In-utero epigenetic factors are associated with early-onset myopia in young children

Autor: Kristina N. Whisenhunt, Eranga N. Vithana, Neerja Karnani, Cheryl Ngo, Terri L. Young, Wei Jie Seow, Hong Pan, Stuart W. Tompson, Veluchamy A Barathi, Pirro G. Hysi, Seang-Mei Saw, Yap Seng Chong, Suh-Hang H. Juo
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Male
Embryology
Microarray
Physiology
Genome-wide association study
Eye
Umbilical cord
Biochemistry
Umbilical Cord
Epigenesis
Genetic
Cornea
Mice
0302 clinical medicine
Risk Factors
Medicine and Health Sciences
Myopia
Medicine
Visual Impairments
Multidisciplinary
DNA methylation
Methylation
Chromatin
3. Good health
Nucleic acids
medicine.anatomical_structure
CpG site
Child
Preschool
Epigenetics
Female
Anatomy
DNA modification
Chromatin modification
Research Article
Chromosome biology
Cell biology
Science
Ocular Anatomy
03 medical and health sciences
Ocular System
Genetics
Animals
Humans
Treatment Guidelines
Health Care Policy
Biology and life sciences
business.industry
Fibrinogen
Keratin-12
Epigenome
DNA
Health Care
Mice
Inbred C57BL
Ophthalmology
Disease Models
Animal
030104 developmental biology
Gene Expression Regulation
030221 ophthalmology & optometry
Eyes
CpG Islands
Gene expression
business
Head
Developmental Biology
Genome-Wide Association Study
Zdroj: PLoS ONE
PLoS ONE, Vol 14, Iss 5, p e0214791 (2019)
ISSN: 1932-6203
Popis: 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 = 1.70×10-7) 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.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.
Databáze: OpenAIRE
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