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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.
Original language | English |
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Pages (from-to) | 1882–1890 |
Number of pages | 9 |
Journal | International Journal of Epidemiology |
Volume | 46 |
Issue number | 6 |
DOIs | |
Publication status | Published - 1 Dec 2017 |
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Dive into the research topics of 'Genetically low vitamin D concentrations and myopic refractive error: a Mendelian randomization study'. Together they form a unique fingerprint.Projects
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Genes for juvenile-onset myopia
Mackey, D. (Investigator 01), Pennell, C. (Investigator 02), Hewitt, A. (Investigator 03), Young, T. (Investigator 04), Hammond, C. (Investigator 05), Coroneo, M. (Investigator 06) & MacGregor, S. (Investigator 07)
NHMRC National Health and Medical Research Council
1/01/12 → 31/12/14
Project: Research