Oxidative stress and neurodegenerative diseases: a bidirectional Mendelian randomization study

Area of Science:

• Neuroscience
• Genetics
• Epidemiology

Background:

• Oxidative stress (OS) is implicated in neurodegenerative diseases, but its causal role is debated.
• Distinguishing between OS as a cause or consequence is crucial for understanding disease mechanisms.

Purpose of the Study:

• To investigate the causal relationship between 15 oxidative stress markers and three major neurodegenerative diseases.
• To assess genetic evidence for causality using a bidirectional Mendelian randomization approach.

Main Methods:

• A two-sample bidirectional Mendelian randomization (MR) analysis was performed.
• Inverse-variance weighted (IVW), weighted-median (WM), and Radial MR methods were employed.
• Sensitivity and pleiotropy analyses ensured robustness of findings.

Main Results:

• Nominal causal correlations were observed between zinc and Parkinson's disease risk, alpha-tocopherol and ALS risk, and Alzheimer's disease and uric acid.
• These associations did not meet statistical significance after Bonferroni correction.

Conclusions:

• No statistically significant genetic causal associations were identified between oxidative stress biomarkers and the studied neurodegenerative diseases.
• The complex interplay between oxidative stress and neurodegeneration requires further experimental investigation.