1. Therapeutic targets for muscle weakness in older adults: proteome-wide Mendelian randomization and colocalization analyses
- Author
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Shuai-Kang Wang, Qi-Jun Wang, Xuan Zhao, Peng Wang, Xiang-Yu Li, Wei Wang, and Shi-Bao Lu
- Subjects
Muscle weakness ,Hand grip strength ,Protein ,Mendelian randomization ,Therapeutic target ,Internal medicine ,RC31-1245 - Abstract
Background: Recent research highlights the importance of muscular strength as a key factor in physical fitness, a strong indicator of overall mortality risk, and a vital target for preventing chronic diseases. This study used a proteome-wide Mendelian randomization analysis plus colocalization analysis for low hand grip strength to explore potential therapeutic targets for muscle weakness. Methods: We conducted two two-sample Mendelian randomization analyses from four cohorts to identify and validate the causal relationship between plasma proteins and low grip strength. We also employed bidirectional Mendelian randomization analysis with Steiger filtering, Bayesian co-localization, and phenotype scanning to detect reverse causality, thereby consolidating our Mendelian randomization findings. Downstream analyses were also undertaken of identified proteins, including knockout models, enrichment analyses, and protein-protein interaction networks. Finally, we assessed the druggability of the identified proteins. Results: At Bonferroni significance (P
- Published
- 2024
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