Abstract
Purpose :
Strabismus is an important cause of vision loss in children. Often accompanied by substantial psychosocial consequences. Despite its significance, the underlying causes of strabismus remain elusive. In light of emerging evidence associating DNA methylation variations with childhood outcomes, we hypothesized that alterations in DNA methylation can influence the development of the visual system. Our study aimed to investigate whether DNA methylation patterns at birth can predict strabismus in preschool children.
Methods :
Archived neonatal blood spots were obtained for 1464 preschool children who participated in the Multiethnic Pediatric Eye Study through the California Department of Public Health. Ocular alignment was assessed using the unilateral cover test and alternate cover and prism test, both at distance and near fixation, with and without correction. Strabismus was defined as constant or intermittent heterotropia of any magnitude at distance or near fixation, or both, and was classified according to the horizontal direction (esotropia, exotropia) of the tropia. Genome-wide DNA methylation status was assessed using the Illumina Infinium® Methylation EPIC Array. We investigated differentially methylated CpG sites associated with strabismus at P<9.0×10-8.
Results :
112 children had exotropia (13 intermittent and 83 constant) and 98 had esotropia (50 intermittent and 48 constant). We identified 91 probes linked to strabismus, with 29 hypermethylated and 62 hypomethylated. Notably, specific probes exhibited substantial methylation difference with an absolute methylation delta beta greater than 0.10 (e.g., hypermethylation in WDR66, delta beta=0.28, P=4.8×10-12; hypomethylation in CCDC102A, delta beta=-0.15, P=1.1×10-9). While certain methylation differences were consistent across different strabismus subtype (e.g. WDR66), we also observed unique methylation profiles specific to each subtypes. For example, variations in DNA methylation were found in 39 probes across 18 genes (e.g., CCKBR) between constant and intermittent esotropia. Specifically, hypermethylation of four probes on the HOOK2 gene were distinctive to constant esotropia but remained unchanged in intermittent esotropia.
Conclusions :
Our findings suggest an association between alterations in DNA methylation in neonatal blood and the development of strabismus in preschool children.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.