A study published in Ophthalmology with participants of mostly European ancestry found that genetically predicted higher coffee consumption had a direct causal relationship with a higher risk of being diagnosed with primary open-angle glaucoma (POAG) using 2-sample Mendelian randomization (MR).
The study authors used a previous meta-analysis of genome-wide association studies (GWASs) from the Coffee and Caffeine Genetics Consortium, which involved 121,824 participants of European descent, to select single nucleotide polymorphisms (SNPs) associated with coffee consumption.
There were 6 SNPs that were selected for phenotype 1, which was the genetic association that estimates cups of regular coffee consumed per day (cups/day) among coffee consumers. Phenotype 2 had 3 SNPs selected to compare high consumers of coffee with infrequent consumers or nonconsumers (high vs no/low).
Statistics from MRC-IEU UK Biobank OpenGWAS were used for data on coffee intake, which included 428,860 European participants. Summary-level data for POAG were obtained from meta-analyses that involved 16,677 POAG cases and 199,850 controls. “A total of 35 independent SNPs were identified as genetic instruments for UK Biobank coffee intake,” the authors wrote.
The results of the study identified genetically predicted higher coffee consumption as significantly associated with higher risk of POAG (odds ratio [OR], 1.241; 95% CI, 1.041-1.480) in phenotype 1, with a correct causal direction confirmed with the Steiger directionality test.
Genetically predicted higher coffee consumption was also significantly associated with higher risk of POAG (OR, 1.155; 95% CI, 1.038-1.284) in participants with phenotype 2. Risk estimates were consistent when using weighted median (OR, 1.148; 95% CI, 1.035-1.273) and weighted mode-based estimate (OR, 1.136; 95% CI, 1.002-1.289) approaches. The causal relationship was confirmed using the MR-Steiger directionality test.
In the analysis of UK Biobank coffee intake as it relates to POAG risk, genetically predicted higher coffee intake was significantly associated with higher risk of POAG (OR, 1.727; 95% CI, 1.230-2.425). Again, a causal relationship was also found using the MR-Steiger directionality test.
There were some limitations to this study. The study was restricted to participants of European ancestry, which makes generalizability difficult. There is a possibility that variants used in the MR have a risk of POAG through a pleiotropic pathway, although there was no evidence of pleiotropy that were observed. Data on coffee consumption traits were collected via interviewer or questionnaire in previous studies, so the exact chemical composition of different coffee preparations may not have been captured. The critical dosage and precise effect of coffee consumption on development of POAG could not be quantified in this study.
The researchers concluded that their findings “provide the genetic evidence that high 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,” the authors wrote.
Li X, Cheng S, Cheng J, Wang M, Zhong Y, Yu AY. Habitual coffee consumption increases risk of primary open-angle glaucoma: a mendelian randomization study. Ophthalmology. Published online May 7, 2022. doi:10.1016/j.ophtha.2022.04.027