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Common variants in TMPRSS6 are associated with iron status and erythrocyte volume


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.

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Figure 1: Detailed results of the associations between SNPs within TMPRSS6 and transferrin saturation in the adolescent cohort.


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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  3. Finberg, K.E. et al. Nat. Genet. 40, 569–571 (2008).

    Article  CAS  Google Scholar 

  4. Boomsma, D.I. et al. Eur. J. Hum. Genet. 16, 335–342 (2008).

    Article  CAS  Google Scholar 

  5. Melis, M.A. et al. Haematologica 93, 1473–1479 (2008).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  7. Ramsay, A.J., Hooper, J.D., Folgueras, A.R., Velasco, G. & Lopez-Otin, C. Haematologica 94, 840–849 (2009).

    Article  CAS  Google Scholar 

  8. Muckenthaler, M.U. Cell Metab. 8, 1–3 (2008).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  10. Schadt, E.E. et al. PLoS Biol. 6, e107 (2008).

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

  12. Ferreira, M.A. et al. Nat. Genet. 40, 1056–1058 (2008).

    Article  CAS  Google Scholar 

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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.

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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.

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Correspondence to Beben Benyamin.

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Benyamin, B., Ferreira, M., Willemsen, G. et al. Common variants in TMPRSS6 are associated with iron status and erythrocyte volume. Nat Genet 41, 1173–1175 (2009).

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