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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
Free journal
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
Keywords Coronary-heart-disease; Ferric Carboxymaltose; Risk; Deficiency; Failure; Metaanalysis; Association; Biobank; Stores; Mice
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 (EPI)
Institute of Neurogenomics (ING)
Grants British Heart Foundation
Department of Innovation, Research
University of the Autonomous Province of Bolzano-South Tyrol
EuropeanRegionalDevelopment Fund
LURM Research Facility at the University Hospital of Verona
Medical Research Council (UK)
European Commission
Republic ofCroatia Ministry of Science, Education, and Sports
anMRC Human Genetics Unit programme grant, 'Quantitative traits in health and disease'
Danish Council for IndependentResearch
Bio-andGenome BankDenmark
The Danish Council for IndependentResearch
Novo Nordisk Foundation
Finnish Funding Agency for Technology and Innovation (Tekes)
VTR funding from the Finnish Government
Business Finland
Innovative Medicines Initiative-2 Joint Undertaking
NIHR
National Institute for Health and Care Research (NIHR) Cambridge Biomedical Research Centre
UK Medical Research Council
Engineering and Physical Sciences Research Council
Economic and Social Research Council
Department of Health and Social Care (England)
Chief Scientist Office of the Scottish Government Health and Social Care Directorates
Health and Social Care Research and Development Division (Welsh Government)
Public Health Agency (Northern Ireland)
Wellcome
Cancer Research UK
NIHR Blood and Transplant Research Unit (BTRU) in Donor Health and Behaviour
Rhodes Trust
Wellcome Trust
United KingdomResearch and InnovationMedical Research Council
National Institute for Health Research Cambridge Biomedical Research Centre
AbbVie Inc.
The Italian Ministry of Health
NIHR Blood and Transplant Research Unit in Donor Health and Genomics
BritishHeart Foundation
NIHRCambridgeBRC
Helmholtz Zentrum Munchen-German Research Center for Environmental Health - German Federal Ministry of Education and Research (BMBF)
State of Bavaria
Munich Center of Health Sciences (MC-Health), Ludwig-Maximilians-Universitat, as part of LMUinnovativ
Dutch Kidney Foundation
EU
National Institutes of Health
Netherlands organisation for health research and development (NWO-Groot grant )
Dutch Inter University Cardiology Institute Netherlands (ICIN)
Telethon, Italy
Ministry ofHealth
AstraZeneca UK Ltd
Biogen MA Inc.
Bristol Myers Squibb
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
Boehringer Ingelheim International GmbH
Italian Ministry of Health
U.S. National Institute on Aging
Compagnia di San Paolo, Torino, Italy
Fondazione Cariplo, Italy
NWO VENI grant