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

This paper analyses genetic association data on biochemical markers of iron status from 11 European-population studies, with replication in eight additional...

Authors:
Benyamin B, Esko T, Ried JS, Radhakrishnan A, Vermeulen SH, Traglia M, ... Anderson D, et al.

Authors notes:
Nature Communications. 2014;5:4926

Keywords:
Hemochromatosis, iron overload, genetic association, iron markers, loci

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 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.