Refractive error and Alzheimer's disease: A bidirectional Mendelian randomization study

Abstract Background and aims: Observational studies have shown an association between refractive error and Alzheimer's disease (AD). However, whether there is a causal relationship between them remains unclear. This study aimed to investigate the association between genetically predicted refractive error and Alzheimer's disease and vice versa. Methods A bidirectional Mendelian randomization (MR) study of refractive error and Alzheimer's disease from European ancestry was performed using summary statistics from Genome-Wide Association Studies. A series of sensitivity studies, such as heterogeneity tests, multiple validity tests, and leave one out analyses, were also conducted to further assess the accuracy of the MR analyses. Results In the forward MR analysis, no significant association was found between refractive error and Alzheimer's disease using 98 genome-wide single nucleotide polymorphisms (SNPs) as instrumental variables for refractive error (IVW: β = 0.003, 95%CI of 0.931 to 1.080, P = 0.936). However, in the reverse MR analysis, three genome-wide SNPs were used as instrumental variables for Alzheimer's disease, revealing a significant association between Alzheimer's disease and refractive error (IVW༚β = 4.616, 95%CI of 5.447 to 1876.674, P = 0.001). Moreover, the weighted median analysis yielded consistent results. Conclusions Our research findings suggest that refractive errors seem to be unrelated to Alzheimer's disease. Conversely, refractive errors may be downstream effects of Alzheimer's disease.