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.
authors.affiliation: 1] The University of Queensland, Queensland Brain Institute, Brisbane, Queensland 4072, Australia [2] QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4029, Australia.
authors.forename: Beben
authors.initials: B
authors.lastname: Benyamin
authors.affiliation: 1] Estonian Genome Center, University of Tartu, Riia 23b, 51010 Tartu, Estonia [2] The Broad Institute of Massachusetts Institute of Technology and Harvard University, 320 Charles St, Cambridge, Massachusetts 02141, USA.
authors.forename: Tonu
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authors.lastname: Esko
authors.affiliation: Institute of Genetic Epidemiology, Helmholtz Zentrum München, Ingolstädter Landstraße 1, 85764 Neuherberg, Germany.
authors.forename: Janina S
authors.initials: JS
authors.lastname: Ried
authors.affiliation: Department of Haematology, University of Cambridge, Cambridge Biomedical Campus Box 139, Hills Road, Cambridge CB2 0XY, UK.
authors.forename: Aparna
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authors.lastname: Radhakrishnan
authors.affiliation: 1] Department for Health Evidence, Radboud University Medical Centre, Geert Grooteplein-Zuid 10, 6525GA Nijmegen, The Netherlands [2] Department of Genetics, Radboud University Medical Centre, Geert Grooteplein-Zuid 10, 6525 GA, Nijmegen, The Netherlands.
authors.forename: Sita H
authors.initials: SH
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authors.forename: Michela
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authors.lastname: Traglia
authors.affiliation: Center for Biomedicine, European Academy of Bolzano/Bozen (EURAC), Via Galvani 31, 39100 Bolzano, Italy.
authors.forename: Martin
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authors.lastname: Gögele
authors.affiliation: Telethon Institute for Child Health Research, Centre for Child Health Research, The University of Western Australia, PO Box 855, West Perth, Western Australia 6872, Australia.
authors.forename: Denise
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authors.lastname: Anderson
authors.affiliation: 1] Department of Epidemiology, Subdivision Genetic Epidemiology, Erasmus Medical Center, Postbus 2040, 3000 CA Rotterdam, The Netherlands [2] Department of Internal Medicine, Erasmus Medical Center, Postbus 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: Linda
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authors.lastname: Broer
authors.affiliation: MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK.
authors.forename: Clara
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authors.lastname: Podmore
authors.affiliation: MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK.
authors.forename: Jian'an
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authors.lastname: Luan
authors.affiliation: 1] Institute of Social and Preventive Medicine (IUMSP), Centre Hospitalier Universitaire Vaudois (CHUV), Rte de la Corniche 10, 1010 Lausanne, Switzerland [2] Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland.
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Kutalik
authors.affiliation: Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche (CNR), Monserrato, 09042 Cagliari, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Sanna
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Cardiology, 9700 RB Groningen, The Netherlands.
authors.forename: Peter
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authors.lastname: van der Meer
authors.affiliation: Translational Gerontology Branch, National Institute on Aging, 251 Bayview Boulevard, Suite 100, Baltimore, Maryland 21224-6825, USA.
authors.forename: Toshiko
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authors.lastname: Tanaka
authors.affiliation: School of Public Health, Zhejiang University, Hangzhou 310058, P. R. China.
authors.forename: Fudi
authors.initials: F
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authors.affiliation: Department of Genetics, University Medical Center Groningen, P.O. Box 30001, 9700 RB Groningen, The Netherlands.
authors.forename: Harm-Jan
authors.initials: HJ
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authors.affiliation: Department of Genetics, University Medical Center Groningen, P.O. Box 30001, 9700 RB Groningen, The Netherlands.
authors.forename: Lude
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authors.lastname: Franke
authors.affiliation: 1] Estonian Genome Center, University of Tartu, Riia 23b, 51010 Tartu, Estonia [2] Institute of Molecular and Cell Biology, University of Tartu, Tartu 51010, Estonia.
authors.forename: Evelin
authors.initials: E
authors.lastname: Mihailov
authors.affiliation: Estonian Genome Center, University of Tartu, Riia 23b, 51010 Tartu, Estonia.
authors.forename: Lili
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authors.affiliation: Estonian Genome Center, University of Tartu, Riia 23b, 51010 Tartu, Estonia.
authors.forename: Jonas
authors.initials: J
authors.lastname: Häldin
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authors.forename: Juliane
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authors.lastname: Winkelmann
authors.affiliation: 1] Institut für Humangenetik, Helmholtz Zentrum München, 85764 Neuherberg, Germany [2] Institute of Human Genetics, Klinikum Rechts der Isar, Technische Universität München, Ismaninger Straße 22, 81675 München, Germany.
authors.forename: Thomas
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authors.affiliation: 1] Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, Universitätsklinikum Leipzig, Liebigstraße 27, 04103 Leipzig, Germany [2] LIFE Research Center for Civilization Diseases, Medical Faculty, University Leipzig, Philipp-Rosenthal-Straße 27, 04103 Leipzig, Germany.
authors.forename: Joachim
authors.initials: J
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authors.affiliation: 1] Institute of Epidemiology II, Helmholtz Zentrum München - German Research Center for Environmental Health, Ingolstädter Landstraße 1, 85764 Neuherberg, Germany [2] Research Unit of Molecular Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Ingolstädter Landstraße 1, 85764 Neuherberg, Germany.
authors.forename: Annette
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authors.lastname: Peters
authors.affiliation: 1] Institute of Epidemiology II, Helmholtz Zentrum München - German Research Center for Environmental Health, Ingolstädter Landstraße 1, 85764 Neuherberg, Germany [2] Research Unit of Molecular Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Ingolstädter Landstraße 1, 85764 Neuherberg, Germany.
authors.forename: Melanie
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authors.lastname: Waldenberger
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authors.forename: Augusto
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authors.forename: Lambertus A
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authors.affiliation: Laboratory of Genetic, Endocrine and Metabolic Diseases (LGEM), Department of Laboratory Medicine, Radboud University Medical Centre, Geert Grooteplein-Zuid 10, 6525 GA Nijmegen, The Netherlands.
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authors.initials: FC
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authors.initials: CF
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authors.forename: Ayse
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authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4029, Australia.
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authors.affiliation: Department of Psychiatry, Washington University, 660S Euclid Avenue, St. Louis, Missouri 63110, USA.
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authors.affiliation: Department of Psychiatry, Washington University, 660S Euclid Avenue, St. Louis, Missouri 63110, USA.
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authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4029, Australia.
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authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4029, Australia.
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authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4029, Australia.
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authors.affiliation: 1] University of Groningen, University Medical Center Groningen, Department of Cardiology, 9700 RB Groningen, The Netherlands [2] Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, 3511 GC Utrecht, The Netherlands [3] University of Groningen, University Medical Center Groningen, Department of Genetics, 9700 RB Groningen, The Netherlands.
authors.forename: Pim
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authors.affiliation: Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche (CNR), Monserrato, 09042 Cagliari, Italy.
authors.forename: Manuela
authors.initials: M
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authors.affiliation: Department of Medicine, Internal Medicine, CHUV, University of Lausanne, Rue du Bugnon 46, 1011 Lausanne, Switzerland.
authors.forename: Peter
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authors.lastname: Vollenweider
authors.affiliation: MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK.
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authors.initials: RA
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authors.affiliation: MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK.
authors.forename: Claudia
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authors.affiliation: MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK.
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authors.initials: NJ
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authors.forename: Cornelia
authors.initials: C
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authors.forename: John
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authors.forename: Peter P
authors.initials: PP
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authors.affiliation: Center for Biomedicine, European Academy of Bolzano/Bozen (EURAC), Via Galvani 31, 39100 Bolzano, Italy.
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Hicks
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authors.initials: WH
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authors.forename: Konrad
authors.initials: K
authors.lastname: Oexle
authors.affiliation: 1] Institute of Genetic Epidemiology, Helmholtz Zentrum München, Ingolstädter Landstraße 1, 85764 Neuherberg, Germany [2] Institute of Epidemiology II, Helmholtz Zentrum München - German Research Center for Environmental Health, Ingolstädter Landstraße 1, 85764 Neuherberg, Germany [3] Research Unit of Molecular Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Ingolstädter Landstraße 1, 85764 Neuherberg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Gieger
authors.affiliation: Estonian Genome Center, University of Tartu, Riia 23b, 51010 Tartu, Estonia.
authors.forename: Andres
authors.initials: A
authors.lastname: Metspalu
authors.affiliation: 1] Division of Genetics and Cell Biology, San Raffaele Scientific Institute, 20132 Milano, Italy [2] Vita-Salute University, 20132 Milan, Italy.
authors.forename: Clara
authors.initials: C
authors.lastname: Camaschella
authors.affiliation: Division of Genetics and Cell Biology, San Raffaele Scientific Institute, 20132 Milano, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Toniolo
authors.affiliation: Laboratory of Genetic, Endocrine and Metabolic Diseases (LGEM), Department of Laboratory Medicine, Radboud University Medical Centre, Geert Grooteplein-Zuid 10, 6525 GA Nijmegen, The Netherlands.
authors.forename: Dorine W
authors.initials: DW
authors.lastname: Swinkels
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4029, Australia.
authors.forename: John B
authors.initials: JB
authors.lastname: Whitfield
mesh_terms: D000328:Adult; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D005293:Ferritins / Q000378:metabolism; D005786:Gene Expression Regulation; D056726:Genetic Association Studies; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D006432:Hemochromatosis / Q000097:blood / Q000235:genetics*; D006706:Homeostasis / Q000235:genetics*; D006801:Humans; D007501:Iron / Q000097:blood / Q000378:metabolism*; D008055:Lipids / Q000097:blood; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015203:Reproducibility of Results; D012307:Risk Factors; D014168:Transferrin / Q000378:metabolism
chemical_list: D008055:Lipids; D014168:Transferrin; D005293:Ferritins; D007501:Iron