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, Gögele, 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, Häldin, 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, Gérard, 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. (2014) Novel loci affecting iron homeostasis and their effects in individuals at risk for hemochromatosis. Nature Communications, 5, Article Number-4926.

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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.

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ID Code: 84357
Item Type: Journal Article
Refereed: Yes
Keywords: ABO protein, arylamine acetyltransferase, biochemical marker, C reactive protein, CD71 antigen, fatty acid desaturase 2, HFE protein, iron, lipoprotein, serine proteinase, solute carrier family 40, TEX14 protein, transcription factor ARNTL, transferrin, transferrin receptor, transferrin receptor 2, transmembrane protease serine 6, unclassified drug, anemia, biomarker, cohort analysis, disease incidence, gene expression, homeostasis, iron, phenotype, lipoprotein metabolism, major clinical study, meta analysis (topic), phenotypic variation, risk assessment, risk factor, single nucleotide polymorphism, transferrin blood level
DOI: 10.1038/ncomms5926
ISSN: 2041-1723
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2014 Macmillan Publishers Limited
Deposited On: 19 May 2015 23:28
Last Modified: 02 Feb 2016 02:04

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