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, 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, 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
BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
NIHR Blood and Transplant Research Unit in Donor Health and Behaviour, Cambridge, UK.
Commun Biol. 2024 Dec 6;7(1):1631. doi: 10.1038/s42003-024-07115-3.
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.
铁稳态受到严格调控，其中铁调素和可溶性转铁蛋白受体（sTfR）发挥着重要作用。然而，这些性状的遗传决定因素以及铁稳态变化的生物医学后果尚不清楚。在一项对12个队列、91675名参与者的荟萃分析中，我们发现43个与铁调素或sTfR浓度相关的基因组位点，其中15个此前未被报道。映射到假定基因表明其参与铁性状表达、红细胞生成、免疫反应和细胞运输。对1492717名参与者的292种疾病结局进行孟德尔随机化分析，揭示了铁相关位点和铁状态与多个领域选定健康结局之间的关联。这些关联主要由HFE驱动，HFE与最大的铁变化相关。我们的研究结果增进了对铁稳态及其生物医学后果的理解，表明终生暴露于较高铁水平可能与贫血相关疾病的较低风险以及泌尿生殖系统、肌肉骨骼、感染性和肿瘤性疾病的较高风险相关。
Zotero 插件
