Development of targeted drugs for diabetic retinopathy using Mendelian randomized pharmacogenomics

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Purpose This study aims to utilize genetic instrumental variables - protein quantitative trait loci (pQTL), and through analysis methods such as Mendelian randomization (MR), systematically screen and validate druggable proteins that have a causal relationship with diabetic retinopathy (DR), and further explore related drug targets, providing genetic evidence and new directions for the drug development of this disease. Methods The research was based on large-scale public databases to conduct two-sample Mendelian randomization (MR) analysis. Firstly, 511 encoded proteins were selected from the known 4,479 druggable genes as initial exposure factors, with the summary data of GWAS for diabetic retinopathy as the outcome. MR analysis was conducted using the inverse variance weighted (IVW) method and the Wald ratio method, and strict screening was performed through Bonferroni correction. For the significantly associated proteins, heterogeneity tests, pleiotropy tests, leave-one-out analysis, and Steiger directionality tests were further conducted to verify the robustness of the results. Additionally, summary MR (SMR) analysis and colocalization analysis (coloc) were used to confirm the reliability of the causal relationship. Finally, a protein-protein interaction (PPI) network was constructed using the STRING database, and potential targeted drugs were mined from the DrugBank and DS

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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