Biomedicines
Genetically Predicted Circulating Lipid Traits and Risk of Primary Open-Angle Glaucoma: A Mendelian Randomization Study
By Ahmed El Ashry, Marwa El-Ashry, Hajirah N. Saeed and 1 others.
Abstract
Background
Observational studies examining the relationship between serum lipids and primary open-angle glaucoma (POAG) have yielded inconsistent findings, limiting causal inference. Mendelian randomization (MR) offers a robust approach to evaluate causality by leveraging genetic variants as proxies for modifiable exposures, thereby minimizing confounding and reverse causation.
Methods
A two-sample MR study was conducted using GWAS summary statistics for 179 circulating lipid traits (GCST90277238–GCST90277416) as exposures and POAG cases from the FinnGen consortium (Release R12, endpoint H7_GLAUCOMA_POAG) as the outcome. Genetic variants were selected as instrumental variables at p < 1 × 10−5 and clumped for linkage disequilibrium (R2 < 0.001). The inverse variance weighted (IVW) method was the primary analysis. Multiple testing was addressed using both Bonferroni and false discovery rate (FDR) correction. Instrument strength was assessed via F-statistics for all 179 traits. Sensitivity analyses included MR-Egger regression, weighted median, weighted mode, MR-PRESSO, Cochran’s Q, and leave-one-out analysis.
