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Telomere Length and Parkinson’s Disease Traits: A Mendelian Randomization Study

DOI: 10.4236/apd.2025.142002, PP. 13-37

Keywords: Parkinson’s Disease, Telomere Length, Aging, Mendelian Randomization

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Abstract:

Parkinson’s disease (PD) is a neurodegenerative condition influenced by aging, but the biological pathways linking age to PD remain unclear. Telomere length (TL), a marker of cellular aging, has been inconsistently linked to PD in observational studies. To assess potential causal relationships, we conducted two-sample Mendelian randomization (MR), a genetic approach that uses naturally occurring genetic variation to study causality. We used genetic instruments from a large genome-wide association study of TL (472,147 participants) and tested their associations with PD-related traits: disease risk, age at onset, binary motor subtype (tremor-dominant vs. postural instability/gait difficulty), and a continuous motor subtype score. We also assessed reverse causality to test whether PD traits may causally influence TL, using instruments derived from genome-wide association studies for each outcome. No causal relationships were detected in either direction (all p > 0.05). These findings suggest that leukocyte TL is not a causal factor for PD risk or related clinical traits. Future research should investigate TL in brain-specific tissues and explore other aging biomarkers in relation to PD.

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