Objective: To examine causal associations between sarcopenia-related traits and the risk or progression of Parkinson’s disease (PD) using a Mendelian randomization (MR) approach.

Background: Previous observational studies suggested that sarcopenia is associated with PD, but it is unclear whether this association is causal.

Method: Two-sample bidirectional MR analyses were conducted to evaluate causal relationships. Genome-wide association study (GWAS) summary statistics for sarcopenia-related traits, including right handgrip strength (n=461,089), left handgrip strength (n= 461,026), and appendicular lean mass (n=450,243), were retrieved from the IEU OpenGWAS database. GWAS data for the risk of PD were derived from the FinnGen database (4,235 cases; 373,042 controls). Summary-level data for progression of PD, including progression to Hoehn and Yahr stage 3, progression to dementia, and development of levodopa-induced dyskinesia, were obtained from a recent GWAS publication on progression of PD in 4093 patients from 12 longitudinal cohorts. Significant causal associations identified in MR analysis were verified through a polygenic score (PGS)-based approach using genotype data from the Parkinson’s Progression Markers Initiative.

Results: MR results supported a significant causal influence of right handgrip strength (odds ratio [OR]=0.152, 95% confidence interval [CI]=0.055–0.423, P=0.0036) and appendicular lean mass (OR=0.597, 95% CI=0.440–0.810, P=0.011) on development of levodopa-induced dyskinesia. In Cox proportional hazard analysis, higher PGSs for right handgrip strength (hazard ratio [HR]=0.225, 95% CI=0.095–0.530, P=0.0019) and left handgrip strength (HR=0.303, 95% CI=0.121–0.59, P=0.0323) were significantly associated with a lower risk of developing levodopa-induced dyskinesia, after adjusting for covariates.

Conclusion: This study provides genetic evidence of the protective role of handgrip strength or appendicular lean mass on the development of levodopa-induced dyskinesia in PD. Sarcopenia-related traits can be promising prognostic markers for levodopa-induced dyskinesia and potential therapeutic targets for preventing levodopa-induced dyskinesia in patients with PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/causal-effects-of-sarcopenia-related-traits-on-risk-and-progression-of-parkinsons-disease-a-mendelian-randomization-study/