| Title: |
Novel loci and biomedical consequences of iron homoeostasis variation |
| Authors: |
DBDS Genomic Consortium; FinnGen Consortium; Allara, Elias; Bell, Steven; Wang, Feiyi; Palotie, Aarno; Daly, Mark; Mäkelä, Tomi P.; Kaprio, Jaakko; Perola, Markus; Partanen, Jukka; Raivio, Taneli; Ripatti, Samuli; Carpén, Olli; Raivio, Minna; Tienari, Pentti; Partanen, Juulia; Färkkilä, Martti; Koskela, Jukka; Pikkarainen, Sampsa; Eklund, Kari; Mars, Nina; Kauppi, Paula; Vaura, Felix; Gordin, Daniel; Sinisalo, Juha; Taskinen, Marja-Riitta; Tuomi, Tiinamaija; Hiltunen, Timo; Reeve, Mary Pat; Ruotsalainen, Sanni; Meretoja, Tuomo; Joensuu, Heikki; Mattson, Johanna; Salminen, Eveliina; Karihtala, Peeter; Pitkänen, Esa; Turunen, Joni A.; Ollila, Terhi; Karjalainen, Juha; Hannula-Jouppi, Katariina; Pussinen, Pirkko; Salminen, Aino; Salo, Tuula; Rice, David; Nieminen, Pekka; Palotie, Ulla; Laivuori, Hannele; Kurra, Venla; Heikinheimo, Oskari; Kalliala, Ilkka; Aaltonen, Lauri; Djousse, Luc; Cho, Kelly; Inouye, Michael; Burgess, Stephen; Benyamin, Beben; Oexle, Konrad; Swinkels, Dorine W.; Stefansson, Kari; Magnusson, Magnus; Ganna, Andrea; Gaziano, Michael; Ivey, Kerry; Danesh, John; Pereira, Alexandre; Wood, Angela M.; Butterworth, Adam S.; Di Angelantonio, Emanuele; Kivinen, Katja; Tukiainen, Taru; Ollila, Hanna; Saarentaus, Elmo; Åberg, Fredrik; Kurki, Mitja; Havulinna, Aki; Mehtonen, Juha; Palta, Priit; Hassan, Shabbeer; Della Briotta Parolo, Pietro; Lemmelä, Susanna; Liu, Aoxing; Lehisto, Arto; Llorens, Vincent; Heyne, Henrike; Rämö, Joel; Rodosthenous, Rodosthenis; Strausz, Satu; Lee, Jiwoo; Kajanne, Risto; Aavikko, Mervi; Cooper, Helen; Öller, Denise; Leinonen, Rasko; Lahtela, L. Elisa; Kaunisto, Mari; Kilpeläinen, Elina; Sipilä, Timo P.; Dada, Oluwaseun Alexander; Ghazal, Awaisa; Kytölä, Anastasia; Weldatsadik, Rigbe; Donner, Kati M.; Luo, Shuang; Padmanabhuni, Shanmukha Sampath; Hovatta, Iiris; Mäkitie, Antti; Arvas, Mikko; Toivonen, Jarkko |
| Contributors: |
Institute for Molecular Medicine Finland; Centre of Excellence in Complex Disease Genetics; Research Programs Unit; Aarno Palotie / Principal Investigator; Genomics of Neurological and Neuropsychiatric Disorders; Helsinki Institute of Life Science HiLIFE; Department of Biochemistry and Developmental Biology; Mäkelä Lab; University of Helsinki; Department of Physiology; Bio Bank; HUS Group; Department of Public Health; Samuli Olli Ripatti / Principal Investigator; Complex Disease Genetics; HUSLAB; Precision Cancer Pathology; Department of Pathology; Olli Mikael Carpen / Principal Investigator; HUS Radiology and Pathology; Clinicum; HUS Neurocenter; Department of Neurosciences; HUS Abdominal Center; Department of Medicine; HUS Inflammation Center; HUS Heart and Lung Center; Marja-Riitta Taskinen Research Group; Tiinamaija Tuomi Research Group; HUS Comprehensive Cancer Center; Department of Surgery; Department of Oncology; Heikki Joensuu / Principal Investigator; HUS Physiology, Genetics and Preanalytics; Machine learning in biomedicine; HUS Head and Neck Center; Department of Dermatology, Allergology and Venereology; Department of Oral and Maxillofacial Diseases; Medicum; Doctoral Programme in Oral Sciences; David Paul Cracroft Rice / Principal Investigator; HUS Gynecology and Obstetrics; Department of Obstetrics and Gynecology; Lauri Antti Aaltonen / Principal Investigator; Department of Medical and Clinical Genetics; Data Science Genetic Epidemiology Lab; Genomics of Sex Differences; Department of Molecular and Integrative Biosciences; IV kirurgian klinikka; Molecular Systems Biology; Mind and Matter; Department of Psychology; Iiris Hovatta / Principal Investigator; Genetics; Korva-, nenä- ja kurkkutautien klinikka; Finnish Red Cross Blood Service |
| Publisher Information: |
Springer |
| Publication Year: |
2025 |
| Collection: |
Helsingfors Universitet: HELDA – Helsingin yliopiston digitaalinen arkisto |
| Subject Terms: |
Biomedicine |
| Description: |
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. ; Peer reviewed |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
RIS: urn:5B4F346F7A99FED4F8F77C21DCE819CA; RIS: Allara2024; https://hdl.handle.net/10138/590053; 85211476953; 001385774900001 |
| Availability: |
https://hdl.handle.net/10138/590053 |
| Rights: |
cc_by ; info:eu-repo/semantics/openAccess ; openAccess |
| Accession Number: |
edsbas.D34BFB90 |
| Database: |
BASE |