Novel loci and biomedical consequences of iron homoeostasis variation

DBDS Genomic Consortium, FinnGen Consortium, Elias Allara, Steven Bell, Feiyi Wang, Aarno Palotie, Mark Daly, Tomi P. Mäkelä, Jaakko Kaprio, Markus Perola, Jukka Partanen, Taneli Raivio, Samuli Ripatti, Olli Carpén, Minna Raivio, Pentti Tienari, Juulia Partanen, Martti Färkkilä, Jukka Koskela, Sampsa PikkarainenKari Eklund, Nina Mars, Paula Kauppi, Felix Vaura, Daniel Gordin, Juha Sinisalo, Marja-Riitta Taskinen, Tiinamaija Tuomi, Timo Hiltunen, Mary Pat Reeve, Sanni Ruotsalainen, Tuomo Meretoja, Heikki Joensuu, Johanna Mattson, Eveliina Salminen, Peeter Karihtala, Esa Pitkänen, Joni A. Turunen, Terhi Ollila, Juha Karjalainen, Katariina Hannula-Jouppi, Pirkko Pussinen, Aino Salminen, Tuula Salo, David Rice, Pekka Nieminen, Ulla Palotie, Hannele Laivuori, Venla Kurra, Oskari Heikinheimo, Ilkka Kalliala, Lauri Aaltonen, Luc Djousse, Kelly Cho, Michael Inouye, Stephen Burgess, Beben Benyamin, Konrad Oexle, Dorine W. Swinkels, Kari Stefansson, Magnus Magnusson, Andrea Ganna, Michael Gaziano, Kerry Ivey, John Danesh, Alexandre Pereira, Angela M. Wood, Adam S. Butterworth, Emanuele Di Angelantonio, Katja Kivinen, Taru Tukiainen, Hanna Ollila, Elmo Saarentaus, Fredrik Åberg, Mitja Kurki, Aki Havulinna, Juha Mehtonen, Priit Palta, Shabbeer Hassan, Pietro Della Briotta Parolo, Susanna Lemmelä, Aoxing Liu, Arto Lehisto, Vincent Llorens, Henrike Heyne, Joel Rämö, Rodosthenis Rodosthenous, Satu Strausz, Jiwoo Lee, Risto Kajanne, Mervi Aavikko, Helen Cooper, Denise Öller, Rasko Leinonen, L. Elisa Lahtela, Mari Kaunisto, Elina Kilpeläinen, Timo P. Sipilä, Oluwaseun Alexander Dada, Awaisa Ghazal, Anastasia Kytölä, Rigbe Weldatsadik, Kati M. Donner, Shuang Luo, Shanmukha Sampath Padmanabhuni, Iiris Hovatta

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Sammanfattning

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.
Originalspråkengelska
Artikelnummer1631
TidskriftCommunications Biology
Volym7
Nummer1
Antal sidor17
ISSN2399-3642
DOI
StatusPublicerad - 2024
MoE-publikationstypA1 Tidskriftsartikel-refererad

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