TY - JOUR
T1 - The Association of Alcohol Consumption with Glaucoma and Related Traits
T2 - Findings from the UK Biobank
AU - Members of the International Glaucoma Genetics Consortium
AU - Modifiable Risk Factors for Glaucoma Collaboration, the UK Biobank Eye and Vision Consortium, and the International Glaucoma Genetics Consortium
AU - Members of the Modifiable Risk Factors for Glaucoma Collaboration
AU - Members of the UK Biobank Eye and Vision Consortium
AU - Stuart, Kelsey V.
AU - Luben, Robert N.
AU - Warwick, Alasdair N.
AU - Madjedi, Kian M.
AU - Patel, Praveen J.
AU - Biradar, Mahantesh I.
AU - Sun, Zihan
AU - Chia, Mark A.
AU - Pasquale, Louis R.
AU - Wiggs, Janey L.
AU - Kang, Jae H.
AU - Kim, Jihye
AU - Aschard, Hugues
AU - Tran, Jessica H.
AU - Lentjes, Marleen A.H.
AU - Foster, Paul J.
AU - Khawaja, Anthony P.
AU - Chia, Mark
AU - Chua, Sharon
AU - Do, Ron
AU - Foster, Paul
AU - Kang, Jae
AU - Kastner, Alan
AU - Khawaja, Anthony
AU - Lentjes, Marleen
AU - Luben, Robert
AU - Madjedi, Kian
AU - Montesano, Giovanni
AU - Pasquale, Louis
AU - Warwick, Alasdair
AU - Wiggs, Janey
AU - Allen, Naomi
AU - Aslam, Tariq
AU - Atan, Denize
AU - Barman, Sarah
AU - Barrett, Jenny
AU - Bishop, Paul
AU - Black, Graeme
AU - Braithwaite, Tasanee
AU - Carare, Roxana
AU - Chakravarthy, Usha
AU - Chan, Michelle
AU - Day, Alexander
AU - Desai, Parul
AU - Dhillon, Bal
AU - Dick, Andrew
AU - Doney, Alexander
AU - Egan, Cathy
AU - Ennis, Sarah
AU - Wojciechowski, Robert
N1 - Publisher Copyright:
© 2022 American Academy of Ophthalmology
PY - 2023/7/1
Y1 - 2023/7/1
N2 - Purpose: To examine the associations of alcohol consumption with glaucoma and related traits, to assess whether a genetic predisposition to glaucoma modified these associations, and to perform Mendelian randomization (MR) experiments to probe causal effects. Design: Cross-sectional observational and gene–environment interaction analyses in the UK Biobank. Two-sample MR experiments using summary statistics from large genetic consortia. Participants: UK Biobank participants with data on intraocular pressure (IOP) (n = 109 097), OCT-derived macular inner retinal layer thickness measures (n = 46 236) and glaucoma status (n = 173 407). Methods: Participants were categorized according to self-reported drinking behaviors. Quantitative estimates of alcohol intake were derived from touchscreen questionnaires and food composition tables. We performed a 2-step analysis, first comparing categories of alcohol consumption (never, infrequent, regular, and former drinkers) before assessing for a dose-response effect in regular drinkers only. Multivariable linear, logistic, and restricted cubic spline regression, adjusted for key sociodemographic, medical, anthropometric, and lifestyle factors, were used to examine associations. We assessed whether any association was modified by a multitrait glaucoma polygenic risk score. The inverse-variance weighted method was used for the main MR analyses. Main Outcome Measures: Intraocular pressure, macular retinal nerve fiber layer (mRNFL) thickness, macular ganglion cell–inner plexiform layer (mGCIPL) thickness, and prevalent glaucoma. Results: Compared with infrequent drinkers, regular drinkers had higher IOP (+0.17 mmHg; P < 0.001) and thinner mGCIPL (-0.17 μm; P = 0.049), whereas former drinkers had a higher prevalence of glaucoma (odds ratio, 1.53; P = 0.002). In regular drinkers, alcohol intake was adversely associated with all outcomes in a dose-dependent manner (all P < 0.001). Restricted cubic spline regression analyses suggested nonlinear associations, with apparent threshold effects at approximately 50 g (∼6 UK or 4 US alcoholic units)/week for mRNFL and mGCIPL thickness. Significantly stronger alcohol–IOP associations were observed in participants at higher genetic susceptibility to glaucoma (Pinteraction < 0.001). Mendelian randomization analyses provided evidence for a causal association with mGCIPL thickness. Conclusions: Alcohol intake was consistently and adversely associated with glaucoma and related traits, and at levels below current United Kingdom (< 112 g/week) and United States (women, < 98 g/week; men, < 196 g/week) guidelines. Although we cannot infer causality definitively, these results will be of interest to people with or at risk of glaucoma and their advising physicians. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.
AB - Purpose: To examine the associations of alcohol consumption with glaucoma and related traits, to assess whether a genetic predisposition to glaucoma modified these associations, and to perform Mendelian randomization (MR) experiments to probe causal effects. Design: Cross-sectional observational and gene–environment interaction analyses in the UK Biobank. Two-sample MR experiments using summary statistics from large genetic consortia. Participants: UK Biobank participants with data on intraocular pressure (IOP) (n = 109 097), OCT-derived macular inner retinal layer thickness measures (n = 46 236) and glaucoma status (n = 173 407). Methods: Participants were categorized according to self-reported drinking behaviors. Quantitative estimates of alcohol intake were derived from touchscreen questionnaires and food composition tables. We performed a 2-step analysis, first comparing categories of alcohol consumption (never, infrequent, regular, and former drinkers) before assessing for a dose-response effect in regular drinkers only. Multivariable linear, logistic, and restricted cubic spline regression, adjusted for key sociodemographic, medical, anthropometric, and lifestyle factors, were used to examine associations. We assessed whether any association was modified by a multitrait glaucoma polygenic risk score. The inverse-variance weighted method was used for the main MR analyses. Main Outcome Measures: Intraocular pressure, macular retinal nerve fiber layer (mRNFL) thickness, macular ganglion cell–inner plexiform layer (mGCIPL) thickness, and prevalent glaucoma. Results: Compared with infrequent drinkers, regular drinkers had higher IOP (+0.17 mmHg; P < 0.001) and thinner mGCIPL (-0.17 μm; P = 0.049), whereas former drinkers had a higher prevalence of glaucoma (odds ratio, 1.53; P = 0.002). In regular drinkers, alcohol intake was adversely associated with all outcomes in a dose-dependent manner (all P < 0.001). Restricted cubic spline regression analyses suggested nonlinear associations, with apparent threshold effects at approximately 50 g (∼6 UK or 4 US alcoholic units)/week for mRNFL and mGCIPL thickness. Significantly stronger alcohol–IOP associations were observed in participants at higher genetic susceptibility to glaucoma (Pinteraction < 0.001). Mendelian randomization analyses provided evidence for a causal association with mGCIPL thickness. Conclusions: Alcohol intake was consistently and adversely associated with glaucoma and related traits, and at levels below current United Kingdom (< 112 g/week) and United States (women, < 98 g/week; men, < 196 g/week) guidelines. Although we cannot infer causality definitively, these results will be of interest to people with or at risk of glaucoma and their advising physicians. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.
KW - Alcohol
KW - Glaucoma
KW - Intraocular pressure
KW - OCT
KW - UK Biobank
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U2 - 10.1016/j.ogla.2022.11.008
DO - 10.1016/j.ogla.2022.11.008
M3 - Article
C2 - 36481453
AN - SCOPUS:85146634254
SN - 2589-4234
VL - 6
SP - 366
EP - 379
JO - Ophthalmology Glaucoma
JF - Ophthalmology Glaucoma
IS - 4
ER -