Novel loci affecting iron homeostasis and their effects in individuals at risk for hemochromatosis

B. Benyamin; T. Esko; J.S. Ried; A. Radhakrishnan; S.H. Vermeulen; M. Traglia; M. Gögele; Denise Anderson; L. Broer; C. Podmore; J. Luan; Z. Kutalik; S. Sanna; P. Van Der Meer; T. Tanaka; F. Wang; H.-J. Westra; L. Franke; E. Mihailov; L. Milani; J. Häldin; J. Winkelmann; T. Meitinger; J. Thiery; A. Peters; M. Waldenberger; A. Rendon; J. Jolley; J. Sambrook; L.A. Kiemeney; F.C. Sweep; C.F. Sala; C. Schwienbacher; I. Pichler; Jennie Hui; A. Demirkan; A. Isaacs; N. Amin; M. Steri; G. Waeber; N. Verweij; J.E. Powell; D.R. Nyholt; A.C. Heath; P.A.F. Madden; P.M. Visscher; M.J. Wright; G.W. Montgomery; N.G. Martin; D. Hernandez; S. Bandinelli; P. Van Der Harst; M. Uda; P. Vollenweider; R.A. Scott; C. Langenberg; N.J. Wareham; C. Van Duijn; John Beilby; P.P. Pramstaller; A.A. Hicks; W.H. Ouwehand; K. Oexle; C. Gieger; A. Metspalu; C. Camaschella; D. Toniolo; D.W. Swinkels; J.B. Whitfield

doi:10.1038/ncomms5926

Novel loci affecting iron homeostasis and their effects in individuals at risk for hemochromatosis

B. Benyamin, T. Esko, J.S. Ried, A. Radhakrishnan, S.H. Vermeulen, M. Traglia, M. Gögele, Denise Anderson, L. Broer, C. Podmore, J. Luan, Z. Kutalik, S. Sanna, P. Van Der Meer, T. Tanaka, F. Wang, H.-J. Westra, L. Franke, E. Mihailov, L. MilaniJ. Häldin, J. Winkelmann, T. Meitinger, J. Thiery, A. Peters, M. Waldenberger, A. Rendon, J. Jolley, J. Sambrook, L.A. Kiemeney, F.C. Sweep, C.F. Sala, C. Schwienbacher, I. Pichler, Jennie Hui, A. Demirkan, A. Isaacs, N. Amin, M. Steri, G. Waeber, N. Verweij, J.E. Powell, D.R. Nyholt, A.C. Heath, P.A.F. Madden, P.M. Visscher, M.J. Wright, G.W. Montgomery, N.G. Martin, D. Hernandez, S. Bandinelli, P. Van Der Harst, M. Uda, P. Vollenweider, R.A. Scott, C. Langenberg, N.J. Wareham, C. Van Duijn, John Beilby, P.P. Pramstaller, A.A. Hicks, W.H. Ouwehand, K. Oexle, C. Gieger, A. Metspalu, C. Camaschella, D. Toniolo, D.W. Swinkels, J.B. Whitfield

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Abstract

Variation in body iron is associated with or causes diseases, including anaemia and iron overload. Here, we analyse genetic association data on biochemical markers of iron status from 11 European-population studies, with replication in eight additional cohorts (total up to 48,972 subjects). We find 11 genome-wide-significant (P<5 × 10⁻⁸) loci, some including known iron-related genes (HFE, SLC40A1, TF, TFR2, TFRC, TMPRSS6) and others novel (ABO, ARNTL, FADS2, NAT2, TEX14). SNPs at ARNTL, TF, and TFR2 affect iron markers in HFE C282Y homozygotes at risk for hemochromatosis. There is substantial overlap between our iron loci and loci affecting erythrocyte and lipid phenotypes. These results will facilitate investigation of the roles of iron in disease.

Original language	English
Pages (from-to)	1-10
Journal	Nature Communications
Volume	5
DOIs	https://doi.org/10.1038/ncomms5926
Publication status	Published - 29 Oct 2014

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10.1038/ncomms5926

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4215164/

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Benyamin, B., Esko, T., Ried, J. S., Radhakrishnan, A., Vermeulen, S. H., Traglia, M., Gögele, M., Anderson, D., Broer, L., Podmore, C., Luan, J., Kutalik, Z., Sanna, S., Van Der Meer, P., Tanaka, T., Wang, F., Westra, H.-J., Franke, L., Mihailov, E., ... Whitfield, J. B. (2014). Novel loci affecting iron homeostasis and their effects in individuals at risk for hemochromatosis. Nature Communications, 5, 1-10. https://doi.org/10.1038/ncomms5926

@article{c2a66538cd3047eb89173502cefc4f2a,

title = "Novel loci affecting iron homeostasis and their effects in individuals at risk for hemochromatosis",

abstract = "Variation in body iron is associated with or causes diseases, including anaemia and iron overload. Here, we analyse genetic association data on biochemical markers of iron status from 11 European-population studies, with replication in eight additional cohorts (total up to 48,972 subjects). We find 11 genome-wide-significant (P<5 × 10−8) loci, some including known iron-related genes (HFE, SLC40A1, TF, TFR2, TFRC, TMPRSS6) and others novel (ABO, ARNTL, FADS2, NAT2, TEX14). SNPs at ARNTL, TF, and TFR2 affect iron markers in HFE C282Y homozygotes at risk for hemochromatosis. There is substantial overlap between our iron loci and loci affecting erythrocyte and lipid phenotypes. These results will facilitate investigation of the roles of iron in disease. ",

author = "B. Benyamin and T. Esko and J.S. Ried and A. Radhakrishnan and S.H. Vermeulen and M. Traglia and M. G{\"o}gele and Denise Anderson and L. Broer and C. Podmore and J. Luan and Z. Kutalik and S. Sanna and {Van Der Meer}, P. and T. Tanaka and F. Wang and H.-J. Westra and L. Franke and E. Mihailov and L. Milani and J. H{\"a}ldin and J. Winkelmann and T. Meitinger and J. Thiery and A. Peters and M. Waldenberger and A. Rendon and J. Jolley and J. Sambrook and L.A. Kiemeney and F.C. Sweep and C.F. Sala and C. Schwienbacher and I. Pichler and Jennie Hui and A. Demirkan and A. Isaacs and N. Amin and M. Steri and G. Waeber and N. Verweij and J.E. Powell and D.R. Nyholt and A.C. Heath and P.A.F. Madden and P.M. Visscher and M.J. Wright and G.W. Montgomery and N.G. Martin and D. Hernandez and S. Bandinelli and {Van Der Harst}, P. and M. Uda and P. Vollenweider and R.A. Scott and C. Langenberg and N.J. Wareham and {Van Duijn}, C. and John Beilby and P.P. Pramstaller and A.A. Hicks and W.H. Ouwehand and K. Oexle and C. Gieger and A. Metspalu and C. Camaschella and D. Toniolo and D.W. Swinkels and J.B. Whitfield",

year = "2014",

month = oct,

day = "29",

doi = "10.1038/ncomms5926",

language = "English",

volume = "5",

pages = "1--10",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group - Macmillan Publishers",

}

Benyamin, B, Esko, T, Ried, JS, Radhakrishnan, A, Vermeulen, SH, Traglia, M, Gögele, M, Anderson, D, Broer, L, Podmore, C, Luan, J, Kutalik, Z, Sanna, S, Van Der Meer, P, Tanaka, T, Wang, F, Westra, H-J, Franke, L, Mihailov, E, Milani, L, Häldin, J, Winkelmann, J, Meitinger, T, Thiery, J, Peters, A, Waldenberger, M, Rendon, A, Jolley, J, Sambrook, J, Kiemeney, LA, Sweep, FC, Sala, CF, Schwienbacher, C, Pichler, I, Hui, J, Demirkan, A, Isaacs, A, Amin, N, Steri, M, Waeber, G, Verweij, N, Powell, JE, Nyholt, DR, Heath, AC, Madden, PAF, Visscher, PM, Wright, MJ, Montgomery, GW, Martin, NG, Hernandez, D, Bandinelli, S, Van Der Harst, P, Uda, M, Vollenweider, P, Scott, RA, Langenberg, C, Wareham, NJ, Van Duijn, C, Beilby, J, Pramstaller, PP, Hicks, AA, Ouwehand, WH, Oexle, K, Gieger, C, Metspalu, A, Camaschella, C, Toniolo, D, Swinkels, DW & Whitfield, JB 2014, 'Novel loci affecting iron homeostasis and their effects in individuals at risk for hemochromatosis', Nature Communications, vol. 5, pp. 1-10. https://doi.org/10.1038/ncomms5926

TY - JOUR

T1 - Novel loci affecting iron homeostasis and their effects in individuals at risk for hemochromatosis

AU - Benyamin, B.

AU - Esko, T.

AU - Ried, J.S.

AU - Radhakrishnan, A.

AU - Vermeulen, S.H.

AU - Traglia, M.

AU - Gögele, M.

AU - Anderson, Denise

AU - Broer, L.

AU - Podmore, C.

AU - Luan, J.

AU - Kutalik, Z.

AU - Sanna, S.

AU - Van Der Meer, P.

AU - Tanaka, T.

AU - Wang, F.

AU - Westra, H.-J.

AU - Franke, L.

AU - Mihailov, E.

AU - Milani, L.

AU - Häldin, J.

AU - Winkelmann, J.

AU - Meitinger, T.

AU - Thiery, J.

AU - Peters, A.

AU - Waldenberger, M.

AU - Rendon, A.

AU - Jolley, J.

AU - Sambrook, J.

AU - Kiemeney, L.A.

AU - Sweep, F.C.

AU - Sala, C.F.

AU - Schwienbacher, C.

AU - Pichler, I.

AU - Hui, Jennie

AU - Demirkan, A.

AU - Isaacs, A.

AU - Amin, N.

AU - Steri, M.

AU - Waeber, G.

AU - Verweij, N.

AU - Powell, J.E.

AU - Nyholt, D.R.

AU - Heath, A.C.

AU - Madden, P.A.F.

AU - Visscher, P.M.

AU - Wright, M.J.

AU - Montgomery, G.W.

AU - Martin, N.G.

AU - Hernandez, D.

AU - Bandinelli, S.

AU - Van Der Harst, P.

AU - Uda, M.

AU - Vollenweider, P.

AU - Scott, R.A.

AU - Langenberg, C.

AU - Wareham, N.J.

AU - Van Duijn, C.

AU - Beilby, John

AU - Pramstaller, P.P.

AU - Hicks, A.A.

AU - Ouwehand, W.H.

AU - Oexle, K.

AU - Gieger, C.

AU - Metspalu, A.

AU - Camaschella, C.

AU - Toniolo, D.

AU - Swinkels, D.W.

AU - Whitfield, J.B.

PY - 2014/10/29

Y1 - 2014/10/29

N2 - Variation in body iron is associated with or causes diseases, including anaemia and iron overload. Here, we analyse genetic association data on biochemical markers of iron status from 11 European-population studies, with replication in eight additional cohorts (total up to 48,972 subjects). We find 11 genome-wide-significant (P<5 × 10−8) loci, some including known iron-related genes (HFE, SLC40A1, TF, TFR2, TFRC, TMPRSS6) and others novel (ABO, ARNTL, FADS2, NAT2, TEX14). SNPs at ARNTL, TF, and TFR2 affect iron markers in HFE C282Y homozygotes at risk for hemochromatosis. There is substantial overlap between our iron loci and loci affecting erythrocyte and lipid phenotypes. These results will facilitate investigation of the roles of iron in disease.

AB - Variation in body iron is associated with or causes diseases, including anaemia and iron overload. Here, we analyse genetic association data on biochemical markers of iron status from 11 European-population studies, with replication in eight additional cohorts (total up to 48,972 subjects). We find 11 genome-wide-significant (P<5 × 10−8) loci, some including known iron-related genes (HFE, SLC40A1, TF, TFR2, TFRC, TMPRSS6) and others novel (ABO, ARNTL, FADS2, NAT2, TEX14). SNPs at ARNTL, TF, and TFR2 affect iron markers in HFE C282Y homozygotes at risk for hemochromatosis. There is substantial overlap between our iron loci and loci affecting erythrocyte and lipid phenotypes. These results will facilitate investigation of the roles of iron in disease.

U2 - 10.1038/ncomms5926

DO - 10.1038/ncomms5926

M3 - Article

SN - 2041-1723

VL - 5

SP - 1

EP - 10

JO - Nature Communications

JF - Nature Communications

ER -

Novel loci affecting iron homeostasis and their effects in individuals at risk for hemochromatosis

Abstract

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