Causal associations between cognitive impairments and retinal diseases: A two-sample Mendelian randomization study

Area of Science:

• Neuroscience
• Ophthalmology
• Genetics

Background:

• Dementia and retinal diseases share risk factors and potential biological mechanisms.
• Investigating causal links is crucial for understanding disease pathogenesis and developing interventions.

Purpose of the Study:

• To explore bidirectional causal relationships between Alzheimer's disease, Lewy body dementia, vascular dementia, and various retinal diseases using Mendelian randomization.
• To identify shared genetic underpinnings and potential therapeutic targets.

Main Methods:

• Employed a bidirectional two-sample Mendelian randomization approach.
• Utilized summary data from large-scale genome-wide association studies (GWAS) of European ancestry.
• Applied inverse variance-weighted, Mendelian randomization-Egger, weighted median, and weighted mode analyses for robust causal inference.

Main Results:

• Alzheimer's disease showed reduced risk for choroid/retina disorders and retinal detachments.
• Lewy body dementia and vascular dementia were associated with reduced risk of age-related macular degeneration and macular degeneration.
• Reverse analysis indicated genetic liability to macular degeneration and retinal disorders causally linked to cognitive performance and reduced Alzheimer's risk.

Conclusions:

• Evidence supports inverse causal relationships between specific dementias and retinal diseases.
• Shared biological mechanisms likely underlie these complex associations.
• Findings may inform future research into integrated treatment strategies.