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Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
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TY - JOUR
T1 - The predictive, preventive, and personalized medicine of multiple sclerosis
T2 - ferroptosis and circulating proteins
AU - Xiong, Yao
AU - Yang, Daifeng
AU - Cai, Shanshan
PY - 2025/8/14
Y1 - 2025/8/14
N2 - ObjectiveBased on the principles of Predictive, Preventive, and Personalized Medicine (PPPM), this study aimed to identify ferroptosis-related genes associated with multiple sclerosis (MS) and to explore the underlying mechanisms through genetic approaches.Materials and MethodsSummary statistics of circulating proteins were obtained from the UK Biobank Pharma Proteomics Project (UKB-PPP), ferroptosis-related genes were curated from the FerrDb database, and MS genome-wide association study (GWAS) data were sourced from the International Multiple Sclerosis Genetics Consortium (IMSGC). Two-sample Mendelian randomization (MR) analyses were performed to assess the causal relationships between proteins, ferroptosis-related genes, and MS risk. Mediation MR analysis was conducted to explore the potential mediating role of ferroptosis-related genes. The primary analytical method was inverse variance weighting (IVW), supplemented by MR-Egger and weighted median approaches.ResultsAfter Bonferroni correction, one ferroptosis-related gene (Ferritin Mitochondrial, FTMT) and 21 circulating proteins were significantly associated with MS. Eleven protein-gene pairs were identified. Mediation analysis further revealed that FTMT mediated the effects of several proteins on MS risk, including CD8A (17.6%), CFB (9.0%), ENPP6 (9.5%), GZMA (22.9%), KIR2DL2 (17.4%), KIR2DL3 (16.9%), and TNXB (13.2%).ConclusionsThis study highlights the critical role of FTMT in linking circulating proteins to MS pathogenesis through ferroptosis regulation, providing novel insights into predictive, preventive, and personalized medicine strategies for MS management.
AB - ObjectiveBased on the principles of Predictive, Preventive, and Personalized Medicine (PPPM), this study aimed to identify ferroptosis-related genes associated with multiple sclerosis (MS) and to explore the underlying mechanisms through genetic approaches.Materials and MethodsSummary statistics of circulating proteins were obtained from the UK Biobank Pharma Proteomics Project (UKB-PPP), ferroptosis-related genes were curated from the FerrDb database, and MS genome-wide association study (GWAS) data were sourced from the International Multiple Sclerosis Genetics Consortium (IMSGC). Two-sample Mendelian randomization (MR) analyses were performed to assess the causal relationships between proteins, ferroptosis-related genes, and MS risk. Mediation MR analysis was conducted to explore the potential mediating role of ferroptosis-related genes. The primary analytical method was inverse variance weighting (IVW), supplemented by MR-Egger and weighted median approaches.ResultsAfter Bonferroni correction, one ferroptosis-related gene (Ferritin Mitochondrial, FTMT) and 21 circulating proteins were significantly associated with MS. Eleven protein-gene pairs were identified. Mediation analysis further revealed that FTMT mediated the effects of several proteins on MS risk, including CD8A (17.6%), CFB (9.0%), ENPP6 (9.5%), GZMA (22.9%), KIR2DL2 (17.4%), KIR2DL3 (16.9%), and TNXB (13.2%).ConclusionsThis study highlights the critical role of FTMT in linking circulating proteins to MS pathogenesis through ferroptosis regulation, providing novel insights into predictive, preventive, and personalized medicine strategies for MS management.
U2 - 10.1080/01616412.2025.2541908
DO - 10.1080/01616412.2025.2541908
M3 - Journal article
JO - Neurological Research
JF - Neurological Research
SN - 0161-6412
ER -