Mendelian randomization study of causality between 35 blood and urine biomarkers and age-related eye diseases

Age-related eye diseases (AREDs) are a group of age-related visual degenerative diseases characterized by insidious and gradual onset. Identification of biomarkers associated with the early stage of AREDs is particularly important to delay its progression. This study aimed to evaluate the causal relationship between 35 blood and urine biomarkers and AREDs, thereby providing new insights into disease mechanisms and potential therapeutic targets. Two-sample Mendelian randomization (MR) was used to clarify the causal relationship between blood and urine biomarkers and AREDs. We classified AREDs into 4 types: age-related cataract (SC), age-related macular degeneration, glaucoma, and diabetic retinopathy. Inverse variance weighting method was used as the main analysis method, Cochran Q test, MR-Egger intercept, and leave-one-out test were used to investigate whether there was heterogeneity and pleiotropy of MR results. And the results were corrected by false discovery rate. Through MR analysis, this study provides the first systematic genetic evidence regarding the associations between blood and urine biomarkers and 4 AREDs. Specifically, our findings suggest a causal effect of 1 biomarker on SC, support causal roles of 3 biomarkers in age-related macular degeneration, and indicate causal relationships for 3 biomarkers with diabetic retinopathy. The reliability of these results was bolstered by a series of sensitivity analyses. This study strengthened the link between specific blood and urine biomarkers and the risk of AREDs. It has enhanced our understanding of the pathogenesis of AREDs and may guide the development of targeted prevention, diagnosis, and treatment strategies.