TY - JOUR
T1 - Novel loci affecting iron homeostasis and their effects in individuals at risk for hemochromatosis
AU - Benyamin, Beben
AU - Esko, Tonu
AU - Ried, Janina S
AU - Radhakrishnan, Aparna
AU - Vermeulen, Sita H
AU - Traglia, Michela
AU - Gögele, Martin
AU - Anderson, Denise
AU - Broer, Linda
AU - Podmore, Clara
AU - Luan, Jian'an
AU - Kutalik, Zoltan
AU - Sanna, Serena
AU - van der Meer, Peter
AU - Tanaka, Toshiko
AU - Wang, Fudi
AU - Westra, Harm-Jan
AU - Franke, Lude
AU - Mihailov, Evelin
AU - Milani, Lili
AU - Hälldin, Jonas
AU - Häldin, Jonas
AU - Winkelmann, Juliane
AU - Meitinger, Thomas
AU - Thiery, Joachim
AU - Peters, Annette
AU - Waldenberger, Melanie
AU - Rendon, Augusto
AU - Jolley, Jennifer
AU - Sambrook, Jennifer
AU - Kiemeney, Lambertus A
AU - Sweep, Fred C
AU - Sala, Cinzia F
AU - Schwienbacher, Christine
AU - Pichler, Irene
AU - Hui, Jennie
AU - Demirkan, Ayse
AU - Isaacs, Aaron
AU - Amin, Najaf
AU - Steri, Maristella
AU - Waeber, Gérard
AU - Verweij, Niek
AU - Powell, Joseph E
AU - Nyholt, Dale R
AU - Heath, Andrew C
AU - Madden, Pamela A F
AU - Visscher, Peter M
AU - Wright, Margaret J
AU - Montgomery, Grant W
AU - van der Harst, Pim
PY - 2014/10/29
Y1 - 2014/10/29
N2 - 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.
AB - 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.
KW - Adult
KW - Chromosomes, Human, Pair 7/genetics
KW - Ferritins/metabolism
KW - Gene Expression Regulation
KW - Genetic Association Studies
KW - Genetic Loci
KW - Genetic Predisposition to Disease
KW - Hemochromatosis/blood
KW - Homeostasis/genetics
KW - Humans
KW - Iron/blood
KW - Lipids/blood
KW - Phenotype
KW - Polymorphism, Single Nucleotide/genetics
KW - Reproducibility of Results
KW - Risk Factors
KW - Transferrin/metabolism
U2 - 10.1038/ncomms5926
DO - 10.1038/ncomms5926
M3 - Article
C2 - 25352340
SN - 2041-1723
VL - 5
SP - 4926
JO - Nature Communications
JF - Nature Communications
ER -