eprintid: 10161667 rev_number: 12 eprint_status: archive userid: 699 dir: disk0/10/16/16/67 datestamp: 2022-12-14 14:49:15 lastmod: 2024-10-17 15:33:23 status_changed: 2022-12-14 14:49:15 type: article metadata_visibility: show sword_depositor: 699 creators_name: Stuart, Kelsey V creators_name: Luben, Robert N creators_name: Warwick, Alasdair N creators_name: Madjedi, Kian M creators_name: Patel, Praveen J creators_name: Biradar, Mahantesh I creators_name: Sun, Zihan creators_name: Chia, Mark A creators_name: Pasquale, Louis R creators_name: Wiggs, Janey L creators_name: Kang, Jae H creators_name: Kim, Jihye creators_name: Aschard, Hugues creators_name: Tran, Jessica H creators_name: Lentjes, Marleen AH creators_name: Foster, Paul J creators_name: Khawaja, Anthony P creators_name: Modifiable Risk Factors for Glaucoma Collaboration, the UK Biobank Eye and Vision Consortium creators_name: the International Glaucoma Genetics Consortium, . title: The association of alcohol consumption with glaucoma and related traits: findings from the UK Biobank ispublished: inpress subjects: MOOR divisions: UCL divisions: B02 divisions: C07 divisions: D08 keywords: Alcohol, UK Biobank, glaucoma, intraocular pressure, optical coherence tomography note: Copyright 2022 by the American Academy of Ophthalmology. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). abstract: 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 two-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 (RCS) regression, adjusted for key sociodemographic, medical, anthropometric and lifestyle factors, were used to examine associations. We assessed whether any association was modified by a multi-trait glaucoma polygenic risk score. The inverse-variance weighted method was used for the main MR analyses. MAIN OUTCOME MEASURES: IOP, macular retinal nerve fiber layer (mRNFL) thickness, macular ganglion cell-inner plexiform layer (mGCIPL) thickness, and prevalent glaucoma. RESULTS: Compared to infrequent drinkers, regular drinkers had higher IOP (+0.17mmHg; P<0.001) and thinner mGCIPL (-0.17μm; P=0.049); while former drinkers had a higher prevalence of glaucoma (OR 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). RCS regression analyses suggested non-linear associations, with apparent threshold effects at approximately 50g (∼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). MR 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 UK (<112g/week) and US (women: <98g/week; men: <196g/week) guidelines. While we cannot infer causality definitively, these results will be of interest to people with, or at risk of, glaucoma and their advising physicians. date: 2022-12-05 date_type: published publisher: Elsevier BV official_url: https://doi.org/10.1016/j.ogla.2022.11.008 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 1994699 doi: 10.1016/j.ogla.2022.11.008 medium: Print-Electronic pii: S2589-4196(22)00235-6 lyricists_name: Khawaja, Anthony lyricists_name: Stuart, Kelsey lyricists_name: Sun, Zihan lyricists_id: APKHA37 lyricists_id: KVSTU50 lyricists_id: ZSUNC67 actors_name: Kalinowski, Damian actors_id: DKALI47 actors_role: owner full_text_status: public publication: Ophthalmol Glaucoma event_location: United States citation: Stuart, Kelsey V; Luben, Robert N; Warwick, Alasdair N; Madjedi, Kian M; Patel, Praveen J; Biradar, Mahantesh I; Sun, Zihan; ... the International Glaucoma Genetics Consortium, .; + view all <#> Stuart, Kelsey V; Luben, Robert N; Warwick, Alasdair N; Madjedi, Kian M; Patel, Praveen J; Biradar, Mahantesh I; Sun, Zihan; Chia, Mark A; Pasquale, Louis R; Wiggs, Janey L; Kang, Jae H; Kim, Jihye; Aschard, Hugues; Tran, Jessica H; Lentjes, Marleen AH; Foster, Paul J; Khawaja, Anthony P; Modifiable Risk Factors for Glaucoma Collaboration, the UK Biobank Eye and Vision Consortium; the International Glaucoma Genetics Consortium, .; - view fewer <#> (2022) The association of alcohol consumption with glaucoma and related traits: findings from the UK Biobank. Ophthalmol Glaucoma 10.1016/j.ogla.2022.11.008 <https://doi.org/10.1016/j.ogla.2022.11.008>. (In press). Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10161667/1/1-s2.0-S2589419622002356-main.pdf