Exploring the associations of plasma proteins with frailty based on Mendelian randomization

Abstract Background Frailty is an emerging global burden of disease, characterized as an age-related clinical syndrome. Recent studies have suggested a potential link of circulating protein levels with the onset of frailty. This study aims to analyze the potential causal relationships of plasma prot...

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Main Authors: Shuhui Chen, Hao Lin, Bin Liu, Hejing Pan, Yaling Xu, Yingying Mao, Lin Huang
Format: Article
Language:English
Published: BMC 2024-12-01
Series:BMC Immunology
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Online Access:https://doi.org/10.1186/s12865-024-00677-1
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author Shuhui Chen
Hao Lin
Bin Liu
Hejing Pan
Yaling Xu
Yingying Mao
Lin Huang
author_facet Shuhui Chen
Hao Lin
Bin Liu
Hejing Pan
Yaling Xu
Yingying Mao
Lin Huang
author_sort Shuhui Chen
collection DOAJ
description Abstract Background Frailty is an emerging global burden of disease, characterized as an age-related clinical syndrome. Recent studies have suggested a potential link of circulating protein levels with the onset of frailty. This study aims to analyze the potential causal relationships of plasma proteins with frailty using a Mendelian Randomization (MR) study design. Methods Associations of plasma proteins with frailty were assessed using inverse variance weighted (IVW), MR-Egger regression, weighted median, maximum-likelihood method, and MR-PRESSO test. Protein-protein interaction network construction and gene ontology functional enrichment analysis were conducted based on MR-identified target proteins. Results After false discovery rate (FDR) correction, MR analysis identified five plasma proteins, including BIRC2 [OR = 0.978, 95%CI (0.967–0.990)] and PSME1 [OR = 0.936, 95%CI (0.909–0.965)], as protective factors against frailty, and 49 proteins, including APOB [OR = 1.053, 95%CI (1.037–1.069)] and CYP3A4 [OR = 1.098, 95%CI (1.068–1.128)], as risk factors. Network analysis suggested BIRC2, PSME1, APOE, and CTNNB1 as key intervention targets. Conclusion This study employed MR design to investigate the association of circulating plasma proteins with frailty, identified five proteins negatively associated with frailty risk and 49 proteins positively associated with frailty.
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spelling doaj-art-3abbb15da66b40029ef1c32df1f824b22025-08-20T02:43:32ZengBMCBMC Immunology1471-21722024-12-0125111010.1186/s12865-024-00677-1Exploring the associations of plasma proteins with frailty based on Mendelian randomizationShuhui Chen0Hao Lin1Bin Liu2Hejing Pan3Yaling Xu4Yingying Mao5Lin Huang6School of Public Health, Zhejiang Chinese Medical UniversitySchool of Public Health, Zhejiang Chinese Medical UniversitySchool of Public Health, Zhejiang Chinese Medical UniversityCollege of Basic Medical Science, Zhejiang Chinese Medical UniversityCollege of Basic Medical Science, Zhejiang Chinese Medical UniversitySchool of Public Health, Zhejiang Chinese Medical UniversityCollege of Basic Medical Science, Zhejiang Chinese Medical UniversityAbstract Background Frailty is an emerging global burden of disease, characterized as an age-related clinical syndrome. Recent studies have suggested a potential link of circulating protein levels with the onset of frailty. This study aims to analyze the potential causal relationships of plasma proteins with frailty using a Mendelian Randomization (MR) study design. Methods Associations of plasma proteins with frailty were assessed using inverse variance weighted (IVW), MR-Egger regression, weighted median, maximum-likelihood method, and MR-PRESSO test. Protein-protein interaction network construction and gene ontology functional enrichment analysis were conducted based on MR-identified target proteins. Results After false discovery rate (FDR) correction, MR analysis identified five plasma proteins, including BIRC2 [OR = 0.978, 95%CI (0.967–0.990)] and PSME1 [OR = 0.936, 95%CI (0.909–0.965)], as protective factors against frailty, and 49 proteins, including APOB [OR = 1.053, 95%CI (1.037–1.069)] and CYP3A4 [OR = 1.098, 95%CI (1.068–1.128)], as risk factors. Network analysis suggested BIRC2, PSME1, APOE, and CTNNB1 as key intervention targets. Conclusion This study employed MR design to investigate the association of circulating plasma proteins with frailty, identified five proteins negatively associated with frailty risk and 49 proteins positively associated with frailty.https://doi.org/10.1186/s12865-024-00677-1Causal associationFrailtyMendelian randomizationProtein
spellingShingle Shuhui Chen
Hao Lin
Bin Liu
Hejing Pan
Yaling Xu
Yingying Mao
Lin Huang
Exploring the associations of plasma proteins with frailty based on Mendelian randomization
BMC Immunology
Causal association
Frailty
Mendelian randomization
Protein
title Exploring the associations of plasma proteins with frailty based on Mendelian randomization
title_full Exploring the associations of plasma proteins with frailty based on Mendelian randomization
title_fullStr Exploring the associations of plasma proteins with frailty based on Mendelian randomization
title_full_unstemmed Exploring the associations of plasma proteins with frailty based on Mendelian randomization
title_short Exploring the associations of plasma proteins with frailty based on Mendelian randomization
title_sort exploring the associations of plasma proteins with frailty based on mendelian randomization
topic Causal association
Frailty
Mendelian randomization
Protein
url https://doi.org/10.1186/s12865-024-00677-1
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