A genome-wide meta-analysis yields 46 new loci associating with biomarkers of iron homeostasis
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)...
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ftpubmed:oai:pubmedcentral.nih.gov:7859200 2023-05-15T16:50:08+02:00 A genome-wide meta-analysis yields 46 new loci associating with biomarkers of iron homeostasis Bell, Steven Rigas, Andreas S. Magnusson, Magnus K. Ferkingstad, Egil Allara, Elias Bjornsdottir, Gyda Ramond, Anna Sørensen, Erik Halldorsson, Gisli H. Paul, Dirk S. Burgdorf, Kristoffer S. Eggertsson, Hannes P. Howson, Joanna M. M. Thørner, Lise W. Kristmundsdottir, Snaedis Astle, William J. Erikstrup, Christian Sigurdsson, Jon K. Vuckovic, Dragana Dinh, Khoa M. Tragante, Vinicius Surendran, Praveen Pedersen, Ole B. Vidarsson, Brynjar Jiang, Tao Paarup, Helene M. Onundarson, Pall T. Akbari, Parsa Nielsen, Kaspar R. Lund, Sigrun H. Juliusson, Kristinn Magnusson, Magnus I. Frigge, Michael L. Oddsson, Asmundur Olafsson, Isleifur Kaptoge, Stephen Hjalgrim, Henrik Runarsson, Gudmundur Wood, Angela M. Jonsdottir, Ingileif Hansen, Thomas F. Sigurdardottir, Olof Stefansson, Hreinn Rye, David Peters, James E. Westergaard, David Holm, Hilma Soranzo, Nicole Banasik, Karina Thorleifsson, Gudmar 2021-02-03 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859200/ http://www.ncbi.nlm.nih.gov/pubmed/33536631 https://doi.org/10.1038/s42003-020-01575-z en eng Nature Publishing Group UK http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859200/ http://www.ncbi.nlm.nih.gov/pubmed/33536631 http://dx.doi.org/10.1038/s42003-020-01575-z © The Author(s) 2021 Open Access 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/. CC-BY Commun Biol Article Text 2021 ftpubmed https://doi.org/10.1038/s42003-020-01575-z 2021-02-14T01:25:47Z 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. Text Iceland PubMed Central (PMC) Communications Biology 4 1 |
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Article Bell, Steven Rigas, Andreas S. Magnusson, Magnus K. Ferkingstad, Egil Allara, Elias Bjornsdottir, Gyda Ramond, Anna Sørensen, Erik Halldorsson, Gisli H. Paul, Dirk S. Burgdorf, Kristoffer S. Eggertsson, Hannes P. Howson, Joanna M. M. Thørner, Lise W. Kristmundsdottir, Snaedis Astle, William J. Erikstrup, Christian Sigurdsson, Jon K. Vuckovic, Dragana Dinh, Khoa M. Tragante, Vinicius Surendran, Praveen Pedersen, Ole B. Vidarsson, Brynjar Jiang, Tao Paarup, Helene M. Onundarson, Pall T. Akbari, Parsa Nielsen, Kaspar R. Lund, Sigrun H. Juliusson, Kristinn Magnusson, Magnus I. Frigge, Michael L. Oddsson, Asmundur Olafsson, Isleifur Kaptoge, Stephen Hjalgrim, Henrik Runarsson, Gudmundur Wood, Angela M. Jonsdottir, Ingileif Hansen, Thomas F. Sigurdardottir, Olof Stefansson, Hreinn Rye, David Peters, James E. Westergaard, David Holm, Hilma Soranzo, Nicole Banasik, Karina Thorleifsson, Gudmar A genome-wide meta-analysis yields 46 new loci associating with biomarkers of iron homeostasis |
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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. |
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Bell, Steven Rigas, Andreas S. Magnusson, Magnus K. Ferkingstad, Egil Allara, Elias Bjornsdottir, Gyda Ramond, Anna Sørensen, Erik Halldorsson, Gisli H. Paul, Dirk S. Burgdorf, Kristoffer S. Eggertsson, Hannes P. Howson, Joanna M. M. Thørner, Lise W. Kristmundsdottir, Snaedis Astle, William J. Erikstrup, Christian Sigurdsson, Jon K. Vuckovic, Dragana Dinh, Khoa M. Tragante, Vinicius Surendran, Praveen Pedersen, Ole B. Vidarsson, Brynjar Jiang, Tao Paarup, Helene M. Onundarson, Pall T. Akbari, Parsa Nielsen, Kaspar R. Lund, Sigrun H. Juliusson, Kristinn Magnusson, Magnus I. Frigge, Michael L. Oddsson, Asmundur Olafsson, Isleifur Kaptoge, Stephen Hjalgrim, Henrik Runarsson, Gudmundur Wood, Angela M. Jonsdottir, Ingileif Hansen, Thomas F. Sigurdardottir, Olof Stefansson, Hreinn Rye, David Peters, James E. Westergaard, David Holm, Hilma Soranzo, Nicole Banasik, Karina Thorleifsson, Gudmar |
author_facet |
Bell, Steven Rigas, Andreas S. Magnusson, Magnus K. Ferkingstad, Egil Allara, Elias Bjornsdottir, Gyda Ramond, Anna Sørensen, Erik Halldorsson, Gisli H. Paul, Dirk S. Burgdorf, Kristoffer S. Eggertsson, Hannes P. Howson, Joanna M. M. Thørner, Lise W. Kristmundsdottir, Snaedis Astle, William J. Erikstrup, Christian Sigurdsson, Jon K. Vuckovic, Dragana Dinh, Khoa M. Tragante, Vinicius Surendran, Praveen Pedersen, Ole B. Vidarsson, Brynjar Jiang, Tao Paarup, Helene M. Onundarson, Pall T. Akbari, Parsa Nielsen, Kaspar R. Lund, Sigrun H. Juliusson, Kristinn Magnusson, Magnus I. Frigge, Michael L. Oddsson, Asmundur Olafsson, Isleifur Kaptoge, Stephen Hjalgrim, Henrik Runarsson, Gudmundur Wood, Angela M. Jonsdottir, Ingileif Hansen, Thomas F. Sigurdardottir, Olof Stefansson, Hreinn Rye, David Peters, James E. Westergaard, David Holm, Hilma Soranzo, Nicole Banasik, Karina Thorleifsson, Gudmar |
author_sort |
Bell, Steven |
title |
A genome-wide meta-analysis yields 46 new loci associating with biomarkers of iron homeostasis |
title_short |
A genome-wide meta-analysis yields 46 new loci associating with biomarkers of iron homeostasis |
title_full |
A genome-wide meta-analysis yields 46 new loci associating with biomarkers of iron homeostasis |
title_fullStr |
A genome-wide meta-analysis yields 46 new loci associating with biomarkers of iron homeostasis |
title_full_unstemmed |
A genome-wide meta-analysis yields 46 new loci associating with biomarkers of iron homeostasis |
title_sort |
genome-wide meta-analysis yields 46 new loci associating with biomarkers of iron homeostasis |
publisher |
Nature Publishing Group UK |
publishDate |
2021 |
url |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859200/ http://www.ncbi.nlm.nih.gov/pubmed/33536631 https://doi.org/10.1038/s42003-020-01575-z |
genre |
Iceland |
genre_facet |
Iceland |
op_source |
Commun Biol |
op_relation |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859200/ http://www.ncbi.nlm.nih.gov/pubmed/33536631 http://dx.doi.org/10.1038/s42003-020-01575-z |
op_rights |
© The Author(s) 2021 Open Access 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/. |
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CC-BY |
op_doi |
https://doi.org/10.1038/s42003-020-01575-z |
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