A genome-wide meta-analysis yields 46 new loci associating with biomarkers of iron homeostasis.
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
03 02 2021
03 02 2021
Historique:
received:
19
05
2020
accepted:
07
12
2020
entrez:
4
2
2021
pubmed:
5
2
2021
medline:
10
8
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 33536631
doi: 10.1038/s42003-020-01575-z
pii: 10.1038/s42003-020-01575-z
pmc: PMC7859200
doi:
Substances chimiques
Biomarkers
0
Transferrin
0
Ferritins
9007-73-2
Iron
E1UOL152H7
Types de publication
Journal Article
Meta-Analysis
Multicenter Study
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
156Subventions
Organisme : Medical Research Council
ID : MR/L003120/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_17228
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/S003746/1
Pays : United Kingdom
Organisme : Department of Health
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : British Heart Foundation
ID : RG/18/13/33946
Pays : United Kingdom
Organisme : British Heart Foundation
ID : SP/09/002
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_QA137853
Pays : United Kingdom
Organisme : British Heart Foundation
ID : RG/13/13/30194
Pays : United Kingdom
Organisme : British Heart Foundation
ID : CH/12/2/29428
Pays : United Kingdom
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