TY - JOUR
T1 - Novel loci and biomedical consequences of iron homoeostasis variation
AU - DBDS Genomic Consortium
AU - FinnGen Consortium
AU - Allara, Elias
AU - Bell, Steven
AU - Wang, Feiyi
AU - Palotie, Aarno
AU - Daly, Mark
AU - Mäkelä, Tomi P.
AU - Kaprio, Jaakko
AU - Perola, Markus
AU - Partanen, Jukka
AU - Raivio, Taneli
AU - Ripatti, Samuli
AU - Carpén, Olli
AU - Raivio, Minna
AU - Tienari, Pentti
AU - Partanen, Juulia
AU - Färkkilä, Martti
AU - Koskela, Jukka
AU - Pikkarainen, Sampsa
AU - Eklund, Kari
AU - Mars, Nina
AU - Kauppi, Paula
AU - Vaura, Felix
AU - Gordin, Daniel
AU - Sinisalo, Juha
AU - Taskinen, Marja-Riitta
AU - Tuomi, Tiinamaija
AU - Hiltunen, Timo
AU - Reeve, Mary Pat
AU - Ruotsalainen, Sanni
AU - Meretoja, Tuomo
AU - Joensuu, Heikki
AU - Mattson, Johanna
AU - Salminen, Eveliina
AU - Karihtala, Peeter
AU - Pitkänen, Esa
AU - Turunen, Joni A.
AU - Ollila, Terhi
AU - Karjalainen, Juha
AU - Hannula-Jouppi, Katariina
AU - Pussinen, Pirkko
AU - Salminen, Aino
AU - Salo, Tuula
AU - Rice, David
AU - Nieminen, Pekka
AU - Palotie, Ulla
AU - Laivuori, Hannele
AU - Kurra, Venla
AU - Heikinheimo, Oskari
AU - Kalliala, Ilkka
AU - Aaltonen, Lauri
AU - Djousse, Luc
AU - Cho, Kelly
AU - Inouye, Michael
AU - Burgess, Stephen
AU - Benyamin, Beben
AU - Oexle, Konrad
AU - Swinkels, Dorine W.
AU - Stefansson, Kari
AU - Magnusson, Magnus
AU - Ganna, Andrea
AU - Gaziano, Michael
AU - Ivey, Kerry
AU - Danesh, John
AU - Pereira, Alexandre
AU - Wood, Angela M.
AU - Butterworth, Adam S.
AU - Di Angelantonio, Emanuele
AU - Kivinen, Katja
AU - Tukiainen, Taru
AU - Ollila, Hanna
AU - Saarentaus, Elmo
AU - Åberg, Fredrik
AU - Kurki, Mitja
AU - Havulinna, Aki
AU - Mehtonen, Juha
AU - Palta, Priit
AU - Hassan, Shabbeer
AU - Della Briotta Parolo, Pietro
AU - Lemmelä, Susanna
AU - Liu, Aoxing
AU - Lehisto, Arto
AU - Llorens, Vincent
AU - Heyne, Henrike
AU - Rämö, Joel
AU - Rodosthenous, Rodosthenis
AU - Strausz, Satu
AU - Lee, Jiwoo
AU - Kajanne, Risto
AU - Aavikko, Mervi
AU - Cooper, Helen
AU - Öller, Denise
AU - Leinonen, Rasko
AU - Lahtela, L. Elisa
AU - Kaunisto, Mari
AU - Kilpeläinen, Elina
AU - Sipilä, Timo P.
AU - Dada, Oluwaseun Alexander
AU - Ghazal, Awaisa
AU - Kytölä, Anastasia
AU - Weldatsadik, Rigbe
AU - Donner, Kati M.
AU - Luo, Shuang
AU - Padmanabhuni, Shanmukha Sampath
AU - Hovatta, Iiris
PY - 2024
Y1 - 2024
N2 - 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.
AB - 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.
KW - 3111 Biomedicine
U2 - 10.1038/s42003-024-07115-3
DO - 10.1038/s42003-024-07115-3
M3 - Article
SN - 2399-3642
VL - 7
JO - Communications Biology
JF - Communications Biology
IS - 1
M1 - 1631
ER -