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Abstract #127477 Published in IGR 25-3
Unraveling the link: Is Parkinson's disease a causal factor for glaucoma? Insights from Mendelian randomization
Bin Lin MM; Long-Long Chen MM; Mei-Yi Zhu MM; Dong-Kan Li MDScience progress 2025; 108: 368504251377961
BACKGROUND: Glaucoma is recognized as the second-leading cause of complete blindness in developed countries and a significant contributor to irreversible vision loss worldwide. Understanding the potential genetic links between neurodegenerative diseases, such as Parkinson's disease, and glaucoma is crucial for developing preventive strategies. METHODS: This study utilized data from Genome-Wide Association Studies databases, focusing on European populations without gender restrictions. Single nucleotide polymorphisms (SNPs) were selected as instrumental variables based on criteria ensuring no direct association with outcomes and independence from confounding factors. Mendelian randomization analyses were conducted to assess the relationship between SNP effect sizes for Parkinson's disease and the risk of developing glaucoma. Finally, detailed information on high-risk SNP loci was queried and compared in the Ensembl gene database to further explore the relationship between the two diseases. RESULTS: The analysis revealed that for every one standard deviation increase in the SNP effect size for Parkinson's disease, the risk of developing glaucoma increased by 0.3% to 11.9%. Pleiotropy testing indicated a -value of 0.464, suggesting that genetic pleiotropy is unlikely to affect the results. Sensitivity analyses confirmed the stability of the findings. A notable observation is the proximity between the loci of both diseases on chromosome 7. However, this positional overlap alone, without functional validation, does not confirm biological relevance. CONCLUSION: The study provides suggestive evidence of a potential causal relationship, suggesting that genetic factors associated with Parkinson's disease may potentially contribute to an increased risk of glaucoma. These findings tentatively highlight the need to consider neurodegeneration-related mechanisms in glaucoma management and prevention, though further validation is required.
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