Novel loci and biomedical consequences of iron homoeostasis variation
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.
Main Authors
Format
Articles
Research article
Published
2024
Series
Subjects
Publication in research information system
Publisher
Nature Publishing Group
The permanent address of the publication
https://urn.fi/URN:NBN:fi:jyu-202412117738Use this for linking
Review status
Peer reviewed
ISSN
2399-3642
DOI
https://doi.org/10.1038/s42003-024-07115-3
Language
English
Published in
Communications Biology
Citation
- Popovic, R., Fabre, M., Schutzman, J., Kulkarni, D., Porello, A., Loboda, A., Lehtonen, H., McDonough, S., Vuoti, S., Kaarniranta, K., Turunen, J. A., Ollila, T., Uusitalo, H., Karjalainen, J., Liu, M., Loomis, S., Strauss, E., Chen, H., Tasanen, K., . . . Di Angelantonio, E. (2024). Novel loci and biomedical consequences of iron homoeostasis variation. Communications Biology, 7, Article 1631. https://doi.org/10.1038/s42003-024-07115-3
Additional information about funding
We would like to thank the individuals who participated in the study and whose contribution made this work possible. FinDonor_1 & FinDonor_2. These studies were supported by the Finnish Funding Agency for Technology and Innovation (Tekes) to the Salwe GID (Personalised Diagnostics and Care) programme (ID 3982/31/2013) and by the VTR funding from the Finnish Government. FinnGen. We want to acknowledge the participants and investigators of FinnGen study. The FinnGen project is funded by two grants from Business Finland (HUS 4685/31/2016 and UH 4386/31/2016) and the following industry partners: AbbVie Inc., AstraZeneca UK Ltd, Biogen MA Inc., Bristol Myers Squibb (and Celgene Corporation & Celgene International II Sàrl), Genentech Inc., Merck Sharp & Dohme LCC, Pfizer Inc., GlaxoSmithKline Intellectual Property Development Ltd., Sanofi US Services Inc., Maze Therapeutics Inc., Janssen Biotech Inc, Novartis AG, and Boehringer Ingelheim International GmbH.
Copyright© The Author(s) 2024