| Title: | Novel loci and biomedical consequences of iron homoeostasis variation |
| Journal: | Communications Biology |
| Published: | 6 Dec 2024 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/39643614/ |
| DOI: | https://doi.org/10.1038/s42003-024-07115-3 |
Publication 14044
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Abstract
Iron homoeostasis is tightly regulated, with hepcidin and soluble transferrin receptor (sTfR) playing significant roles. However, the genetic determinants of these traits and the biomedical consequences of iron homoeostasis variation are unclear. In a meta-analysis of 12 cohorts involving 91,675 participants, we found 43 genomic loci associated with either hepcidin or sTfR concentration, of which 15 previously unreported. Mapping to putative genes indicated involvement in iron-trait expression, erythropoiesis, immune response and cellular trafficking. Mendelian randomisation of 292 disease outcomes in 1,492,717 participants revealed associations of iron-related loci and iron status with selected health outcomes across multiple domains. These associations were largely driven by HFE, which was associated with the largest iron variation. Our findings enhance understanding of iron homoeostasis and its biomedical consequences, suggesting that lifelong exposure to higher iron levels is likely associated with lower risk of anaemia-related disorders and higher risk of genitourinary, musculoskeletal, infectious and neoplastic diseases.</p>
11 Keywords
- Female
- Genome-Wide Association Study
- Hemochromatosis Protein
- Hepcidins
- Homeostasis
- Humans
- Iron
- Male
- Mendelian Randomization Analysis
- Polymorphism, Single Nucleotide
- Receptors, Transferrin
72 Authors
- Elias Allara
- Steven Bell
- Rebecca Smith
- Spencer J. Keene
- Dipender Gill
- Liam Gaziano
- Deisy Morselli Gysi
- Feiyi Wang
- Vinicius Tragante
- Amy Mason
- Savita Karthikeyan
- R. Thomas Lumbers
- Emmanuela Bonglack
- Willem Ouwehand
- David J. Roberts
- Joseph Dowsett
- Sisse Rye Ostrowski
- Margit Hørup Larsen
- Henrik Ullum
- Ole Birger Pedersen
- Søren Brunak
- Karina Banasik
- Christian Erikstrup
- Jonathan Mitchell
- Christian Fuchsberger
- Cristian Pattaro
- Peter P. Pramstaller
- Domenico Girelli
- Mikko Arvas
- Jarkko Toivonen
- Sophie Molnos
- Annette Peters
- Ozren Polasek
- Igor Rudan
- Caroline Hayward
- Ciara McDonnell
- Nicola Pirastu
- James F. Wilson
- Katja van den Hurk
- Franke Quee
- Luigi Ferrucci
- Stefania Bandinelli
- Toshiko Tanaka
- Giorgia Girotto
- Maria Pina Concas
- Alessandro Pecori
- Niek Verweij
- Pim van der Harst
- Yordi J. van de Vegte
- Lambertus A. Kiemeney
- Fred C. Sweep
- Tessel E. Galesloot
- Patrick Sulem
- Daniel Gudbjartsson
- Egil Ferkingstad
- Luc Djousse
- Kelly Cho
- Michael Inouye
- Stephen Burgess
- Beben Benyamin
- Konrad Oexle
- Dorine Swinkels
- Kari Stefansson
- Magnus Magnusson
- Andrea Ganna
- Michael Gaziano
- Kerry Ivey
- John Danesh
- Alexandre Pereira
- Angela M. Wood
- Adam S. Butterworth
- Emanuele Di Angelantonio
1 Application
| Application ID | Title |
|---|---|
| 88349 | Genetic factors underlying the association between cardiovascular health and circulating protein and metabolite levels |
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