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

Benyamin, Beben, Esko, Tonu, Ried, Janina S., Radhakrishnan, Aparna, Vermeulen, Sita H., Traglia, Michela, Goegele, Martin, Anderson, Denise, Broer, Linda, Podmore, Clara, Luan, Jian'an, Kutalik, Zoltan, Sanna, Serena, van der Meer, Peter, Tanaka, Toshiko, Wang, Fudi, Westra, Harm-Jan, Franke, Lude, Mihailov, Evelin, Milani, Lili, Haeldin, Jonas, Winkelmann, Juliane, Meitinger, Thomas, Thiery, Joachim, Peters, Annette, Waldenberger, Melanie, Rendon, Augusto, Jolley, Jennifer, Sambrook, Jennifer, Kiemeney, Lambertus A., Sweep, Fred C., Sala, Cinzia F., Schwienbacher, Christine, Pichler, Irene, Hui, Jennie, Demirkan, Ayse, Isaacs, Aaron, Amin, Najaf, Steri, Maristella, Waeber, Gerard, Verweij, Niek, Powell, Joseph E., Nyholt, Dale R., Heath, Andrew C., Madden, Pamela A. F., Visscher, Peter M., Wright, Margaret J., Montgomery, Grant W., Martin, Nicholas G., Hernandez, Dena, Bandinelli, Stefania, van der Harst, Pim, Uda, Manuela, Vollenweider, Peter, Scott, Robert A., Langenberg, Claudia, Wareham, Nicholas J., van Duijn, Cornelia, Beilby, John, Pramstaller, Peter P., Hicks, Andrew A., Ouwehand, Willem H., Oexle, Konrad, Gieger, Christian, Metspalu, Andres, Camaschella, Clara, Toniolo, Daniela, Swinkels, Dorine W. and Whitfield, John B. (2014) Novel loci affecting iron homeostasis and their effects in individuals at risk for hemochromatosis. Nature Communications, 5 4926.1-4926.10. doi:10.1038/ncomms5926

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Author Benyamin, Beben
Esko, Tonu
Ried, Janina S.
Radhakrishnan, Aparna
Vermeulen, Sita H.
Traglia, Michela
Goegele, Martin
Anderson, Denise
Broer, Linda
Podmore, Clara
Luan, Jian'an
Kutalik, Zoltan
Sanna, Serena
van der Meer, Peter
Tanaka, Toshiko
Wang, Fudi
Westra, Harm-Jan
Franke, Lude
Mihailov, Evelin
Milani, Lili
Haeldin, Jonas
Winkelmann, Juliane
Meitinger, Thomas
Thiery, Joachim
Peters, Annette
Waldenberger, Melanie
Rendon, Augusto
Jolley, Jennifer
Sambrook, Jennifer
Kiemeney, Lambertus A.
Sweep, Fred C.
Sala, Cinzia F.
Schwienbacher, Christine
Pichler, Irene
Hui, Jennie
Demirkan, Ayse
Isaacs, Aaron
Amin, Najaf
Steri, Maristella
Waeber, Gerard
Verweij, Niek
Powell, Joseph E.
Nyholt, Dale R.
Heath, Andrew C.
Madden, Pamela A. F.
Visscher, Peter M.
Wright, Margaret J.
Montgomery, Grant W.
Martin, Nicholas G.
Hernandez, Dena
Bandinelli, Stefania
van der Harst, Pim
Uda, Manuela
Vollenweider, Peter
Scott, Robert A.
Langenberg, Claudia
Wareham, Nicholas J.
van Duijn, Cornelia
Beilby, John
Pramstaller, Peter P.
Hicks, Andrew A.
Ouwehand, Willem H.
Oexle, Konrad
Gieger, Christian
Metspalu, Andres
Camaschella, Clara
Toniolo, Daniela
Swinkels, Dorine W.
Whitfield, John B.
Title Novel loci affecting iron homeostasis and their effects in individuals at risk for hemochromatosis
Journal name Nature Communications   Check publisher's open access policy
ISSN 2041-1723
Publication date 2014-10-29
Year available 2014
Sub-type Article (original research)
DOI 10.1038/ncomms5926
Open Access Status File (Publisher version)
Volume 5
Start page 4926.1
End page 4926.10
Total pages 10
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Subject 1600 Chemistry
1300 Biochemistry, Genetics and Molecular Biology
3100 Physics and Astronomy
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.
Formatted 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.
Keyword Genome-wide association
Transferrin receptor 2
Hfe hereditary hemochromatosis
Coronary artery disease
Foam cell formation
Circadian rhythm
Genetic variants
Common variants
Total mortality
Ferritin levels
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID RP-PG-0310-1002
R01 AA014041
MC_UU_12015/1
MC_U106179471
U54 EB020403
RG/09/012/28096
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
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