The Associations Between Cataracts and Alzheimer’s Disease: A Bidirectional Two-Sample Mendelian Randomization Study

Background: The relationship between cataracts and Alzheimer’s disease (AD) has been reported in recent observational studies. However, it is still unclear whether a causal effect of cataracts on AD or reverse causation exists. Objective: To explore the association between cataracts and AD genetically, we performed a bidirectional two-sample Mendelian randomization study. Methods: We obtained genetic instrumental variables related to cataracts and AD from recently published genome-wide association studies (GWASs). SNP-outcome associations for AD were obtained from a GWAS with 111,326 cases and 677,663 controls. SNP-outcome associations for cataracts were drawn from two sources: a GWAS with 67,844 cases and 517,399 controls and the FinnGen consortium (42,843 cases and 262,698 controls). Inverse variance weighted (IVW) was used as the primary method for Mendelian randomization (MR) analyses. Results: No genetic evidence suggested that cataracts were associated with the risk of AD (IVW odds ratio =1.04, 95% confidence interval: 0.98-1.10, p=0.199). In contrast, an effect of genetically determined AD on a decreased risk of cataract was observed with suggestive evidence (IVW odds ratio =0.96, 95% confidence interval: 0.93-0.99, p=0.004). However, this result might be distorted by survival bias. Conclusion: Genetically determined cataracts were not related to AD, as demonstrated by our study. In contrast, there was suggestive evidence that AD might prevent cataract development, but there might be potential survival bias. To define the exact association between the two diseases, more prospective research and studies on the pathogenesis are needed.