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

2014; Nature Portfolio; Volume: 5; Issue: 1 Linguagem: Inglês

10.1038/ncomms5926

2041-1723

Beben Benyamin, Tõnu Esko, Janina S. Ried, Aparna Radhakrishnan, Sita H. Vermeulen, Michela Traglia, Martin Gögele, Denise Anderson, Linda Broer, Clara Podmore, Jian’an Luan, Zoltán Kutalik, Serena Sanna, Peter van der Meer, Toshiko Tanaka, Fudi Wang, Harm-Jan Westra, Lude Franke, Evelin Mihailov, Lili Milani, Jonas Hälldin, Juliane Winkelmann, Thomas Meitinger, Joachim Thiery, Annette Peters, Mélanie Waldenberger, Augusto Rendon, Jennifer Jolley, Jennifer Sambrook, Lambertus A. Kiemeney, Fred C.G.J. Sweep, Cinzia Sala, Christine Schwienbacher, Irene Pichler, Jennie Hui, Ayşe 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, Dena Hernández, Stefania Bandinelli, Pim van der Harst, Manuela Uda, Péter Vollenweider, Robert A. Scott, Claudia Langenberg, Nicholas J. Wareham, Cornelia M. van Duijn, John Beilby, Peter P. Pramstaller, Andrew A. Hicks, Willem H. Ouwehand, Konrad Oexle, Christian Gieger, Andres Metspalu, Clara Camaschella, Daniela Toniolo, Dorine W. Swinkels, John B. Whitfield,

Folate and B Vitamins Research

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. Iron deficiency is the leading cause of anaemia and is known to compromise immune function. Here, the authors identify several new genes associated with iron status in European populations and provide insight into how iron levels may be linked to the risk of metabolic disease.