheleau, Constantin Polychronakos & Robert Sladek

  5. Institut National de la Santé et de la Recherche Médicale (INSERM), U780, Villejuif, France; and University Paris-Sud, Orsay, France

    Beverley Balkau

  6. Steno Diabetes Center, Gentofte, Denmark

    Knut Borch-Johnsen, Pernille Poulsen, Rasmus Ribel-Madsen & Allan Vaag

  7. Endocrinology-Diabetology Unit, Corbeil-Essonnes Hospital, Corbeil-Essonnes, France

    Guillaume Charpentier

  8. Department of Epidemiology and Public Health, Imperial College London, London, UK

    Paul Elliott, Marjo-Riitta Järvelin & Anneli Pouta

  9. Poitiers Hospital, Endocrinology and Diabetology, Centre d'Investigation Clinique INSERM 0801, INSERM U927, Université de Poitiers, Unité de Formation et de Recherche, Medecine Pharmacie, Poitiers, France

    Samy Hadjadj

  10. Institute of Health Sciences and Biocenter Oulu, University of Oulu, Oulu, Finland; and Department of Child and Adolescent Health, National Public Health Institute, Helsinki, Finland

    Marjo-Riitta Järvelin

  11. Finnish Institute of Occupational Health, Helsinki, Finland

    Jaana Laitinen

  12. Department of General Practice, University of Aarhus, Aarhus C, Denmark

    Torsten Lauritzen & Anelli Sandbaek

  13. Department of Endocrinology, Diabetology and Nutrition, Bichat-Claude Bernard University Hospital, Assistance Publique des Hôpitaux de Paris, Paris, France; INSERM U695, Université Paris 7, Paris, France; Diderot University, Paris, France

    Michel Marre

  14. Research Centre for Prevention and Health, Glostrup University Hospital, Glostrup, Denmark

    Charlotta Pisinger

  15. Department of Medicine, Faculty of Medicine, McGill University, Montreal, Canada

    Barry Posner & Robert Sladek

  16. Polypeptide Hormone Laboratory and Department of Anatomy and Cell Biology, McGill University, Montréal, Canada

    Barry Posner

  17. Public Health Science and General Practice, University of Oulu, Oulu, Finland

    Anneli Pouta

  18. Montreal Diabetes Research Center, Montreal, Canada; Molecular Nutrition Unit and the Department of Nutrition, University of Montréal and the Centre Hospitalier de l'Université de Montréal, Montréal, Canada

    Marc Prentki

  19. Department of Clinical Chemistry, University of Oulu, Oulu, Finland

    Aimo Ruokonen

  20. Institut Interrégional pour la Santé, La Riche, France

    Jean Tichet

  21. Copenhagen Muscle Research Centre, Institute of Exercise and Sport Sciences, University of Copenhagen, Copenhagen NV, Denmark

    Jørgen F P Wojtaszewski

  22. Department of Clinical Sciences, Unit of Diabetes and Endocrinology, Malmö University Hospital, Lund University, Malmö, Sweden

    Allan Vaag

  23. Hagedorn Research Institute and Steno Diabetes Center, Gentofte, Denmark

    Torben Hansen & Oluf Pedersen

  24. Faculty of Health Science, University of Southern Denmark, Odense M, Denmark

    Torben Hansen

  25. Department of Pediatrics, Faculty of Medicine, McGill University, Montreal, Canada

    Constantin Polychronakos

  26. Department of Biomedical Sciences, University of Copenhagen, Copenhagen N, Denmark; and Faculty of Health Sciences, University of Aarhus, Aarhus C, Denmark

    Oluf Pedersen

  27. Centre and Department of Genomic Medicine, Hammersmith Hospital, Imperial College London, London, UK

    Philippe Froguel

Authors
  1. Johan Rung
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Stéphane Cauchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Anders Albrechtsen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lishuang Shen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ghislain Rocheleau
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Christine Cavalcanti-Proença
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. François Bacot
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Beverley Balkau
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Alexandre Belisle
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Knut Borch-Johnsen
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Guillaume Charpentier
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Christian Dina
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Emmanuelle Durand
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Paul Elliott
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Samy Hadjadj
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Marjo-Riitta Järvelin
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Jaana Laitinen
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Torsten Lauritzen
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Michel Marre
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Alexander Mazur
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. David Meyre
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. Alexandre Montpetit
    View author publications

    You can also search for this author in PubMed Google Scholar

  23. Charlotta Pisinger
    View author publications

    You can also search for this author in PubMed Google Scholar

  24. Barry Posner
    View author publications

    You can also search for this author in PubMed Google Scholar

  25. Pernille Poulsen
    View author publications

    You can also search for this author in PubMed Google Scholar

  26. Anneli Pouta
    View author publications

    You can also search for this author in PubMed Google Scholar

  27. Marc Prentki
    View author publications

    You can also search for this author in PubMed Google Scholar

  28. Rasmus Ribel-Madsen
    View author publications

    You can also search for this author in PubMed Google Scholar

  29. Aimo Ruokonen
    View author publications

    You can also search for this author in PubMed Google Scholar

  30. Anelli Sandbaek
    View author publications

    You can also search for this author in PubMed Google Scholar

  31. David Serre
    View author publications

    You can also search for this author in PubMed Google Scholar

  32. Jean Tichet
    View author publications

    You can also search for this author in PubMed Google Scholar

  33. Martine Vaxillaire
    View author publications

    You can also search for this author in PubMed Google Scholar

  34. Jørgen F P Wojtaszewski
    View author publications

    You can also search for this author in PubMed Google Scholar

  35. Allan Vaag
    View author publications

    You can also search for this author in PubMed Google Scholar

  36. Torben Hansen
    View author publications

    You can also search for this author in PubMed Google Scholar

  37. Constantin Polychronakos
    View author publications

    You can also search for this author in PubMed Google Scholar

  38. Oluf Pedersen
    View author publications

    You can also search for this author in PubMed Google Scholar

  39. Philippe Froguel
    View author publications

    You can also search for this author in PubMed Google Scholar

  40. Robert Sladek
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

B.B., G.C., P.E., S.H., M.-R.J., J.L., M.M., O.P., T.H., T.L., K.B.-J., C. Pisinger, A.P., A.R., A.S. and J.T. recruited and phenotyped patient cohorts. F.B., A.B., E.D., A. Montpetit and L.S. designed and performed genotyping studies. P.P., R.R.-M., A.V. and J.F.P.W. performed hyperinsulinemic and euglycemic clamp studies as well as studies of muscle biopsies. A.A., S.C., C.C.-P., A. Mazur, G.R., J.R., D.S. and L.S. analyzed genotyping data. A.A., S.C., C.D., P.F., D.M., O.P., C. Polychronakos, B.P., M.P., J.R., R.S. and M.V. wrote the first draft of the manuscript. R.S., P.F. and O.P. planned and coordinated the study. All authors contributed to the final version of the manuscript.

Corresponding authors

Correspondence to Oluf Pedersen, Philippe Froguel or Robert Sladek.

Supplementary information

Supplementary Text and Figures

Supplementary Note, Supplementary Figures 1–4, Supplementary Tables 1–10. (PDF 1405 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rung, J., Cauchi, S., Albrechtsen, A. et al. Genetic variant near IRS1 is associated with type 2 diabetes, insulin resistance and hyperinsulinemia. Nat Genet 41, 1110–1115 (2009). https://doi.org/10.1038/ng.443

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ng.443

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing