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 |
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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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