Novel loci and biomedical consequences of iron homoeostasis variation

Allara, Elias ; Bell, Steven ; Smith, Rebecca; Keene, Spencer J.; Gill, Dipender ; Gaziano, Liam ; Morselli Gysi, Deisy; Wang, Feiyi ; Tragante, Vinicius ; Mason, Amy ; Karthikeyan, Savita; Lumbers, R. Thomas ; Bonglack, Emmanuela; Ouwehand, Willem; Roberts, David J.; Dowsett, Joseph ; Ostrowski, Sisse Rye ; Larsen, Margit Hørup; Ullum, Henrik; Pedersen, Ole Birger ; Brunak, Søren ; Banasik, Karina ; Erikstrup, Christian ; Bay, Jakob; Boldsen, Jens Kjærgaard; Brodersen, Thorsten; Demur, Alfonso Buil; Christoffersen, Lea Arregui Nordahl; Didriksen, Maria; Dinh, Khoa Manh; Erikstrup, Christian; Feenstra, Bjarke; Geller, Frank; Gudbjartsson, Daniel; Hansen, Thomas Folkmann; Helenius Mikkelsen, Dorte; Hindhede, Lotte; Hjalgrim, Henrik; Hjorth von Stemann, Jakob; Jensen, Bitten Aagaard; Schork, Andrew Joseph; Kaspersen, Kathrine; Kjerulff, Bertram Dalskov; Kongstad, Mette; Mikkelsen, Susan; Mikkelsen, Christina; Nissen, Janna; Nyegaard, Mette; Quinn, Liam James Elgaard; Rafnar, Þórunn; Rohde, Palle Duun; Rostgaard, Klaus; Schwinn, Michael; Sørensen, Erik; Stefansson, Kari; Stefánsson, Hreinn; Thørner, Lise Wegner; Þorsteinsdóttir, Unnur; Topholm Bruun, Mie; Werge, Thomas; Westergaard, David; Mitchell, Jonathan; Fuchsberger, Christian; Pattaro, Cristian; Pramstaller, Peter P. ; Girelli, Domenico ; Arvas, Mikko ; Toivonen, Jarkko ; Molnos, Sophie; Peters, Annette ; Polasek, Ozren ; Rudan, Igor; Hayward, Caroline ; McDonnell, Ciara; Pirastu, Nicola ; Wilson, James F. ; Hurk, Katja van den; Quee, Franke; Ferrucci, Luigi ; Bandinelli, Stefania; Tanaka, Toshiko; Girotto, Giorgia ; Concas, Maria Pina ; Pecori, Alessandro; Verweij, Niek; van der Harst, Pim; van de Vegte, Yordi J. ; Kiemeney, Lambertus A. ; Sweep, Fred C. ; Galesloot, Tessel E.; Sulem, Patrick; Gudbjartsson, Daniel; Ferkingstad, Egil; Djousse, Luc; Cho, Kelly; Inouye, Michael ; Burgess, Stephen ; Benyamin, Beben ; Oexle, Konrad; Swinkels, Dorine; Stefansson, Kari; Magnusson, Magnus ; Ganna, Andrea ; Gaziano, Michael; Ivey, Kerry; Danesh, John; Pereira, Alexandre ; Wood, Angela M. ; Butterworth, Adam S. und Di Angelantonio, Emanuele (2024): Novel loci and biomedical consequences of iron homoeostasis variation. In: Communications Biology, Bd. 7, 1631

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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin > Institut für Medizinische Informationsverarbeitung, Biometrie und Epidemiologie
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 2399-3642
• Bemerkung: with the FinnGen Consortium; a complete list of authors can be found within the article
• Sprache: Englisch