Epigenetically dysregulated genes and pathways implicated in the pathogenesis of non-syndromic high myopia

Abstract

Myopia, commonly referred to as nearsightedness, is one of the most common causes of visual disability throughout the world. It affects more people worldwide than any other chronic visual impairment condition. Although the prevalence varies among various ethnic groups, the incidence of myopia is increasing in all populations across globe. Thus, it is considered a pressing public health problem. Both genetics and environment play a role in development of myopia. To elucidate the epigenetic mechanism(s) underlying the pathophysiology of high-myopia, we conducted methylation profiling in 18 cases and 18 matched controls (aged 4–12 years), using Illumina MethylationEPIC BeadChips array. The degree of myopia was variable among subjects, ranging from −6 to −15D. We identified 1541 hypermethylated CpGs, representing 1745 genes (2.0-fold or higher) (false discovery rate (FDR) p ≤ 0.05), multiple CpGs were p < 5 × 10−8 with a receiver operating characteristic area under the curve (ROC-AUC) ≥ 0.75 in high-myopia subjects compared to controls. Among these, 48 CpGs had excellent correlation (AUC ≥ 0.90). Herein, we present the first genome-wide DNA methylation analysis in a unique high-myopia cohort, showing extensive and discrete methylation changes relative to controls. The genes we identified hold significant potential as targets for novel therapeutic intervention either alone, or in combination.

IMI 2021 Yearly Digest

“… 100 The PubMed database was searched using various MeSH terms (e.g., “myopia/genetics,” “refractive errors/genetics,” “genetic predisposition to disease”) to identify articles published between February 2019 and April 2020. Most of these articles focused on gene-discovery in (pathologic) myopia 101 – 104 the genetic overlap with myopia-related complications, 105 , 106 , 126 epigenetics, 78 , 85 , 107 , 108 transcriptomics, 109 – 113 proteomics 113 , 114 , 120 and the interaction between environmental factors and genetics. 115 , 116 The key advances are highlighted below in Figure 2 .…”

“…Vishweswaraiah et al. 108 studied epigenetic differences in 18 children aged 4 to 12 years with a high degree of myopia (SER ≤ –6 D) and 18 healthy controls from 1 Polish center. The authors identified 1541 CpG sites in 1745 unique genes with a 2-fold or higher differential methylation in the high-myopia cases compared to controls.…”

“… 78 , 85 , 107 – 114 , 120 As discussed, 3 human epigenetic myopia studies were published in the past year. 85 , 107 , 108 Epigenetics might allow greater understanding of how the environment causes myopia but may require prospective longitudinal studies to investigate changes of methylation signatures during life. In healthy volunteers, we are usually limited to data from blood.…”

Mechanism for epeirogenic uplift of the Archean Dharwar craton, southern India as evidenced by orthogonal seismic reflection profiles

“…Thus, we interpret, the magmatic underplating identified here generated isostatic uplift and responsible for the epeirogenic uplift in the region. Radhakrishna et al 42 suggest igneous underplating is responsible for the plateau uplift in the region. Mantle plume/hotspot related uplift is a major tectonic process that covers 10% of the earth’s surface.…”

Genome-wide analysis of retinal transcriptome reveals common genetic network underlying perception of contrast and optical defocus detection

“…We found that contrast perception is strongly dependent on the signaling pathways in humans (116,117). In-utero epigenetic factors were found to be associated with refractive status in young children, and grandmothers' smoking causing epigenetic modifications of the genome was shown to be linked to less myopic refractive errors in children (118)(119)(120)(121)(122).…”