Mendelian randomization in eye disorders (review)

Abstract

Background: Mendelian randomization (MR) is an analytic approach in genetic epidemiology which uses the results of genome-wide association studies (GWAS) to assess causal relationships between various risk factors and phenotypes of interest (or diseases) in ophthalmology. The aim of the study: To describe the current opportunities for the use of MR in ophthalmic research. Materials and methods: We searched Scopus, Medline and Web of Science journals up to August 2022 using the PRISMA protocol “Preferred Reporting Items for Systematic Review and Meta-Analysis”. The following information was extracted: identified risk factor(s) and disease(s), design of Mendelian randomization study, sensitivity analysis(es) performed if any, genetic instrument(s) used, and also whether the causal relationship between risk and outcome was confirmed by the results of the study. Results: The current review included a total of 37 publications that tested 211 associations of a risk factor with an ophthalmic disease. The articles included were published in peer-reviewed journals up to August 2022 with 25 of them (67,5%) published in 2020 or later. The MR method indicated the causal role of blood serum lipids, C-reactive protein, free thyroxine, smoking and alcohol intake in the development of age-related macular degeneration. For glaucoma, type 2 diabetes, serum glucose, refractive abnormalities, and elevated intraocular pressure have been shown to be significant. MR analysis revealed the role of elevated intraocular pressure, level of education, body weight at birth in the development of refractive errors. The role of type 2 diabetes, hypertension and smoking in the development of cataracts was determined using the MR method. Conclusion: The results of 97 MR analyses in ophthalmology have revealed a significant role of a number of risk factors in the development of eye diseases, which will serve as a guideline for clinical trials and drug development.