|
PMID |
|
|
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. |
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DATE PUBLISHED |
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HISTORY |
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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 |
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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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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 |
|
|