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A genome-wide meta-analysis yields 46 new loci associating with biomarkers of iron homeostasis
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A genome-wide meta-analysis yields 46 new loci associating with biomarkers of iron homeostasis.pdf | Published version | 2.87 MB | Adobe PDF | View/Open |
iron_supplementary_figures.pdf | Supporting information | 1.4 MB | Adobe PDF | View/Open |
Title: | A genome-wide meta-analysis yields 46 new loci associating with biomarkers of iron homeostasis |
Authors: | Bell, S Rigas, AS Magnusson, MK Ferkingstad, E Allara, E Bjornsdottir, G Ramond, A Sorensen, E Halldorsson, GH Paul, DS Eggertsson, HP Burgdorf, KS Howson, JMM Thorner, LW Kristmundsdottir, S Astle, WJ Erikstrup, C Sigurdsson, JK Vuckovic, D Dinh, KM Tragante, V Surendran, P Pedersen, OB Vidarsson, B Jiang, T Paarup, HM Onundarson, PT Akbari, P Nielsen, KR Lund, SH Juliusson, K Magnusson, M Frigge, ML Oddsson, A Olafsson, I Kaptoge, S Hjalgrim, H Runarsson, G Wood, AM Jonsdottir, I Hansen, TF Sigurdardottir, O Stefansson, H Rye, D Peters, JE Westergaard, D Holm, H Soranzo, N Banasik, K Thorleifsson, G Ouwehand, WH Thorsteinsdottir, U Roberts, DJ Sulem, P Butterworth, AS Gudbjartsson, DF Danesh, J Brunak, S Di Angelantonio, E Ullum, H Stefansson, K |
Item Type: | Journal Article |
Abstract: | Iron is essential for many biological functions and iron deficiency and overload have major health implications. We performed a meta-analysis of three genome-wide association studies from Iceland, the UK and Denmark of blood levels of ferritin (N = 246,139), total iron binding capacity (N = 135,430), iron (N = 163,511) and transferrin saturation (N = 131,471). We found 62 independent sequence variants associating with iron homeostasis parameters at 56 loci, including 46 novel loci. Variants at DUOX2, F5, SLC11A2 and TMPRSS6 associate with iron deficiency anemia, while variants at TF, HFE, TFR2 and TMPRSS6 associate with iron overload. A HBS1L-MYB intergenic region variant associates both with increased risk of iron overload and reduced risk of iron deficiency anemia. The DUOX2 missense variant is present in 14% of the population, associates with all iron homeostasis biomarkers, and increases the risk of iron deficiency anemia by 29%. The associations implicate proteins contributing to the main physiological processes involved in iron homeostasis: iron sensing and storage, inflammation, absorption of iron from the gut, iron recycling, erythropoiesis and bleeding/menstruation. |
Issue Date: | 3-Feb-2021 |
Date of Acceptance: | 7-Dec-2020 |
URI: | http://hdl.handle.net/10044/1/87856 |
DOI: | 10.1038/s42003-020-01575-z |
ISSN: | 2399-3642 |
Publisher: | Nature Research |
Start Page: | 1 |
End Page: | 14 |
Journal / Book Title: | Communications Biology |
Volume: | 4 |
Issue: | 1 |
Copyright Statement: | © The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
Sponsor/Funder: | United Kingdom Research and Innovation |
Funder's Grant Number: | MR/S004068/1 |
Keywords: | Science & Technology Life Sciences & Biomedicine Biology Multidisciplinary Sciences Life Sciences & Biomedicine - Other Topics Science & Technology - Other Topics DBDS Genomic Consortium Science & Technology Life Sciences & Biomedicine Biology Multidisciplinary Sciences Life Sciences & Biomedicine - Other Topics Science & Technology - Other Topics |
Publication Status: | Published |
Article Number: | ARTN 156 |
Online Publication Date: | 2021-02-03 |
Appears in Collections: | Department of Immunology and Inflammation Faculty of Medicine School of Public Health |
This item is licensed under a Creative Commons License