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


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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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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Authors and Affiliations



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.

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Correspondence to John C Chambers or Jaspal S Kooner.

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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).

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