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Allara, E.* ; Bell, S.* ; Smith, R.* ; Keene, S.J.* ; Gill, D.* ; Gaziano, L.* ; Morselli Gysi, D.* ; Wang, F.* ; Tragante, V.* ; Mason, A.* ; Karthikeyan, S.* ; Lumbers, R.T.* ; Bonglack, E.* ; Ouwehand, W.* ; Roberts, D.J.* ; Dowsett, J.* ; Ostrowski, S.R.* ; Larsen, M.H.* ; Ullum, H.* ; Pedersen, O.B.* ; Brunak, S.* ; Banasik, K.* ; Erikstrup, C.* ; Mitchell, J.* ; Fuchsberger, C.* ; Pattaro, C.* ; Pramstaller, P.P.* ; Girelli, D.* ; Arvas, M.* ; Toivonen, J.* ; Molnos, S. ; Peters, A. ; Polasek, O.* ; Rudan, I.* ; Hayward, C.* ; McDonnell, C.* ; Pirastu, N.* ; Wilson, J.F.* ; van den Hurk, K.* ; Quee, F.* ; Ferrucci, L.* ; Bandinelli, S.* ; Tanaka, T.* ; Girotto, G.* ; Concas, M.P.* ; Pecori, A.* ; Verweij, N.* ; van der Harst, P.* ; van de Vegte, Y.J.* ; Kiemeney, L.A.* ; Sweep, F.C.* ; Galesloot, T.E.* ; Sulem, P.* ; Gudbjartsson, D.* ; Ferkingstad, E.* ; Djousse, L.* ; Cho, K.* ; Inouye, M.* ; Burgess, S.* ; Benyamin, B.* ; Oexle, K. ; Swinkels, D.W.* ; Stefansson, K.* ; Magnusson, M.* ; Ganna, A.* ; Gaziano, M.* ; Ivey, K.* ; Danesh, J.* ; Pereira, A.* ; Wood, A.M.* ; Butterworth, A.S.* ; di Angelantonio, E.*

Novel loci and biomedical consequences of iron homoeostasis variation.

Comm. Biol. 7:1631 (2024)
Publ. Version/Full Text DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
ISSN (print) / ISBN 2399-3642
e-ISSN 2399-3642
Journal Communications Biology
Quellenangaben Volume: 7, Issue: 1, Pages: , Article Number: 1631 Supplement: ,
Publisher Springer
Publishing Place London
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology II (EPI2)
Institute of Neurogenomics (ING)