A genome-wide meta-analysis yields 46 new loci associating with biomarkers of iron homeostasis
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...
Published in: | Communications Biology |
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Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
Other Authors: | , , |
Format: | Article in Journal/Newspaper |
Language: | English |
Published: |
Springer Science and Business Media LLC
2021
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Subjects: | |
Online Access: | http://dx.doi.org/10.1038/s42003-020-01575-z http://www.nature.com/articles/s42003-020-01575-z.pdf http://www.nature.com/articles/s42003-020-01575-z |
Summary: | 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. |
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