Tea Intake Increases Risk of Glaucoma: A Multivariable Mendelian Randomization Study

Abstract Background Numerous observational studies reported that tea intake decreases the risk of glaucoma. However, the observed correlation is inconclusive. To investigate the causal relationship between genetically predicted tea intake and glaucoma, ocular hypertension (OHT), primary angle-open glaucoma (POAG), and intraocular pressure (IOP), we performed a two-sample Mendelian randomization (MR) study based on GWAS summary data. Methods Genetic instruments for tea intake were obtained from UK Biobank involving 447,485 people. Summary-level data on outcomes were retrieved from the FinnGen project comprising 377,277 individuals (including 18,902 of glaucoma, 10,758 of OHT, and 7,756 POAG participants). Data for confounder factors (smoking, coffee consumption, and alcohol drinking) and intermediary factors (intraocular pressure) came from different GWAS meta-analysis studies. We explored the causal effect of tea intake and glaucoma outcomes by conducting two-sample MR, multivariable MR, and two-step MR. Inverse variance-weighted (IVW) analysis was used as the primary method for causal analysis. Additionally, a sensitivity analysis was conducted to ensure the reliability of the results. Results Two-sample MR found that genetically predicted tea intake was causally associated with a higher risk of glaucoma [IVW odds ratio, OR IVW = 1.41, 95% confidence interval (CI) = 1.09–1.84, P = 0.009], as well as ocular hypertension [OR IVW = 1.40, 95% CI = 1.07–1.83, P = 0.013]. Multivariate MR indicated that the adverse causality effect remained significant, even after adjustment for other modifiable factors. Mediation analysis via two-step MR showed that these effects were not mediated by intraocular pressure, suggesting an independent causal mechanism between tea intake and a higher risk of glaucoma and ocular hypertension. Sensitivity analyses found little evidence of pleiotropy. Conclusions Genetically predicted tea intake has a causal effect on the increased risk of glaucoma and ocular hypertension. Moreover, this harmful causal association is not mediated by intraocular pressure.