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Genome-wide association study identifies variants in TMPRSS6 associated with hemoglobin levels

Nature Genetics volume 41, pages 1170–1172 (2009)Cite this article

Abstract

We carried out a genome-wide association study of hemoglobin levels in 16,001 individuals of European and Indian Asian ancestry. The most closely associated SNP (rs855791) results in nonsynonymous (V736A) change in the serine protease domain of TMPRSS6 and a blood hemoglobin concentration 0.13 (95% CI 0.09–0.17) g/dl lower per copy of allele A (P = 1.6 × 10−13). Our findings suggest that TMPRSS6, a regulator of hepcidin synthesis and iron handling, is crucial in hemoglobin level maintenance.

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Acknowledgements

We thank the participants and research teams involved in LOLIPOP and NFBC1966, including P. Rantakallio, O. Tornwall and M. Jussila. The LOLIPOP study was supported by the British Heart Foundation (SP/04/002) and the Wellcome Trust. NFBC1966 was supported by the Academy of Finland (project grants 104781, 120315 and Center of Excellence in Complex Disease Genetics), University Hospital Oulu, Biocenter, University of Oulu, Finland, National Heart, Lung, and Blood Institute (US) grant 5R01HL087679-02 through the STAMPEED program (1RL1MH083268-01), ENGAGE project and grant agreement HEALTH-F4-2007-201413, the Medical Research Council (UK) (studentship grant G0500539, centre grant G0600705), the Wellcome Trust (UK) (project grant GR069224) and the Research Council UK fellowship. We thank the National Public Health Institute, Biomedicum Helsinki, Finland, supported financially by the Academy of Finland and Biocentrum Helsinki, for DNA extraction, sample quality controls, biobank upkeep and aliquotting.

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Author notes

  1. John C Chambers, Weihua Zhang, James Scott, Paul Elliott and Jaspal S Kooner: These authors contributed equally to this work.

Authors and Affiliations

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

    John C Chambers, Weihua Zhang, Delilah Zabaneh, Clive Hoggart, Marjo-Riitta Jarvelin & Paul Elliott

  2. Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, USA

    Yun Li & Gonçalo Abecasis

  3. National Heart and Lung Institute, London, UK

    Joban Sehmi, James Scott & Jaspal S Kooner

  4. Structural Bioinformatics Group, Imperial College London, London, UK

    Mark N Wass & Michael J E Sternberg

  5. Department of Structural & Molecular Biology, University College London, London, UK

    Henry Bayele & Surjit K Srai

  6. Oxford Centre for Diabetes, Endocrinology and Metabolism and Oxford NIHR Biomedical Research Centre, Oxford, UK

    Mark I McCarthy

  7. Wellcome Trust Sanger Institute, Cambridge, UK

    Leena Peltonen

  8. Center for Neurobehavioral Genetics, University of California, Los Angeles, California, USA

    Nelson B Freimer

  9. Division of Medicine, University College of London, London, UK

    Patrick H Maxwell

  10. Department of Clinical Chemistry, University Hospital Oulu, Oulu, Finland

    Aimo Ruokonen

  11. Institute of Health Sciences, Oulu, Finland

    Marjo-Riitta Jarvelin

  12. Biocenter Oulu, University of Oulu, Oulu, Finland

    Marjo-Riitta Jarvelin

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  1. John C Chambers
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Contributions

J.C.C., P.E., G.A., J. Scott and J.K. designed the study. J.C.C., J. Sehmi, M.-R.J., A.R. and J.K. supervised patient recruitment. J.C.C., P.E., J. Scott, G.A., M.I.M., H.B., L.P., N.B.F., M.J.E.S., P.H.M., S.K.S., M.-R.J., A.R. and J.K. supervised the experiments. J.C.C., W.Z., D.Z., Y.L., C.H. and M.N.W. performed data analysis. J.C.C., P.E., J. Scott and J.S.K. wrote the manuscript. All authors commented on and approved the manuscript.

Corresponding authors

Correspondence to John C Chambers or Jaspal S Kooner.

Supplementary information

Supplementary Text and Figures

Supplementary Methods, Supplementary Tables 1–4 and Supplementary Figures 1–3 (PDF 457 kb)

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Chambers, J., Zhang, W., Li, Y. et al. Genome-wide association study identifies variants in TMPRSS6 associated with hemoglobin levels. Nat Genet 41, 1170–1172 (2009). https://doi.org/10.1038/ng.462

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