Mendelian Randomization Study of Age-Related Macular Degeneration and Inflammatory Bowel Disease

To investigate the causal relationship between age-related macular degeneration (AMD) and inflammatory bowel disease (IBD) by Mendelian randomization (MR) analysis. The single nucleotide polymorphism data of IBD and AMD were obtained from the Integrative Epidemiology Unit (IEU) Open genome-wide association study database. MR analysis contained MR-Egger, weighted median, inverse variance weighted, simple mode, and weighted mode. Sensitivity analysis was executed to ensure the reliability of results, containing heterogeneity test, horizontal pleiotropy test, and leave-one-out analysis. Multivariable Mendelian randomization analysis was carried out to investigate potential confounding factors such as C-reactive protein, smoking, vitamin D deficiency. Genes corresponding to the instrumental variables (IVs) and functional enrichment analysis were executed. MR analysis showed a positive correlation between IBD and AMD (P 1). Sensitivity analyses also did not reveal heterogeneity and horizontal pleiotropy. C-reactive protein, smoking, and vitamin D deficiency had no significant effect on AMD (P > 0.05). Genes corresponding to IVs were mainly associated with monocyte differentiation, cytokine receptor activity, etc., and act on signaling pathways such as Th17 cell differentiation, and there was a complex network of molecular-cell regulation. Our study explored and demonstrated the causal relationship between IBD and AMD through MR analysis, which provided an important reference and direction for future research and treatment related to AMD.