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

Beben Benyamin*, Tonu Esko, Janina S Ried, Aparna Radhakrishnan, Sita H Vermeulen, Michela Traglia, Martin Gögele, Denise Anderson, Linda Broer, Clara Podmore, Jian'an Luan, Zoltan Kutalik, Serena Sanna, Peter van der Meer, Toshiko Tanaka, Fudi Wang, Harm-Jan Westra, Lude Franke, Evelin Mihailov, Lili MilaniJonas Hälldin, Jonas Häldin, Juliane Winkelmann, Thomas Meitinger, Joachim Thiery, Annette Peters, Melanie Waldenberger, Augusto Rendon, Jennifer Jolley, Jennifer Sambrook, Lambertus A Kiemeney, Fred C Sweep, Cinzia F Sala, Christine Schwienbacher, Irene Pichler, Jennie Hui, Ayse Demirkan, Aaron Isaacs, Najaf Amin, Maristella Steri, Gérard Waeber, Niek Verweij, Joseph E Powell, Dale R Nyholt, Andrew C Heath, Pamela A F Madden, Peter M Visscher, Margaret J Wright, Grant W Montgomery, Nicholas G Martin, InterAct Consortium, John B Whitfield*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

145 Citations (Web of Science)


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 languageEnglish
Pages (from-to)4926
JournalNature Communications
Publication statusPublished - 29 Oct 2014
Externally publishedYes


  • Adult
  • Chromosomes, Human, Pair 7/genetics
  • Ferritins/metabolism
  • Gene Expression Regulation
  • Genetic Association Studies
  • Genetic Loci
  • Genetic Predisposition to Disease
  • Hemochromatosis/blood
  • Homeostasis/genetics
  • Humans
  • Iron/blood
  • Lipids/blood
  • Phenotype
  • Polymorphism, Single Nucleotide/genetics
  • Reproducibility of Results
  • Risk Factors
  • Transferrin/metabolism
  • Correction: Corrigendum: Novel loci affecting iron homeostasis and their effects in individuals at risk for hemochromatosis

    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., Milani, L., & 49 othersHälldin, J., Winkelmann, J., Meitinger, T., Thiery, J., Peters, A., Waldenberger, M., Rendon, A., Jolley, J., Sambrook, J., Kiemeney, L. A., Sweep, F. C., Sala, C. F., Schwienbacher, C., Pichler, I., Hui, J., Demirkan, A., Isaacs, A., Amin, N., Steri, M., Waeber, G., Verweij, N., Powell, J. E., Nyholt, D. R., Heath, A. C., Madden, P. A. F., Visscher, P. M., Wright, M. J., Montgomery, G. W., Martin, N. G., Hernandez, D., Bandinelli, S., van der Harst, P., Uda, M., Vollenweider, P., Scott, R. A., Langenberg, C., Wareham, N. J., van Duijn, C., Beilby, J., Pramstaller, P. P., Hicks, A. A., Ouwehand, W. H., Oexle, K., Gieger, C., Metspalu, A., Camaschella, C., Toniolo, D., Swinkels, D. W. & Whitfield, J. B., 30 Mar 2015, In: Nature Communications. 6, p. 6542

    Research output: Contribution to journalErratum / corrigendum / retractionsAcademic

    Open Access
    2 Citations (Web of Science)

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