Genetic evidence for a causal relationship between Alzheimer’s disease and age-related macular degeneration: A Mendelian randomization study

Abstract

Abstract Background Previous observational studies have established a bi-directional association between age-related macular degeneration (AMD) and Alzheimer’s disease (AD). However, these associations might be induced by confounding factors. Methods We conducted a bi-directional MR study to evaluate potential causal associations between AMD and AD using GWAS data. 39,106 clinically diagnosed AD cases, 46,828 proxy AD and related dementia, and 14,034 AMD patients were included in this study. Results Increased AMD exposure due to germline genetic variation was generally associated with decreased risk for AD. A causal effect was observed between early AMD and AD. However, reverse–direction MR analysis depicted generally little evidence of an association between genetically increased AD exposure and risk of early AMD with 57 SNPs and risk of AMD progression. Conclusions Our MR study confirmed the causal effect of early AMD on AD, and early AMD could reduce the risk for AD.