To explore whether there is a causal relationship between coffee consumption and primary open-angle glaucoma (POAG).
Two-sample Mendelian randomization.
The single-nucleotide polymorphisms (SNPs) associated with coffee consumption (including phenotype 1 and phenotype 2) were selected from a genome-wide association study (GWAS) involving 121,824 individuals of European descent. Coffee intake from 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.
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.
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% 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 MRC-IEU UK Biobank OpenGWAS was significantly associated with 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.
In conclusion, 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.