Bidirectional Causal Relationship Between Myopia and Neurodegenerative Diseases: Two-Sample Mendelian Randomization...

Area of Science:

• Ophthalmology
• Neuroscience
• Genetics

Background:

• Myopia (nearsightedness) and neurodegenerative diseases (NDDs) share genetic links.
• Prevalence of myopia is notable in some NDDs, prompting investigation into potential connections.

Purpose of the Study:

• To investigate bidirectional causal relationships between myopia and four NDDs: Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS).
• To determine if myopia increases NDD risk or if NDDs increase myopia risk.

Main Methods:

• Utilized Mendelian randomization (MR) with large-scale genome-wide association study (GWAS) data for myopia (212,571 and 95,619 participants) and four NDDs (589,439 samples).
• Employed inverse variance-weighted (IVW) as the primary method, with sensitivity analyses (MR-Egger, weighted median, etc.) to ensure robustness.
• Assessed pleiotropy and heterogeneity using MR-Egger intercept, MR-PRESSO, and Cochran's Q tests.

Main Results:

• No evidence of a causal relationship was found between myopia and an increased risk of any of the four NDDs.
• Conversely, no significant association was observed where NDDs increased the risk of myopia or refractive error.
• Sensitivity analyses confirmed the robustness of these findings, with no single nucleotide polymorphisms (SNPs) significantly influencing the results.

Conclusions:

• This MR study found no evidence of a bidirectional causal link between myopia and Parkinson's disease, Alzheimer's disease, multiple sclerosis, or amyotrophic lateral sclerosis in European ancestry populations.
• Future research should explore potential mediating biological mechanisms beyond direct causal inference.