In-Utero Epigenetic Factors Are Associated With Early-Onset Myopia In Young Children
PLOS ONE(2019)
Abstract
ObjectivesTo assess whether epigenetic mechanisms affecting gene expression may be involved in the pathogenesis of early-onset myopia, we performed genome-wide DNA methylation analyses of umbilical cord tissues, and assessed any associations between CpG site-specific methylation and the development of the disorder when the children were 3 years old.MethodsGenome-wide DNA methylation profiling of umbilical cord samples from 519 Singaporean infants involved in a prospective birth cohort 'Growing Up in Singapore Towards healthy Outcomes' (GUSTO) was performed using the Illumina Infinium HumanMethylation450K chip microarray. Multivariable logistic regression models were used to assess any associations between site-specific CpG methylation of umbilical cord tissue at birth and myopia risk in 3 year old children, adjusting for potential confounders. Gene expression of genes located near CpG sites that demonstrated statistically significant associations were measured in relevant ocular tissues using human and mouse fetal and adult eye samples.ResultsWe identified statistically significant associations between DNA methylation levels at five CpG sites and early-onset myopia risk after correcting for multiple comparisons using a false discovery rate of 5%. Two statistically significant CpG sites were identified in intergenic regions: 8p23(p = 1.70x10(-7)) and 12q23.2(p = 2.53x10(-7)). The remaining 3 statistically significant CpG sites were identified within the following genes: FGB (4q28, p = 3.60x10(-7)), PQLC1 (18q23, p = 8.9x10(-7)) and KRT12 (17q21.2, p = 1.2x10(-6)). Both PQLC1 and KRT12 were found to be significantly expressed in fetal and adult cornea and sclera tissues in both human and mouse.ConclusionsWe identified five CpG methylation sites that demonstrate a statistically significant association with increased risk of developing early-onset myopia. These findings suggest that variability in the neonatal cord epigenome may influence early-onset myopia risk in children. Further studies of the epigenetic influences on myopia risk in larger study populations, and the associations with adulthood myopia risk are warranted.
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Key words
Childhood Myopia,Myopia
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