Blood pressure may raise eye pressure, Canadian genetic study suggests

Higher blood pressure appears to go hand in hand with higher pressure inside the eye, and for the first time a study has used both individual-level and summary-level genetic data to ask whether that link could be causal. Analyzing more than 21,000 middle-aged and older Canadian adults, researchers found that systolic blood pressure, diastolic blood pressure, and pulse pressure were each positively associated with intraocular pressure, the fluid pressure within the eye. Genetic analyses then offered some support for the idea that higher systolic blood pressure may itself drive eye pressure upward, although the evidence was not uniform across all methods used.

The study, published in Frontiers in Genetics, drew on baseline data from the Canadian Longitudinal Study on Aging (CLSA), a cohort of community-dwelling adults aged 45 to 85 recruited from seven provinces between 2010 and 2015. After restricting the sample to non-closely related participants of European descent with complete blood pressure and eye pressure measurements, 21,633 individuals remained eligible for the individual-level analyses. Eye pressure was measured with an ocular response analyzer, and the average corneal-compensated value from both eyes was used. Blood pressure was measured six times with an automated monitor, with the first reading discarded and the remaining five averaged.

In multivariable linear regression models adjusted for age, sex, province, marital status, education, income, diabetes, smoking, alcohol intake, body mass index, and serum lipids, every 10 mmHg increase in systolic blood pressure was associated with roughly a 0.22 mmHg increase in intraocular pressure. Diastolic pressure showed an even steeper slope, about 0.37 mmHg per 10 mmHg, and pulse pressure about 0.20 mmHg per 10 mmHg. All three associations were statistically strong, with P values at or below 3.82 × 10−17. These estimates are comparable to those from an earlier meta-analysis, which reported that eye pressure rises on average by 0.26 mmHg per 10 mmHg of systolic pressure.

A central question was whether genetic susceptibility to elevated eye pressure changes how blood pressure relates to eye pressure. To test this, the team constructed a polygenic risk score from 122 genetic variants independently associated with intraocular pressure in a prior genome-wide association study of 139,555 Europeans. Interaction analyses found no evidence that the score modified the blood pressure–eye pressure relationships, with interaction P values of at least 0.122 across models. In other words, the observational association appeared consistent regardless of a participant’s inherited predisposition toward higher eye pressure.

To probe causality, the researchers turned to Mendelian randomization, a technique that uses genetic variants as instruments to estimate whether an exposure has a causal effect on an outcome, thereby limiting the confounding and reverse causation that can distort ordinary observational studies. Because blood pressure variants were drawn from the largest available genome-wide association meta-analysis, involving up to roughly one million individuals of European descent, and CLSA participants were independent of both the blood pressure and eye pressure discovery samples, concerns about participant overlap were minimized.

The one-sample Mendelian randomization analysis, performed within the CLSA itself using two-stage least squares regression, found that genetically predicted systolic blood pressure was positively associated with eye pressure, with an estimated increase of 0.227 mmHg in eye pressure per 10 mmHg increase in systolic pressure (95% confidence interval 0.074 to 0.381, P = 0.004). Genetically predicted diastolic pressure and pulse pressure showed no significant associations. Reverse analyses testing whether eye pressure causally influences blood pressure found no support for that direction, with P values of at least 0.103. Results were similar after excluding participants taking eye pressure–lowering or antihypertensive medications, and after fuller covariate adjustment.

Two-sample Mendelian randomization, which combined the blood pressure variant effects from the external meta-analysis with variant–eye pressure associations estimated within the CLSA, also pointed toward a positive causal effect of systolic pressure. The inverse-variance weighted random-effects estimate was 0.216 mmHg of eye pressure per 10 mmHg of systolic pressure, with the contamination mixture and MR-PRESSO methods yielding estimates of 0.314 and 0.239 mmHg respectively, all statistically significant. However, the MR-Egger intercept test flagged evidence of directional pleiotropy for the systolic instruments (P = 0.049), a warning that some variants may influence eye pressure through pathways other than blood pressure, which could bias the estimate. When participants taking eye pressure–lowering medications were excluded from the CLSA-based estimates, the positive systolic findings held and the pleiotropy signal was no longer significant (P = 0.062).

The picture was not entirely consistent. When the analyses were repeated with Steiger filtering, a procedure that removes variants explaining more variation in the outcome than in the exposure, the two-sample results retained nominal support through the contamination mixture method, but the one-sample systolic finding did not survive. The authors also noted that their study may have been underpowered for some comparisons: with 80% power, the one-sample analysis could only detect effects of at least 0.219, 0.358, and 0.329 mmHg per 10 mmHg for systolic, diastolic, and pulse pressure respectively, thresholds above some of the point estimates reported. Restricting the cohort to participants of European descent, done to limit population stratification bias, also limits how broadly the findings generalize.

The broader context complicates any simple interpretation. Elevated intraocular pressure is the only known modifiable risk factor for glaucoma, an often asymptomatic disease projected to affect 111.8 million people aged 40 to 80 by 2040, and lowering eye pressure is currently the only effective way to slow its progression. Yet the relationship between blood pressure and glaucoma itself appears U-shaped, with evidence that both low and high blood pressure are associated with increased disease risk, possibly because high systemic pressure can reduce blood flow to the optic nerve through effects on ocular perfusion. A causal effect of blood pressure on eye pressure, if real, would fit the hypothesis that higher systemic pressure increases aqueous humor production at the ciliary body or reduces its outflow by raising episcleral venous pressure, mechanisms that may depend more on systolic than diastolic pressure.

The authors conclude that systolic, diastolic, and pulse pressures are positively associated with intraocular pressure, that genetic susceptibility to elevated eye pressure does not appear to modify these associations, and that Mendelian randomization provides some evidence of a potential causal effect of systolic pressure on eye pressure. If future work confirms causality, they suggest, ophthalmologists treating elevated eye pressure might encourage patients to keep their blood pressure under control as well. For now, the findings remain a carefully qualified step toward understanding how a systemic cardiovascular trait could shape the pressure environment inside the eye.

Subject of Research: The association and potential causal effect of blood pressure on intraocular pressure in the Canadian Longitudinal Study on Aging

Article Title: Blood pressure and intraocular pressure in the Canadian Longitudinal Study on Aging: a bidirectional Mendelian randomization analysis

Article References: Bastasic, J., Rakesh, M., Freeman, E. E., Little, J., Burkett, K. M., & Roy-Gagnon, M.-H. (2026). Blood pressure and intraocular pressure in the Canadian Longitudinal Study on Aging: a bidirectional Mendelian randomization analysis. Frontiers in Genetics, 17, Article 1967280. https://doi.org/10.3389/fgene.2026.1967280

Image Credits: AI Generated

DOI: 10.3389/fgene.2026.1967280

Keywords: blood pressure, intraocular pressure, glaucoma, Mendelian randomization, Canadian Longitudinal Study on Aging, polygenic risk score, systolic blood pressure, pulse pressure, genetic epidemiology, pleiotropy, ophthalmology, cross-sectional study