Abstract

We report a genome-wide association study to iron status. We identify an association of SNPs in TPMRSS6 to serum iron (rs855791, combined P = 1.5 × 10−20), transferrin saturation (combined P = 2.2 × 10−23) and erythrocyte mean cell volume (MCV, combined P = 1.1 × 10−10). We also find suggestive evidence of association with blood hemoglobin levels (combined P = 5.3 × 10−7). These findings demonstrate the involvement of TMPRSS6 in control of iron homeostasis and in normal erythropoiesis.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1.

    et al. Am. J. Hum. Genet. 66, 1246–1258 (2000).

  2. 2.

    et al. Am. J. Hum. Genet. 84, 60–65 (2009).

  3. 3.

    et al. Nat. Genet. 40, 569–571 (2008).

  4. 4.

    et al. Eur. J. Hum. Genet. 16, 335–342 (2008).

  5. 5.

    et al. Haematologica 93, 1473–1479 (2008).

  6. 6.

    et al. Cell Metab. 8, 502–511 (2008).

  7. 7.

    , , , & Haematologica 94, 840–849 (2009).

  8. 8.

    Cell Metab. 8, 1–3 (2008).

  9. 9.

    et al. Cell Metab. 9, 217–227 (2009).

  10. 10.

    et al. PLoS Biol. 6, e107 (2008).

  11. 11.

    et al. Am. J. Hum. Genet. 81, 559–575 (2007).

  12. 12.

    et al. Nat. Genet. 40, 1056–1058 (2008).

Download references

Acknowledgements

We are grateful to the twins and their families for their generous participation in these studies. We would like to thank staff at the Queensland Institute of Medical Research: D. Statham, A. Eldridge and M. Grace for the Australian sample collection; L. Bowdler, S. Crooks and staff of the Molecular Epidemiology Laboratory for sample processing and preparation; D. Smyth and H. Beeby for IT support; M. Wright for supervision and A. McRae and S. Medland for discussion. For the Australian study, we acknowledge funding from the Australian National Health and Medical Research Council (NHMRC grants 241944, 389875, 389891, 389892, 389938, 442915, 442981, 496739 and 552485), US National Institutes of Health (NIH grants AA07535, AA10248 and AA014041) and the Australian Research Council (ARC grant DP0770096). For the Netherlands Twin Registry (NTR) and the Netherlands Study of Depression and Anxiety (NESDA) samples, we acknowledge support from The Netherlands Society for Scientific Research (NWO 904-61-090; 904-61-193; 480-04-004; 400-05-717; SPI 56-464-14192), Center for Medical Systems Biology (NWO Genomics); Geestkracht program of ZonMW (10-000-1002); matching funds from universities and mental health care institutes involved in NESDA (GGZ Buitenamstel-Geestgronden, Rivierduinen, University Medical Center Groningen, GGZ Lentis, GGZ Friesland, GGZ Drenthe); Centre for Neurogenomics and Cognitive Research VU University (CNCR-VU); European Science Foundation (EU/QLRT-2001-01254); NIMH (R01 MH059160); and matching funds from participating institutes in NTR and NESDA. Genotyping of NTR and NESDA samples was funded by the Genetic Association Information Network (GAIN) of the Foundation for the US National Institutes of Health, and analysis was supported by grants from GAIN and the National Institute of Mental Health (MH081802). B.B. is the recipient of an NHMRC Biomedical Postdoctoral Fellowship (552498). D.R.N., G.W.M and P.M.V. are supported by the NHMRC Fellowship Scheme.

Author information

Affiliations

  1. Queensland Institute of Medical Research, Brisbane, Queensland, Australia.

    • Beben Benyamin
    • , Manuel A R Ferreira
    • , Scott Gordon
    • , Rita P S Middelberg
    • , Brian P McEvoy
    • , Anjali K Henders
    • , Megan J Campbell
    • , Leanne Wallace
    • , Dale R Nyholt
    • , Peter M Visscher
    • , Nicholas G Martin
    • , Grant W Montgomery
    •  & John B Whitfield
  2. Netherlands Twin Register, Department of Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands.

    • Gonneke Willemsen
    • , Jouke-Jan Hottenga
    • , Eco J C de Geus
    •  & Dorret I Boomsma
  3. Centre for Immunology and Cancer Research, University of Queensland, Princess Alexandra Hospital, Brisbane, Queensland, Australia.

    • Ian H Frazer
  4. Department of Psychiatry, Washington University School of Medicine and Midwest Alcoholism Research Center, St. Louis, Missouri, USA.

    • Andrew C Heath
  5. Department of Psychiatry, VU University Medical Center, Amsterdam, The Netherlands.

    • Brenda W Penninx

Authors

  1. Search for Beben Benyamin in:

  2. Search for Manuel A R Ferreira in:

  3. Search for Gonneke Willemsen in:

  4. Search for Scott Gordon in:

  5. Search for Rita P S Middelberg in:

  6. Search for Brian P McEvoy in:

  7. Search for Jouke-Jan Hottenga in:

  8. Search for Anjali K Henders in:

  9. Search for Megan J Campbell in:

  10. Search for Leanne Wallace in:

  11. Search for Ian H Frazer in:

  12. Search for Andrew C Heath in:

  13. Search for Eco J C de Geus in:

  14. Search for Dale R Nyholt in:

  15. Search for Peter M Visscher in:

  16. Search for Brenda W Penninx in:

  17. Search for Dorret I Boomsma in:

  18. Search for Nicholas G Martin in:

  19. Search for Grant W Montgomery in:

  20. Search for John B Whitfield in:

Contributions

Study design and coordination: A.C.H., A.K.H., B.W.P., D.I.B., D.R.N., E.J.C.deG., G.W.M., I.H.F., J.B.W., N.G.M. and P.M.V. Obtaining study funding: A.C.H., B.W.P., D.I.B., D.R.N., E.J.C.deG., G.W.M., I.H.F., J.B.W., N.G.M. and P.M.V. Sample collection and phenotype data collection: A.C.H., A.K.H., D.R.N., G.W.M., I.H.F., J.B.W., L.W., M.J.C. and N.G.M. (Australian); B.W.P., D.I.B., E.J.C.deG., G.W. and J.-J.H. (Dutch). Data preparation: A.K.H., B.B., B.P.M., D.R.N., J.B.W., J.-J.H., L.W., M.J.C., R.P.S.M. and S.G. Statistical analyses: B.B., B.P.M., D.R.N., J.B.W., M.A.R.F., P.M.V. and S.G. Results interpretation: B.B., D.R.N., G.W.M., J.B.W., M.A.R.F., N.G.M. and P.M.V. Manuscript writing: B.B., M.A.R.F. and J.B.W. Review and revision of the manuscript: A.C.H., B.B., B.W.P., D.I.B., D.R.N., E.J.C.deG., G.W., G.W.M., J.B.W., M.A.R.F., N.G.M. and P.M.V. All authors contributed to the final version of the paper.

Corresponding author

Correspondence to Beben Benyamin.

Supplementary information

PDF files

  1. 1.

    Supplementary Text and Figures

    Supplementary Figures 1–4, Supplementary Tables 1–3 and Supplementary Methods

About this article

Publication history

Received

Accepted

Published

DOI

https://doi.org/10.1038/ng.456

Further reading