Abstract
Original language | English |
---|---|
Article number | 156 |
Journal | Communications Biology |
Volume | 4 |
Issue number | 1 |
Number of pages | 14 |
ISSN | 2399-3642 |
DOIs | |
Publication status | Published - 3 Feb 2021 |
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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 Sølvsten; Eggertsson, Hanne P. ; Howson, Joanna M. M. ; Thørner, Lise W. ; Kristmundsdottir, Snaedis ; Astle, William J. ; Erikstrup, Christian; Sigurdsson, Jon K. ; Vukovic, Dragana; Dinh, Khoa M. ; Tragante, Vinicius ; Surendran, Praveen ; Pedersen, Ole Birger; Vidarsson, Brynja ; Jiang, Tao; Paarup, Helene M.; Onundarson, Pall T. ; Akbari, Parsa ; Nielsen, Kaspar René; 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 ; Folkmann Hansen, Thomas; Sigurdardottir, Olof ; Stefansson, Hreinn ; Rye, David ; Andersen, Steffen; Banasik, Karina; Brunak, Søren; Burgdorf, Kristoffer ; Erikstrup, Christian; Jemec, Gregor Borut Ernst; Jennum, Poul; Johanssond, Pär I.; Nyegaard, Mette; Petersen, Mikkel; Werge, Thomas; Peters, James E. ; Westergaard, David; Holm, Hilma ; Soranzo, Nicole ; Thorleifsson, Gudmar ; Ouwehand, Willem H. ; Thorsteinsdottir, Unnur ; Roberts, David J. ; Sulem, Patrick; Butterworth, Adam S. ; Gudbjartsson, Daniel F. ; Danesh, John ; Brunak, Søren; Angelantonio, Emanuele Di ; Ullum, Henrik; Stefansson, Kari .
In: Communications Biology, Vol. 4, No. 1, 156, 03.02.2021.Research output: Contribution to journal › Journal article › Research › peer-review
TY - JOUR
T1 - A Genome-Wide Meta-Analysis Yields 46 New Loci Associating with Biomarkers of Iron Homeostasis
AU - Bell, Steven
AU - Rigas, Andreas S.
AU - Magnusson, Magnus K.
AU - Ferkingstad, Egil
AU - Allara, Elias
AU - Bjornsdottir, Gyda
AU - Ramond, Anna
AU - Sørensen, Erik
AU - Halldorsson, Gisli H.
AU - Paul, Dirk S.
AU - Burgdorf, Kristoffer Sølvsten
AU - Eggertsson, Hanne P.
AU - Howson, Joanna M. M.
AU - Thørner, Lise W.
AU - Kristmundsdottir, Snaedis
AU - Astle, William J.
AU - Erikstrup, Christian
AU - Sigurdsson, Jon K.
AU - Vukovic, Dragana
AU - Dinh, Khoa M.
AU - Tragante, Vinicius
AU - Surendran, Praveen
AU - Pedersen, Ole Birger
AU - Vidarsson, Brynja
AU - Jiang, Tao
AU - Paarup, Helene M.
AU - Onundarson, Pall T.
AU - Akbari, Parsa
AU - Nielsen, Kaspar René
AU - Lund, Sigrun H.
AU - Juliusson, Kristinn
AU - Magnusson, Magnus I.
AU - Frigge, Michael L.
AU - Oddsson, Asmundur
AU - Olafsson, Isleifur
AU - Kaptoge, Stephen
AU - Hjalgrim, Henrik
AU - Runarsson, Gudmundur
AU - Wood, Angela M.
AU - Jonsdottir, Ingileif
AU - Folkmann Hansen, Thomas
AU - Sigurdardottir, Olof
AU - Stefansson, Hreinn
AU - Rye, David
AU - Andersen, Steffen
AU - Banasik, Karina
AU - Brunak, Søren
AU - Burgdorf, Kristoffer
AU - Erikstrup, Christian
AU - Jemec, Gregor Borut Ernst
AU - Jennum, Poul
AU - Johanssond, Pär I.
AU - Nyegaard, Mette
AU - Petersen, Mikkel
AU - Werge, Thomas
AU - Peters, James E.
AU - Westergaard, David
AU - Holm, Hilma
AU - Soranzo, Nicole
AU - Thorleifsson, Gudmar
AU - Ouwehand, Willem H.
AU - Thorsteinsdottir, Unnur
AU - Roberts, David J.
AU - Sulem, Patrick
AU - Butterworth, Adam S.
AU - Gudbjartsson, Daniel F.
AU - Danesh, John
AU - Brunak, Søren
AU - Angelantonio, Emanuele Di
AU - Ullum, Henrik
AU - Stefansson, Kari
PY - 2021/2/3
Y1 - 2021/2/3
N2 - 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.
AB - 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.
U2 - 10.1038/s42003-020-01575-z
DO - 10.1038/s42003-020-01575-z
M3 - Journal article
VL - 4
JO - Communications Biology
JF - Communications Biology
SN - 2399-3642
IS - 1
M1 - 156
ER -