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Editors Selection IGR 9-4

Risk Factors: Is Coffee a Risk Factor in Glaucoma?

Comment by Louis Pasquale & Kelsey Stuart on:

100555 Habitual Coffee Consumption Increases Risk of Primary Open-Angle Glaucoma: A Mendelian Randomization Study, Li X; Cheng S; Cheng S; Cheng J et al., Ophthalmology, 2022; 129: 1014-1021

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Mendelian randomization (MR) offers a complementary approach to epidemiology studies, substituting common genetic variants as instrumental variables (IVs) for exposures. The technique is analogous to a natural randomized controlled trial and, provided certain assumptions are met, allows for causal inferences from observational data.¹

Li and colleagues employ a two-sample MR approach to evaluate whether there is a link between coffee consumption and primary open-angle glaucoma (POAG). Using various IVs from the latest genome-wide association study of glaucoma, they show that genetically predicted coffee consumption is adversely associated with POAG risk.² Sensitivity analyses, using alternative MR methods, suggest these findings are robust, and they find no evidence for secondary genetic associations with traditional glaucoma risk factors, including intraocular pressure (IOP).

This is the first study using an MR approach to assess the relationship between coffee consumption and glaucoma risk. Recently, a large population-based study found that caffeine consumption was adversely associated with glaucoma, but only in participants with the strongest genetic predisposition to elevated IOP.³39-73 years The same study found no evidence for a causal role of coffee consumption on IOP in a MR analysis, findings that support the current study.

Despite the robust results, it is possible that the genetic variants used confer a risk of POAG through pleiotropic pathways

In MR studies, causal inferences are only possible when the IV assumptions are satisfied.¹ Despite the robust results, it is possible that the genetic variants used confer a risk of POAG through pleiotropic pathways (a violation of the exclusion restriction assumption). This is a particular possibility when using a statistically-driven approach to IV selection for complex traits, as the biological implications of the utilized genetic variants are not well understood. For example, a coffee consumption IV may be more reflective of an underlying genetic propensity to addiction, implicating alternative pathways unrelated to caffeine intake.

Further research is needed before dietary recommendations can be made to individuals with, or at risk of, glaucoma.

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