Genetic Correlation and Mendelian Randomization Analyses Support Causal Relationships Between Instant Coffee and Age-Related Macular Degeneration

Abstract

Coffee is a popular beverage, and previous cohort studies suggest it may reduce the risk of age-related macular degeneration (AMD). However, confounding factors in these studies necessitate further exploration of causal relationships using advanced methods. We obtained data on coffee consumption from genome-wide association studies (GWAS) and the latest AMD-related GWAS summary data from the Finngen consortium R11. We assessed their genetic correlation using linkage disequilibrium score regression (LDSC), explored causal associations using Mendelian randomization (MR), and identified shared genetic loci via colocalization. Our results revealed a genetic correlation between instant coffee consumption and dry AMD, with each standard deviation (SD) increase in instant coffee intake associated with a corresponding odds ratio (OR) of approximately 6.92 for dry AMD, indicating a 6.92-fold increased risk. However, colocalization analysis did not show shared genetic variants between instant coffee consumption and AMD. Instant coffee may increase the risk of AMD, and reducing its intake could help prevent dry AMD. People at high-risk for AMD should avoid instant coffee. This study aids clinicians in identifying dietary factors, particularly instant coffee consumption, as potential risks for AMD. By providing genetically based causal evidence, our findings support the development of personalized AMD prevention strategies. Clinicians can advise patients to reduce instant coffee intake based on genetic risk profiles, offering a precision approach to reduce dry AMD risk. These interventions may significantly contribute to AMD prevention and treatment.