Habitual Coffee Consumption Increases Risk of Primary Open-Angle Glaucoma

Purpose: To explore whether there is a causal relationship between coffee consumption and primary open-angle glaucoma (POAG). Design: Two-sample Mendelian randomization (MR). Participants: The single-nucleotide polymorphisms (SNPs) associated with coffee consumption (including phenotypes 1 and 2) were selected from a genome-wide association study (GWAS) involving 121 824 individuals of European descent. Coffee intake from the MRC-IEU UK Biobank was also used to identify instruments for coffee intake. Summary-level data for POAG were obtained from the largest publicly available meta-analyses involving 16 677 POAG cases and 199 580 controls of European descent. Methods: The inverse variance-weighted (IVW) method was the main MR analysis, whereas weighted-median, weighted mode-based estimate (MBE), MR Pleiotropy RESidual Sum and Outlier (PRESSO) test, and MR-Egger regression were used for sensitivity analysis. Main Outcome Measures: Diagnosis of POAG. Results: Three sets of instrumental variables were used to evaluate the causal association between coffee consumption and POAG risk. Results showed that genetically predicted higher coffee consumption phenotype 1 (cups/day) was significantly associated with higher risk of POAG (odds ratio [OR], 1.241; 95% confidence interval [CI], 1.041-1.480; P = 0.016). Genetically predicted higher coffee consumption phenotype 2 (high vs. no/low) was also significantly associated with higher risk of POAG (OR, 1.155; 95% CI, 1.038-1.284; P = 0.008, using the IVW method). Moreover, genetically predicted higher coffee intake from the MRC-IEU UK Biobank OpenGWAS was significantly associated with a higher risk of POAG (OR, 1.727; 95% CI, 1.230-2.425; P = 0.002, using the IVW method). Sensitivity analyses confirmed that the findings were robust to possible pleiotropy. Conclusions: These findings provide the genetic evidence that higher coffee consumption is associated with a higher risk of POAG. Given that coffee is widely consumed, our findings provide new insights into potential strategies to prevent and manage POAG. (c) 2022 by the American Academy of Ophthalmology

Automated summary

This study explored the causal relationship between coffee consumption and primary open-angle glaucoma (POAG) using two-sample Mendelian randomization (MR). The results showed that genetically predicted higher coffee consumption was significantly associated with a higher risk of POAG, providing new insights into the prevention and management of POAG.