Cannabis use and the risk of primary open-angle glaucoma: a Mendelian randomization study

Abstract

Several observational studies have investigated the association between cannabis use and intraocular pressure, but its association with primary open-angle glaucoma (POAG) remains unclear. In this study, we leveraged human genetic data to assess through Mendelian randomization (MR) whether cannabis use affects POAG. We used five single-nucleotide polymorphisms (SNPs) associated with lifetime cannabis use (P-value < 5 × 10^-8) from a genome-wide association study (GWAS) (N = 184,765) by the International Cannabis Consortium, 23andMe, and UK Biobank and eleven SNPs associated with cannabis use disorder (P-value < 5 × 10^-7) from a GWAS meta-analysis of (17,068 cases and 357,219 controls of European descent) from Psychiatric Genomics Consortium Substance Use Disorders working group, Lundbeck Foundation Initiative for Integrative Psychiatric Research, and deCode. We associated the selected five SNPs from the GWAS of lifetime cannabis use and the eleven SNPs from the GWAS of cannabis use disorder, with the largest to date GWAS meta-analysis of POAG (16,677 cases and 199,580 controls). MR analysis suggested no evidence for a causal association of lifetime cannabis use and cannabis use disorder with POAG (odds ratio (OR) of outcome per doubling of the odds of exposure (95% confidence interval): 1.04 (0.88; 1.23) for lifetime cannabis use and 0.97 (0.92; 1.03) for cannabis use disorder). Sensitivity analyses to address pleiotropy and weak instrument bias yielded similar estimates to the primary analysis. In conclusion, our results do not support a causal association between cannabis use and POAG.

Figure 1

Mendelian randomization estimates for the effect of lifetime cannabis use on primary open-angle glaucoma. Estimates are reported as changes in odds of primary open-angle glaucoma per doubling in the prevalence of lifetime cannabis use^a. ^aSNP single nucleotide polymorphism; CI confidence interval; MR-PRESSO Mendelian randomization pleiotropy residual sum and outlier; CAUSE causal analysis using summary effect estimates; BMI body mass index.

Figure 2

Mendelian randomization estimates for the effect of cannabis use disorder on primary open-angle glaucoma. Estimates are reported as changes in odds of primary open-angle glaucoma per doubling in the prevalence of cannabis use disorder^a. ^aSNP single nucleotide polymorphism; CI confidence interval; MR-PRESSO Mendelian randomization pleiotropy residual sum and outlier; CAUSE causal analysis using summary effect estimates; BMI body mass index.