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Genetically low vitamin D concentrations and myopic refractive error: a Mendelian randomization study

Citation

Cuellar-Partida, G and Williams, KM and Yazar, S and Guggenheim, JA and Hewitt, AW and Williams, C and Wang, JJ and Kho, P-F and Saw, SM and Cheng, C-Y and Wong, TY and Aung, T and Young, TL and Tideman, JWL and Jonas, JB and Mitchell, P and Wojciechowski, R and Stambolian, D and Hysi, P and Hammond, CJ and Mackey, DA and Lucas, RM and MacGregor, S, Consortium for Refractive Error and Myopia (CREAM), Genetically low vitamin D concentrations and myopic refractive error: a Mendelian randomization study, International Journal of Epidemiology, 46, (6) pp. 1882-1890. ISSN 0300-5771 (2017) [Refereed Article]

Copyright Statement

Copyright The Author 2017; all rights reserved.

DOI: doi:10.1093/ije/dyx068

Abstract

Background: Myopia prevalence has increased in the past 20 years, with many studies linking the increase to reduced time spent outdoors. A number of recent observational studies have shown an inverse association between vitamin D [25(OH)D] serum levels and myopia. However, in such studies it is difficult to separate the effects of time outdoors and vitamin D levels. In this work we use Mendelian randomization (MR) to assess if genetically determined 25(OH)D levels contribute to the degree of myopia.

Methods: We performed MR using results from a meta-analysis of refractive error (RE) genome-wide association study (GWAS) that included 37 382 and 8 376 adult participants of European and Asian ancestry, respectively, published by the Consortium for Refractive Error And Myopia (CREAM). We used single nucleotide polymorphisms (SNPs) in the DHCR7 , CYP2R1, GC and CYP24A1 genes with known effects on 25(OH)D concentration as instrumental variables (IV). We estimated the effect of 25(OH)D on myopia level using a Wald-type ratio estimator based on the effect estimates from the CREAM GWAS.

Results: Using the combined effect attributed to the four SNPs, the estimate for the effect of 25(OH)D on refractive error was -0.02 [95% confidence interval (CI) -0.09, 0.04] dioptres (D) per 10 nmol/l increase in 25(OH)D concentration in Caucasians and 0.01 (95% CI -0.17, 0.19) D per 10 nmol/l increase in Asians.

Conclusions: The tight confidence intervals on our estimates suggest the true contribution of vitamin D levels to degree of myopia is very small and indistinguishable from zero. Previous findings from observational studies linking vitamin D levels to myopia were likely attributable to the effects of confounding by time spent outdoors.

Item Details

Item Type:Refereed Article
Keywords:Mendelian randomization, myopia, vitamin D
Research Division:Medical and Health Sciences
Research Group:Ophthalmology and Optometry
Research Field:Ophthalmology
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Hearing, Vision, Speech and Their Disorders
Author:Hewitt, AW (Professor Alex Hewitt)
Author:Mackey, DA (Professor David Mackey)
ID Code:117402
Year Published:2017
Web of Science® Times Cited:1
Deposited By:Menzies Institute for Medical Research
Deposited On:2017-06-13
Last Modified:2018-06-04
Downloads:0

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