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DOI 10.1038/s42003-024-07115-3

Медицинская библиотека · Communications biology · 2024

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, DBDS Genomic Consortium, 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, van den Hurk Katja, 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, FinnGen Consortium, 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, Di Angelantonio Emanuele

СтатьяМетаанализПоддержка NIH: внешняя программаПоддержка службы здравоохранения СШАПоддержка исследования: вне правительства СШАПеревод в очереди

Аннотация

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.

Для цитирования: 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, DBDS Genomic Consortium, 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, van den Hurk Katja, 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, FinnGen Consortium, 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, Di Angelantonio Emanuele. Novel loci and biomedical consequences of iron homoeostasis variation.. Communications biology. 2024. DOI: 10.1038/s42003-024-07115-3.

Предметные рубрики MeSH

HumansIronHomeostasisHepcidinsReceptors, TransferrinHemochromatosis ProteinFemaleMendelian Randomization AnalysisMaleGenome-Wide Association StudyPolymorphism, Single Nucleotide
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