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Causal associations between cognitive impairments and retinal diseases: A two-sample Mendelian randomization study
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Causal associations between cognitive impairments and retinal diseases: A two-sample Mendelian randomization study
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Journal Article
Causal associations between cognitive impairments and retinal diseases: A two-sample Mendelian randomization study
2025
Overview
Objective
This study employed a bidirectional two-sample Mendelian randomization approach to investigate the causal links between Alzheimer’s disease, Lewy body dementia, vascular dementia, and various retinal diseases.
Methods
Summary data from large-scale genome-wide association studies of European ancestry were used to select genetic variants as instrumental variables. Causal estimates were derived using the inverse variance–weighted method, complemented by Mendelian randomization–Egger, weighted median, and weighted mode analyses to ensure robustness.
Results
Genetically predicted Alzheimer’s disease was associated with a reduced risk of disorders of the choroid and retina (odds ratio = 0.93, 95% confidence interval: 0.88–0.98), retinal detachments and breaks (odds ratio = 0.90, 95% confidence interval: 0.84–0.97), and retinal detachment with retinal break (odds ratio = 0.84, 95% confidence interval: 0.74–0.95). Lewy body dementia was negatively associated with age-related macular degeneration (odds ratio = 0.88, 95% confidence interval: 0.79–0.98), disorders of the choroid and retina (odds ratio = 0.96, 95% confidence interval: 0.93–0.99), and degeneration of the macula (odds ratio = 0.93, 95% confidence interval: 0.88–0.98). Vascular dementia showed negative associations with age-related macular degeneration (odds ratio = 0.93, 95% confidence interval: 0.87–0.99) and degeneration of the macula (odds ratio = 0.96, 95% confidence interval: 0.93–0.99). Conversely, reverse Mendelian randomization indicated that genetic liability to macular degeneration and choroidal/retinal disorders was causally associated with cognitive performance and a reduced risk of Alzheimer’s disease.
Conclusions
Findings support inverse causal relationships in which specific dementias may reduce retinal disease risk and vice versa, suggesting complex shared biological mechanisms.
Publisher
SAGE Publications,Sage Publications Ltd,SAGE Publishing
Subject
/ Cognitive Dysfunction - genetics
/ Dementia
/ Dementia, Vascular - genetics
/ Disease
/ Genetic Predisposition to Disease
/ Genome-Wide Association Study
/ Humans
/ Lewy Body Disease - genetics
/ Macular Degeneration - genetics
/ Mendelian Randomization Analysis
/ Polymorphism, Single Nucleotide
