Abstract
Purpose: To test for causality with regard to the association between blood pressure (BP) and intraocular pressure (IOP) and glaucoma.
Methods: Single nucleotide polymorphisms (SNPs) associated with BP were identified in a genome-wide association study (GWAS) meta-analysis of 526,001 participants of European ancestry. These SNPs were used to assess the BP versus IOP relationship in a distinct sample (n = 70,832) whose corneal-compensated IOP (IOPcc) was measured. To evaluate the BP versus primary open-angle glaucoma (POAG) relationship, additional Mendelian randomization (MR) analyses were conducted using published GWAS summary statistics.
Results: Observational analysis revealed a linear relationship between BP traits and IOPcc, with a +0.28 mm Hg increase in IOPcc per 10-mm Hg increase in systolic BP (95% confidence interval [CI], 0.26-0.29); for diastolic blood pressure (DBP) and pulse pressure (PP), these estimates were +0.41 mm Hg and +0.36 mm Hg, respectively. An inverse-variance weighted MR analysis did not support a causal relationship, as the estimated causal effect was +0.01 mm Hg IOPcc per 10-mm Hg increase in systolic blood pressure (SBP); +0.13 mm Hg IOPcc per 10-mm Hg increase in DBP; and +0.02 mm Hg IOPcc per 10-mm Hg increase in PP (all P > 0.05). With regard to the risk of POAG, MR analyse yielded causal effect estimate of odds ratio = 0.98 (95% CI, 0.92-1.04) per 10-mm Hg increase in SBP. Neither DBP nor PP demonstrated evidence of a causal effect on POAG.
Conclusions: A range of different MR analysis methods provided evidence, in general, that the causal effect of BP on IOP (and POAG) was modest, or even zero. However, interpretation was complicated by SNPs associated with BP potentially having pleiotropic effects on IOP.