Abstract
Purpose :
Despite the disabling consequences of vision disorders (e.g., high hyperopia) in early childhood, their etiology remains mostly unknown, and these disorders tend to remain undetected until older ages. Given the importance of the establishment of epigenetic characteristics in fetal development and evidence linking alterations of DNA methylation with childhood outcomes such as low birth weight, we hypothesize that DNA methylation changes can alter the development of the vision system in the fetus. We evaluated whether DNA methylation at birth can predict refractive errors identified in 6-72-month-old children.
Methods :
Archived neonatal blood spots were obtained from the California Department of Public Health for 1464 preschool children who participated in the Multiethnic Pediatric Eye Study, including 370 non-Hispanic whites, 174 Hispanic whites, 824 African Americans, and 96 Asian Americans. Spherical equivalent (SE) refractive error was calculated based on cycloplegic refraction. Genome-wide DNA methylation status was assessed from the blood spots using the Illumina Infinium® Methylation EPIC Array. Epigenome-wide association was performed using multivariable linear regression, adjusted for sex, array plate, ancestry, and blood cell composition.
Results :
The mean age of the children was 48 (±14) months old, and the mean SE refractive error of the right eye was +1.7 (±1.9) diopters. We identified 7 differentially methylated regions (DMRs) significantly associated with SE refractive error in the right eyes and 13 DMRS associated with SE refractive error in the worse eye (more hyperopic). 6 DMRs (HOXA2, TMCO3, CDIPTOSP, DPP3, BSG, FAM120B) were found to be consistently associated with SE refractive error in the right eyes, left eyes, and the worse eyes. 5 of the 6 DMRs were hypermethylated, and one DMR (BSG) was hypomethylated with more hyperopic refractive error. These DMR genes were enriched for neurodevelopment in gene ontology classifiers and prior genetic studies of eye conditions.
Conclusions :
Distinct DNA methylation signatures can be detected in newborn blood before the diagnosis of refractive error (e.g., hyperopia) in children. Our results suggest that prenatal factors that influence DNA methylation in the fetus may play an essential role in pediatric eye diseases, with implications for predicting and preventing these diseases.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.