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Association of myopia and intraocular pressure with retinal detachment in European descent participants of the UK Biobank cohort: a mendelian randomization study

Han, X, Ong, J-S, An, J, Craig, JE, Gharahkhani, P, Hewitt, AW ORCID: 0000-0002-5123-5999 and Macgregor, S 2020 , 'Association of myopia and intraocular pressure with retinal detachment in European descent participants of the UK Biobank cohort: a mendelian randomization study' , JAMA Ophthalmology, no. April , E1-E8 , doi: 10.1001/jamaophthalmol.2020.1231.

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Abstract

Importance: Rhegmatogenous retinal detachment is a potentially sight-threatening condition. The role of myopia or intraocular pressure (IOP) in retinal detachment remains unclear.Objective: To determine if myopia or IOP is associated with retinal detachment risk using genetic data.Design, setting, and participants: Observational analyses and 2-sample mendelian randomization were used to evaluate the associations between myopia, IOP, and retinal detachment risk in European descent participants from the UK Biobank (UKBB) cohort (n = 405 692). For retinal detachment, a genome-wide association study on 4257 cases and 39 181 controls in the UKBB was conducted. Genetic variants associated with mean spherical equivalent (MSE) refractive error (n = 95 827) and IOP (n = 101 939) were derived using independent participants from the retinal detachment genome-wide association study. Recruitment to the UKBB occurred between 2006 and 2010, and data analysis occurred from February 2019 to March 2020. Main outcomes and measures: The odds ratio (OR) of retinal detachment caused by per-unit increases in MSE refractive error (in diopters [D]) and IOP (in mm Hg). Results: Of the 405 692 participants in the UKBB cohort, the mean (SD) age was 56.87 (7.96) years, the mean (SD) MSE was -0.31 (2.65) D, the mean (SD) corneal-compensated IOP was 16.05 (3.49) mm Hg, and 4253 participants (1.0%) had retinal detachment. Genetic analyses of the 4257 cases and 39 181 controls identified 2 novel retinal detachment genes: COL22A1 (lead single-nucleotide variant rs11992725; P = 4.8 × 10-10) and FAT3 (lead single-nucleotide variant rs10765568; P = 1.2 × 10-15). Genetically assessed MSE refractive error was negatively associated with retinal detachment (per-unit [D] increase in MSE refractive error: OR, 0.72; 95% CI, 0.69-0.76; P = 3.8 × 10-44). For each 6-D decrease in MSE refractive error (representing the move of refractive error from emmetropia to high myopia), retinal detachment risk increased 7.2-fold (95% CI, 5.19-9.27). For per-unit (mm Hg) genetically assessed increase in IOP, the risk of retinal detachment increased by 8% (OR, 1.08; 95% CI, 1.03-1.14; P = .001). Conclusions and relevance: This study provides genetic support for the assertion that myopia and IOP are associated with the risk of retinal detachment and that myopia prevention efforts may help prevent retinal detachment.

Item Type: Article
Authors/Creators:Han, X and Ong, J-S and An, J and Craig, JE and Gharahkhani, P and Hewitt, AW and Macgregor, S
Journal or Publication Title: JAMA Ophthalmology
Publisher: American Medical Association
ISSN: 2168-6165
DOI / ID Number: 10.1001/jamaophthalmol.2020.1231
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© 2020 American Medical Association. All rights reserved.

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