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 G. Hysi, Christopher J. Hammond & 4 others David A Mackey, Robyn M Lucas, Stuart MacGregor, Consortium for Refractive Error and Myopia (CREAM)

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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
Pages (from-to)1882–1890
JournalInternational Journal of Epidemiology
Volume46
Issue number6
DOIs
Publication statusPublished - 1 Dec 2017

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Refractive Errors
Myopia
Random Allocation
Vitamin D
Genome-Wide Association Study
Confidence Intervals
Observational Studies
Single Nucleotide Polymorphism
Meta-Analysis
Serum

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Cuellar-Partida, G., Williams, K. M., Yazar, S., Guggenheim, J. A., Hewitt, A. W., Williams, C., ... Consortium for Refractive Error and Myopia (CREAM) (2017). Genetically low vitamin D concentrations and myopic refractive error: a Mendelian randomization study. International Journal of Epidemiology, 46(6), 1882–1890. https://doi.org/10.1093/ije/dyx068
Cuellar-Partida, Gabriel ; Williams, Katie M ; Yazar, Seyhan ; Guggenheim, Jeremy A ; Hewitt, Alex W ; Williams, Cathy ; Wang, Jie Jin ; Kho, Pik-Fang ; Saw, Seang Mei ; Cheng, Ching Yu ; Wong, Tien Yin ; Aung, Tin ; Young, Terri L ; Tideman, J Willem L ; Jonas, Jost B. ; Mitchell, Paul ; Wojciechowski, Robert ; Stambolian, Dwight ; Hysi, Pirro G. ; Hammond, Christopher J. ; Mackey, David A ; Lucas, Robyn M ; MacGregor, Stuart ; Consortium for Refractive Error and Myopia (CREAM). / Genetically low vitamin D concentrations and myopic refractive error : a Mendelian randomization study. In: International Journal of Epidemiology. 2017 ; Vol. 46, No. 6. pp. 1882–1890.
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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.",
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Cuellar-Partida, G, Williams, KM, Yazar, S, Guggenheim, JA, Hewitt, AW, Williams, C, Wang, JJ, Kho, P-F, Saw, SM, Cheng, CY, Wong, TY, Aung, T, Young, TL, Tideman, JWL, Jonas, JB, Mitchell, P, Wojciechowski, R, Stambolian, D, Hysi, PG, Hammond, CJ, Mackey, DA, Lucas, RM, MacGregor, S & Consortium for Refractive Error and Myopia (CREAM) 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. https://doi.org/10.1093/ije/dyx068

Genetically low vitamin D concentrations and myopic refractive error : a Mendelian randomization study. / Cuellar-Partida, Gabriel; Williams, Katie M; Yazar, Seyhan; Guggenheim, Jeremy A; Hewitt, Alex W; Williams, Cathy; Wang, Jie Jin; Kho, Pik-Fang; Saw, Seang Mei; Cheng, Ching Yu; Wong, Tien Yin; Aung, Tin; Young, Terri L; Tideman, J Willem L; Jonas, Jost B.; Mitchell, Paul; Wojciechowski, Robert; Stambolian, Dwight; Hysi, Pirro G.; Hammond, Christopher J.; Mackey, David A; Lucas, Robyn M; MacGregor, Stuart; Consortium for Refractive Error and Myopia (CREAM).

In: International Journal of Epidemiology, Vol. 46, No. 6, 01.12.2017, p. 1882–1890.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Genetically low vitamin D concentrations and myopic refractive error

T2 - a Mendelian randomization study

AU - Cuellar-Partida, Gabriel

AU - Williams, Katie M

AU - Yazar, Seyhan

AU - Guggenheim, Jeremy A

AU - Hewitt, Alex W

AU - Williams, Cathy

AU - Wang, Jie Jin

AU - Kho, Pik-Fang

AU - Saw, Seang Mei

AU - Cheng, Ching Yu

AU - Wong, Tien Yin

AU - Aung, Tin

AU - Young, Terri L

AU - Tideman, J Willem L

AU - Jonas, Jost B.

AU - Mitchell, Paul

AU - Wojciechowski, Robert

AU - Stambolian, Dwight

AU - Hysi, Pirro G.

AU - Hammond, Christopher J.

AU - Mackey, David A

AU - Lucas, Robyn M

AU - MacGregor, Stuart

AU - Consortium for Refractive Error and Myopia (CREAM)

PY - 2017/12/1

Y1 - 2017/12/1

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.1093/ije/dyx068

DO - 10.1093/ije/dyx068

M3 - Article

VL - 46

SP - 1882

EP - 1890

JO - International Journal of Epidemiology

JF - International Journal of Epidemiology

SN - 0300-5771

IS - 6

ER -