Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0214791
Title: In-utero epigenetic factors are associated with early-onset myopia in young children
Authors: Seow WJ 
Ngo CS 
Pan H
Barathi VA 
Tompson SW 
Whisenhunt KN
Vithana E 
Chong YS 
Juo SH
Hysi P
Young TL 
Karnani N 
Saw SM 
Issue Date: 17-May-2019
Publisher: Public Library of Science
Citation: Seow WJ, Ngo CS, Pan H, Barathi VA, Tompson SW, Whisenhunt KN, Vithana E, Chong YS, Juo SH, Hysi P, Young TL, Karnani N, Saw SM (2019-05-17). In-utero epigenetic factors are associated with early-onset myopia in young children. PLoS One 14 (5) : e0214791. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0214791
Abstract: Objectives To 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. Methods Genome-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. Results We 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 intergenicregions: 8p23(p = 1.70-10-7) and 12q23.2(p = 2.53-10-7). The remaining 3 statistically significant CpG sites were identified within the following genes: FGB (4q28, p = 3.60-10-7), PQLC1 (18q23, p = 8.9-10-7) and KRT12 (17q21.2, p = 1.2-10-6). Both PQLC1 and KRT12 were found to be significantly expressed in fetal and adult cornea and sclera tissues in both human and mouse. Conclusions We 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. © 2019 Seow et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Source Title: PLoS One
URI: https://scholarbank.nus.edu.sg/handle/10635/162307
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0214791
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