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

Cuellar-Partida, G, Williams, KM, Yazar, S, Guggenheim, JA, Hewitt, AW ORCID: 0000-0002-5123-5999, Williams, C, Wang, JJ, Kho, PF, Saw, SM, Cheng, CY, Wong, TY, Aung, T, Young, TL, Tideman, JWL, Jonas, JB, Mitchell, P, Wojciechowski, R, Stambolian, D, Hysi, P, Hammond, CJ, Mackey, DA, Lucas, RM and MacGregor, S 2017 , 'Genetically low vitamin D concentrations and myopic refractive error: a Mendelian randomization study' , International Journal of Epidemiology, vol. 46, no. 6 , pp. 1882-1890 , doi: 10.1093/ije/dyx068.

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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 Type: Article
Authors/Creators:Cuellar-Partida, G and Williams, KM and Yazar, S and Guggenheim, JA and Hewitt, AW and Williams, C and Wang, JJ and Kho, PF and Saw, SM and Cheng, CY 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
Keywords: Mendelian randomization, myopia, vitamin D
Journal or Publication Title: International Journal of Epidemiology
Publisher: Oxford Univ Press
ISSN: 0300-5771
DOI / ID Number: 10.1093/ije/dyx068
Copyright Information:

Copyright The Author 2017; all rights reserved.

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