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 |
|---|---|
| Pages (from-to) | 1882–1890 |
| Journal | International Journal of Epidemiology |
| Volume | 46 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - 1 Dec 2017 |
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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 journal › Article
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 -