| Literature DB >> 33536631 |
Steven Bell1,2, Andreas S Rigas3, Magnus K Magnusson4,5, Egil Ferkingstad6, Elias Allara1,2, Gyda Bjornsdottir6, Anna Ramond1,2,7, Erik Sørensen3, Gisli H Halldorsson6, Dirk S Paul1,2, Kristoffer S Burgdorf3, Hannes P Eggertsson6, Joanna M M Howson2, Lise W Thørner3, Snaedis Kristmundsdottir6, William J Astle1,2,8,9, Christian Erikstrup10, Jon K Sigurdsson6, Dragana Vuckovic1,9, Khoa M Dinh10, Vinicius Tragante6,11, Praveen Surendran2,12, Ole B Pedersen13, Brynjar Vidarsson14, Tao Jiang1,2,9, Helene M Paarup15, Pall T Onundarson16,17, Parsa Akbari1,2,9, Kaspar R Nielsen18, Sigrun H Lund6, Kristinn Juliusson6, Magnus I Magnusson6, Michael L Frigge6, Asmundur Oddsson6, Isleifur Olafsson19, Stephen Kaptoge1,2, Henrik Hjalgrim20, Gudmundur Runarsson14, Angela M Wood1,2, Ingileif Jonsdottir6,16, Thomas F Hansen21,22,23, Olof Sigurdardottir24, Hreinn Stefansson6, David Rye25, James E Peters2, David Westergaard26, Hilma Holm6, Nicole Soranzo1,9,27, Karina Banasik26, Gudmar Thorleifsson6, Willem H Ouwehand1,9,27,28, Unnur Thorsteinsdottir6,16, David J Roberts1,29,30, Patrick Sulem6, Adam S Butterworth1,2, Daniel F Gudbjartsson6,31, John Danesh1,2,9, Søren Brunak26, Emanuele Di Angelantonio32,33,34, Henrik Ullum35, Kari Stefansson36,37.
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.Entities:
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Year: 2021 PMID： 33536631 PMCID： PMC7859200 DOI： 10.1038/s42003-020-01575-z
Source DB: PubMed Journal: Commun Biol ISSN： 2399-3642