Mendelian randomization study updates the effect of hypertension on the risk of primary open-angle glaucoma

Abstract Objectives: To investigate the causal association between hypertension and primary open-angle glaucoma (POAG). Methods: The hypertension-associated genome-wide association study (GWAS) was from UK biobank (UKB), involving 463010 participants. The GWAS of POAG is obtained from FinnGene project involving 4433 cases and 210201 controls. All participants were of European ancestry. The inverse-variance weighted (IVW) method was used as the primary analysis method to estimate the causality of hypertension on POAG. Meanwhile, MR Egger, weighted median, Weighted Median estimation, calculation of Cochran Q statistics, MR-Egger intercept test, MR-PRESSO global test and leave-one-out analysis were performed to verify the efficiency and consistency of the results. Results: A total of 57 hypertension related single-nucleotide polymorphisms (SNPs) were strongly associated with POAG after excluding potential confounders (old age, diabetes, myopia) and harmonizing the variants. IVW results showed that the incidence of POAG in patients with hypertension was 5.372 times higher than that in the control group (OR: 6.372, 95% CI: 1.824-22.262, P = 0.004). The results of Weighted median (OR: 9.707, P = 0.017), Maximum likelihood (OR: 6.642, P = 0.003), Penalised weighted median (OR: 9.696, P = 0.013) verified the casual association between hypertension and POAG. And the results of heterogeneity analysis, egger intercept and MR-PRESSO global test further confirmed the reliability of the findings. Conclusions: A causal association was suggested between genetically increased hypertension and higher risk of POAG. Long-term cohort studies are expected to verify the impact of hypertension on POAG.