Causal associations between sarcopenia and Parkinson's disease ‒ A two-sample Mendelian randomization study

Area of Science:

• Neurology
• Genetics
• Gerontology

Background:

• Sarcopenia, the loss of muscle mass and function, is prevalent in Parkinson's disease (PD).
• The causal relationship between sarcopenia and PD risk remains unclear.

Purpose of the Study:

• To investigate the potential causal associations between sarcopenia-related traits and Parkinson's disease (PD) risk.
• Utilizing a two-sample Mendelian randomization (MR) approach.

Main Methods:

• Extracted genome-wide association study (GWAS) data for PD and sarcopenia traits (handgrip strength, appendicular lean mass, walking pace).
• Performed MR analyses using inverse-variance-weighted, MR-Egger, weighted-median, and weighted-mode methods.
• Conducted sensitivity analyses to assess for horizontal pleiotropy.

Main Results:

• Genetically predicted low handgrip strength was significantly associated with a reduced risk of PD (IVW OR = 0.66, p = 0.01).
• No significant causal associations were found between appendicular lean mass or usual walking pace and PD risk.
• Sensitivity analyses indicated that the results were robust and not significantly affected by horizontal pleiotropy.

Conclusions:

• Low muscle strength, a component of sarcopenia, may have a protective causal effect against Parkinson's disease (PD) development.
• Appendicular lean mass and walking pace do not appear to have a significant causal relationship with PD risk.
• Further research is warranted to elucidate the underlying mechanisms connecting muscle strength and PD pathogenesis.