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Editors Selection IGR 11-1

Epidemiology: Interplay of alcohol consumption and genetics in predisposition for glaucoma

Comment by Victoria L. Tseng & Anne Coleman on:

106598 The Association of Alcohol Consumption with Glaucoma and Related Traits: Findings from the UK Biobank, Stuart KV; Luben RN; Warwick AN et al., Ophthalmology. Glaucoma, 2023; 6: 366-379

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This observational study examined the association between alcohol consumption, glaucoma, and glaucoma-related traits in the UK Biobank. The authors utilized a glaucoma polygenic risk score (PRS) to examine genetic modification of these associations, and employ Mendelian randomization (MR) to assess for causality. Alcohol consumption was estimated based on questionnaire responses regarding frequency, portion size, and type of alcohol consumed. Glaucoma was assessed by self-report and administrative codes. Glaucoma-related traits included intraocular pressure (IOP) and thickness of macular retinal nerve fiber layer (mRNFL) and macular ganglion cell-inner plexiform layer (mGCIPL) on optical coherence tomography (OCT). Associations between alcohol consumption and glaucoma and its related traits were calculated using linear and logistic regression modeling, adjusting for several demographic, systemic, and socioeconomic covariates. For genetic analyses, associations between alcohol and glaucoma were calculated in glaucoma PRS quintiles. For MR analyses, an instrumental variable approach was employed using genetic variants associated with alcohol intake.

There were 81,324, 36,143, and 84,655 participants with IOP, OCT, and glaucoma diagnosis data available, respectively. Compared to infrequent drinkers, regular drinkers had higher IOP (0.17 mmHg, 95% confidence interval [CI] 0.10 to 0.24 mmHg) and thinner mGCIPL (-0.17 µm, 95% CI -0.33 to 0.00 µm). In regular drinkers, each additional 111-112 g of alcohol intake was associated with higher IOP (0.08 mmHg, 95% CI 0.05 to 0.11 mmHg), thinner mRNFL (-0.17 µm, 95% CI -0.22 to -0.12 µm), thinner mGCIPL (-0.34 µm, 95% CI -0.40 to -0.27 µm), and higher glaucoma prevalence (odds ratio 1.11, 95% CI 1.05-1.18). The glaucoma PRS was found to significantly modify the association between alcohol and IOP, with stronger associations between alcohol intake and high IOP in participants with the highest quintile of genetic risk. There was suggestion of a causal association between alcohol intake and mGCIPL thickness in MR analyses.

Study results suggest likely associations between increased alcohol intake and higher IOP, thinner mRNFL, and thinner mGCIPL

The assessment of alcohol intake as a risk factor is challenging due to multiple potential sources of bias in observational studies and ethical issues in randomizing subjects to alcohol use or not in a prospective study. The authors are to be commended for their use of rigorous statistical approaches and a comprehensive dataset to examine associations between alcohol and glaucoma, and to explore the role of genetics in these associations. The inclusion of a large number and variety of covariates accounts for several possible sources of confounding. Consistency of results with multiple types of sensitivity analyses decreases the likelihood that significant associations are spurious. The use of MR is a unique method to assess for potential causality that capitalizes on the abundant information available in the UK Biobank. Study results suggest likely associations between increased alcohol intake and higher IOP, thinner mRNFL, and thinner mGCIPL. Further studies are needed to assess whether the amount of change detected in these parameters with increased alcohol intake translate to a clinically significant difference in glaucoma risk and visual function, and whether interventions on alcohol intake could modulate these differences.

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