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

Accepted version
Peer-reviewed

Type

Article

Change log

Authors

Benyamin, Beben 
Esko, Tonu 
Ried, Janina S 
Radhakrishnan, Aparna 
Vermeulen, Sita H 

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.

Description

Keywords

Adult, Chromosomes, Human, Pair 7, Ferritins, Gene Expression Regulation, Genetic Association Studies, Genetic Loci, Genetic Predisposition to Disease, Hemochromatosis, Homeostasis, Humans, Iron, Lipids, Phenotype, Polymorphism, Single Nucleotide, Reproducibility of Results, Risk Factors, Transferrin

Journal Title

Nat Commun

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

5

Publisher

Springer Science and Business Media LLC
Sponsorship
Medical Research Council (MC_UU_12015/1)
Wellcome Trust (097451/Z/11/Z)
Medical Research Council (MC_U106179471)
British Heart Foundation (None)
CCF (None)