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

Gabriel Cuellar-Partida, Katie M Williams, Seyhan Yazar, Jeremy A Guggenheim, Alex W Hewitt, Cathy Williams, Jie Jin Wang, Pik-Fang Kho, Seang Mei Saw, Ching-Yu Cheng, Tien Yin Wong, Tin Aung, Terri L Young, J Willem L Tideman, Jost B Jonas, Paul Mitchell, Robert Wojciechowski, Dwight Stambolian, Pirro Hysi, Christopher J HammondDavid A Mackey, Robyn M Lucas, Stuart MacGregor, Consortium for Refractive Error and Myopia (CREAM)

Research output: Contribution to journalArticle (Academic Journal)peer-review

27 Citations (Scopus)
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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 languageEnglish
Article numberdyx068
Pages (from-to)1882–1890
Number of pages9
JournalInternational Journal of Epidemiology
Volume46
Issue number6
Early online date6 Jun 2017
DOIs
Publication statusPublished - Dec 2017

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