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Refractive error has minimal influence on the risk of age-related macular degeneration: A Mendelian randomization study

Wood, Ashley and Guggenheim, Jeremy 2019. Refractive error has minimal influence on the risk of age-related macular degeneration: A Mendelian randomization study. American Journal of Ophthalmology 206 , pp. 87-93. 10.1016/j.ajo.2019.03.018
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Abstract

Purpose To test the hypothesis that refractive errors such as myopia and hyperopia cause an increased risk of age-related macular degeneration (AMD), and to quantify the degree of risk. Design Two-sample Mendelian randomization analysis of data from a genome-wide association study Participants As instrumental variables for refractive error, 126 genome-wide significant genetic; variants identified by the CREAM consortium and 23andMe Inc. were chosen. The association with refractive error for the 126 variants was obtained from a published study for a sample of n=95,505 European ancestry participants from UK Biobank. Association with AMD for the 126; genetic variants was determined from a genome-wide association study (GWAS) published by; the International Age-related Macular Degeneration Genomics consortium of n=33,526 (16,144; cases and 17,832 controls) European ancestry participants. Methods Two-sample Mendelian randomization analysis was used to assess the causal role of refractive error on AMD risk, using the 126 genetic variants associated with refractive error as; instrumental variables, under the assumption that the relationship between refractive error and; AMD risk is linear. Main Outcome Measures The risk AMD caused by a 1 diopter (D) change in refractive error. Results Mendelian randomization analysis suggested that refractive error had very limited influence on the risk of AMD. Specifically, a 1 D more hyperopic refractive error was associated with an OR=1.080 (95% CI: 1.021 to 1.142, P=0.007) increased risk of AMD. MR-Egger, MR-PRESSO, weighted median, and Phenoscanner-based sensitivity analyses detected minimal evidence to suggest that this result was biased by horizontal pleiotropy. Conclusions Under the assumption of a linear relationship between refractive error and the risk of AMD, myopia and hyperopia only minimally influence the causal risk for AMD. Thus, inconsistently-reported strong associations between refractive error and AMD are likely to be; the result of non-causal factors, such as stochastic variation, confounding or selection bias.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Optometry and Vision Sciences
Publisher: Elsevier Masson
ISSN: 0002-9394
Date of First Compliant Deposit: 5 April 2019
Date of Acceptance: 11 March 2019
Last Modified: 20 Oct 2019 12:34
URI: http://orca.cf.ac.uk/id/eprint/121525

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