Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
25352340
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.
DATE PUBLISHED
2014
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2014/05/01
accepted 2014/08/06
entrez 2014/10/30 06:00
pubmed 2014/10/30 06:00
medline 2015/10/21 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Benyamin B Benyamin Beben B 1] The University of Queensland, Queensland Brain Institute, Brisbane, Queensland 4072, Australia [2] QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4029, Australia.
Esko T Esko Tonu T 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.
Ried JS Ried Janina S JS Institute of Genetic Epidemiology, Helmholtz Zentrum München, Ingolstädter Landstraße 1, 85764 Neuherberg, Germany.
Radhakrishnan A Radhakrishnan Aparna A Department of Haematology, University of Cambridge, Cambridge Biomedical Campus Box 139, Hills Road, Cambridge CB2 0XY, UK.
Vermeulen SH Vermeulen Sita H SH 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.
Traglia M Traglia Michela M 1] Division of Genetics and Cell Biology, San Raffaele Scientific Institute, 20132 Milano, Italy [2] Institute for Maternal and Child Health-IRCCS ''Burlo Garofolo''- Trieste, 34137 Trieste, Italy.
Gögele M Gögele Martin M Center for Biomedicine, European Academy of Bolzano/Bozen (EURAC), Via Galvani 31, 39100 Bolzano, Italy.
Anderson D Anderson Denise D 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.
Broer L Broer Linda L 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.
Podmore C Podmore Clara C MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK.
Luan J Luan Jian'an J MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK.
Kutalik Z Kutalik Zoltan Z 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.
Sanna S Sanna Serena S Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche (CNR), Monserrato, 09042 Cagliari, Italy.
van der Meer P van der Meer Peter P University of Groningen, University Medical Center Groningen, Department of Cardiology, 9700 RB Groningen, The Netherlands.
Tanaka T Tanaka Toshiko T Translational Gerontology Branch, National Institute on Aging, 251 Bayview Boulevard, Suite 100, Baltimore, Maryland 21224-6825, USA.
Wang F Wang Fudi F School of Public Health, Zhejiang University, Hangzhou 310058, P. R. China.
Westra HJ Westra Harm-Jan HJ Department of Genetics, University Medical Center Groningen, P.O. Box 30001, 9700 RB Groningen, The Netherlands.
Franke L Franke Lude L Department of Genetics, University Medical Center Groningen, P.O. Box 30001, 9700 RB Groningen, The Netherlands.
Mihailov E Mihailov Evelin E 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.
Milani L Milani Lili L Estonian Genome Center, University of Tartu, Riia 23b, 51010 Tartu, Estonia.
Hälldin J Hälldin Jonas J Estonian Genome Center, University of Tartu, Riia 23b, 51010 Tartu, Estonia.
Häldin J Häldin Jonas J Estonian Genome Center, University of Tartu, Riia 23b, 51010 Tartu, Estonia.
Winkelmann J Winkelmann Juliane J 1] Department of Neurology and Neurosciences and Center for Sleep Sciences and Medicine, Stanford University, Palo Alto, California 94304, USA [2] Neurologische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany [3] Institut für Humangenetik, Helmholtz Zentrum München, 85764 Neuherberg, Germany [4] Munich Cluster for Systems Neurology (SyNergy), 81675 Munich, Germany.
Meitinger T Meitinger Thomas T 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.
Thiery J Thiery Joachim J 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.
Peters A Peters Annette A 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.
Waldenberger M Waldenberger Melanie M 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.
Rendon A Rendon Augusto A 1] Department of Haematology, University of Cambridge, Cambridge Biomedical Campus Box 139, Hills Road, Cambridge CB2 0XY, UK [2] NHS Blood and Transplant, Cambridge Biomedical Campus, Long Road, Cambridge CB2 0PT, UK [3] Medical Research Council Biostatistics Unit, Cambridge Biomedical Campus, Cambridge CB2 0SR, UK.
Jolley J Jolley Jennifer J 1] Department of Haematology, University of Cambridge, Cambridge Biomedical Campus Box 139, Hills Road, Cambridge CB2 0XY, UK [2] NHS Blood and Transplant, Cambridge Biomedical Campus, Long Road, Cambridge CB2 0PT, UK.
Sambrook J Sambrook Jennifer J 1] Department of Haematology, University of Cambridge, Cambridge Biomedical Campus Box 139, Hills Road, Cambridge CB2 0XY, UK [2] NHS Blood and Transplant, Cambridge Biomedical Campus, Long Road, Cambridge CB2 0PT, UK.
Kiemeney LA Kiemeney Lambertus A LA 1] Department for Health Evidence, Radboud University Medical Centre, Geert Grooteplein-Zuid 10, 6525GA Nijmegen, The Netherlands [2] Department of Urology, Radboud University Medical Centre, Geert Grooteplein-Zuid 10, 6525GA Nijmegen, The Netherlands.
Sweep FC Sweep Fred C FC 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.
Sala CF Sala Cinzia F CF Division of Genetics and Cell Biology, San Raffaele Scientific Institute, 20132 Milano, Italy.
Schwienbacher C Schwienbacher Christine C Center for Biomedicine, European Academy of Bolzano/Bozen (EURAC), Via Galvani 31, 39100 Bolzano, Italy.
Pichler I Pichler Irene I Center for Biomedicine, European Academy of Bolzano/Bozen (EURAC), Via Galvani 31, 39100 Bolzano, Italy.
Hui J Hui Jennie J 1] PathWest Laboratory Medicine of WA, Nedlands, Western Australia 6009, Australia [2] Schools of Pathology and Laboratory Medicine, and Population Health, The University of Western Australia, Nedlands, Western Australia 6009, Australia.
Demirkan A Demirkan Ayse A 1] Department of Epidemiology, Subdivision Genetic Epidemiology, Erasmus Medical Center, Postbus 2040, 3000 CA Rotterdam, The Netherlands [2] Department of Human Genetics, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands.
Isaacs A Isaacs Aaron A 1] Department of Epidemiology, Subdivision Genetic Epidemiology, Erasmus Medical Center, Postbus 2040, 3000 CA Rotterdam, The Netherlands [2] Center of Medical Systems Biology, Einthovenweg 20, 2333 ZC Leiden, The Netherlands.
Amin N Amin Najaf N Department of Epidemiology, Subdivision Genetic Epidemiology, Erasmus Medical Center, Postbus 2040, 3000 CA Rotterdam, The Netherlands.
Steri M Steri Maristella M Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche (CNR), Monserrato, 09042 Cagliari, Italy.
Waeber G Waeber Gérard G Department of Medicine, Internal Medicine, CHUV, University of Lausanne, Rue du Bugnon 46, 1011 Lausanne, Switzerland.
Verweij N Verweij Niek N University of Groningen, University Medical Center Groningen, Department of Cardiology, 9700 RB Groningen, The Netherlands.
Powell JE Powell Joseph E JE 1] The University of Queensland, Queensland Brain Institute, Brisbane, Queensland 4072, Australia [2] University of Queensland Diamantina Institute, University of Queensland, Princess Alexandra Hospital, Brisbane, Queensland 4072, Australia.
Nyholt DR Nyholt Dale R DR QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4029, Australia.
Heath AC Heath Andrew C AC Department of Psychiatry, Washington University, 660S Euclid Avenue, St. Louis, Missouri 63110, USA.
Madden PA Madden Pamela A F PA Department of Psychiatry, Washington University, 660S Euclid Avenue, St. Louis, Missouri 63110, USA.
Visscher PM Visscher Peter M PM 1] The University of Queensland, Queensland Brain Institute, Brisbane, Queensland 4072, Australia [2] University of Queensland Diamantina Institute, University of Queensland, Princess Alexandra Hospital, Brisbane, Queensland 4072, Australia.
Wright MJ Wright Margaret J MJ QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4029, Australia.
Montgomery GW Montgomery Grant W GW QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4029, Australia.
Martin NG Martin Nicholas G NG QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4029, Australia.
Hernandez D Hernandez Dena D Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland 20892, USA.
Bandinelli S Bandinelli Stefania S Geriatric Unit, Azienda Sanitaria Firenze (ASF), Via delle Casine, 16, 50122 Firenze, Italy.
van der Harst P van der Harst Pim P 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.
Uda M Uda Manuela M Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche (CNR), Monserrato, 09042 Cagliari, Italy.
Vollenweider P Vollenweider Peter P Department of Medicine, Internal Medicine, CHUV, University of Lausanne, Rue du Bugnon 46, 1011 Lausanne, Switzerland.
Scott RA Scott Robert A RA MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK.
Langenberg C Langenberg Claudia C MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK.
Wareham NJ Wareham Nicholas J NJ MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK.
InterAct Consortium
van Duijn C van Duijn Cornelia C 1] Department of Epidemiology, Subdivision Genetic Epidemiology, Erasmus Medical Center, Postbus 2040, 3000 CA Rotterdam, The Netherlands [2] Center of Medical Systems Biology, Einthovenweg 20, 2333 ZC Leiden, The Netherlands [3] Member of Netherlands Consortium for Healthy Aging sponsored by Netherlands Genomics Initiative, Postbus 9600, 2300 RC Leiden, The Netherlands.
Beilby J Beilby John J 1] PathWest Laboratory Medicine of WA, Nedlands, Western Australia 6009, Australia [2] Schools of Pathology and Laboratory Medicine, and Population Health, The University of Western Australia, Nedlands, Western Australia 6009, Australia.
Pramstaller PP Pramstaller Peter P PP 1] Center for Biomedicine, European Academy of Bolzano/Bozen (EURAC), Via Galvani 31, 39100 Bolzano, Italy [2] Department of Neurology, General Central Hospital, Lorenz-Böhler-Straße, 5, 39100 Bolzano, Italy.
Hicks AA Hicks Andrew A AA Center for Biomedicine, European Academy of Bolzano/Bozen (EURAC), Via Galvani 31, 39100 Bolzano, Italy.
Ouwehand WH Ouwehand Willem H WH 1] Department of Haematology, University of Cambridge, Cambridge Biomedical Campus Box 139, Hills Road, Cambridge CB2 0XY, UK [2] NHS Blood and Transplant, Cambridge Biomedical Campus, Long Road, Cambridge CB2 0PT, UK.
Oexle K Oexle Konrad K Institute of Human Genetics, Klinikum Rechts der Isar, Technische Universität München, Ismaninger Straße 22, 81675 München, Germany.
Gieger C Gieger Christian C 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.
Metspalu A Metspalu Andres A Estonian Genome Center, University of Tartu, Riia 23b, 51010 Tartu, Estonia.
Camaschella C Camaschella Clara C 1] Division of Genetics and Cell Biology, San Raffaele Scientific Institute, 20132 Milano, Italy [2] Vita-Salute University, 20132 Milan, Italy.
Toniolo D Toniolo Daniela D Division of Genetics and Cell Biology, San Raffaele Scientific Institute, 20132 Milano, Italy.
Swinkels DW Swinkels Dorine W DW 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.
Whitfield JB Whitfield John B JB QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4029, Australia.
INVESTIGATORS
LASTNAME FORENAME INITIALS AFFILIATION
Langenberg Claudia C
Scott Robert A RA
Podmore Clara C
Sharp Stephen J SJ
Forouhi Nita G NG
Kerrison Nicola D ND
Sims Matt M
Barroso Inês I
Deloukas Panos P
McCarthy Mark I MI
Arriola Larraitz L
Balkau Beverley B
Barricarte Aurelio A
Schulze Matthias B MB
Meidtner Karina K
Boeing Heiner H
Franks Paul W PW
Gonzalez Carlos C
Grioni Sara S
Kaaks Rudolf R
Key Timothy J TJ
Navarro Carmen C
Nilsson Peter M PM
Overvad Kim K
Palli Domenico D
Panico Salvatore S
Quirós J Ramón J
Rolandsson Olov O
Sacerdote Carlotta C
Sánchez María-José MJ
Slimani Nadia N
Tjonneland Anne A
Tumino Rosario R
van der A Daphne L DL
van der Schouw Yvonne T YT
Riboli Elio E
Wareham Nicholas J NJ
JOURNAL
VOLUME: 5
ISSUE:
TITLE: Nature communications
ISOABBREVIATION: Nat Commun
YEAR: 2014
MONTH:
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 2041-1723
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Nat Commun
COUNTRY: England
ISSNLINKING: 2041-1723
NLMUNIQUEID: 101528555
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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ErratumIn Nat Commun. 2015;6:6542 25817829 Häldin, Jonas [corrected to Hälldin, Jonas]
GRANTS
GRANTID AGENCY COUNTRY
MC_U106179471 Medical Research Council United Kingdom
MC_UU_12015/1 Medical Research Council United Kingdom
R01 AA014041 NIAAA NIH HHS United States
U54 EB020403 NIBIB NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adult
Chromosomes, Human, Pair 7 genetics
Ferritins metabolism
Gene Expression Regulation metabolism
Genetic Association Studies metabolism
Genetic Loci metabolism
Genetic Predisposition to Disease metabolism
Hemochromatosis genetics
Homeostasis genetics
Humans genetics
Iron metabolism
Lipids blood
Phenotype blood
Polymorphism, Single Nucleotide genetics
Reproducibility of Results genetics
Risk Factors genetics
Transferrin metabolism
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 Lipids
0 Transferrin
9007-73-2 Ferritins
E1UOL152H7 Iron
OTHER ID's
OTHERID SOURCE
NIHMS619770 NLM
PMC4215164 NLM