Frontiers in Aging Neuroscience · 6 authors, 4 centres
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A bidirectional two-sample Mendelian randomization study used GWAS summary data to assess causal relationships between 41 circulating inflammatory cytokines and glaucoma, cataract, and macular degeneration. Six cytokines were identified as potentially causally associated with these diseases by inverse variance weighted analysis, though none remained significant after Bonferroni correction, and reverse MR suggested cataract may lead to decreased VEGF levels.
This study employed bidirectional two-sample Mendelian randomization using publicly available GWAS summary statistics to investigate causal relationships between 41 circulating inflammatory cytokines and three blinding eye diseases: glaucoma, cataract, and macular degeneration. The inverse variance weighted method served as the primary analytical approach, supplemented by MR-Egger regression, weighted median, weighted mode, Cochran's Q test, MR-PRESSO, and leave-one-out tests. Forward MR identified MIG as associated with glaucoma risk, IL-1ra, IL-6, IL-10, and PDGFbb with cataract, and MIG and HGF with macular degeneration risk. However, none of these associations survived Bonferroni correction (p < 0.0004). Reverse MR indicated cataract may decrease VEGF levels. The study is limited by reliance on summary-level GWAS data, potential pleiotropy despite sensitivity analyses, and the observational nature of the underlying genetic instruments, warranting validation through animal and population-based studies.
