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

Sangeetha Vishweswaraiah, Joanna Swierkowska, Uppala Ratnamala, Nitish K. Mishra, Chittibabu Guda, Shiva S. Chettiar, Kaid R. Johar, Malgorzata Mrugacz, Justyna A. Karolak, Marzena Gajecka, Uppala Radhakrishna

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number4145
JournalScientific Reports
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2019

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Myopia
Genes
Methylation
Area Under Curve
Vision Disorders
DNA Methylation
Ethnic Groups
Epigenomics
ROC Curve
Public Health
Genome
Incidence
Population

ASJC Scopus subject areas

  • General

Cite this

Vishweswaraiah, S., Swierkowska, J., Ratnamala, U., Mishra, N. K., Guda, C., Chettiar, S. S., ... Radhakrishna, U. (2019). Epigenetically dysregulated genes and pathways implicated in the pathogenesis of non-syndromic high myopia. Scientific Reports, 9(1), [4145]. https://doi.org/10.1038/s41598-019-40299-x

Epigenetically dysregulated genes and pathways implicated in the pathogenesis of non-syndromic high myopia. / Vishweswaraiah, Sangeetha; Swierkowska, Joanna; Ratnamala, Uppala; Mishra, Nitish K.; Guda, Chittibabu; Chettiar, Shiva S.; Johar, Kaid R.; Mrugacz, Malgorzata; Karolak, Justyna A.; Gajecka, Marzena; Radhakrishna, Uppala.

In: Scientific Reports, Vol. 9, No. 1, 4145, 01.12.2019.

Research output: Contribution to journalArticle

Vishweswaraiah, S, Swierkowska, J, Ratnamala, U, Mishra, NK, Guda, C, Chettiar, SS, Johar, KR, Mrugacz, M, Karolak, JA, Gajecka, M & Radhakrishna, U 2019, 'Epigenetically dysregulated genes and pathways implicated in the pathogenesis of non-syndromic high myopia', Scientific Reports, vol. 9, no. 1, 4145. https://doi.org/10.1038/s41598-019-40299-x
Vishweswaraiah, Sangeetha ; Swierkowska, Joanna ; Ratnamala, Uppala ; Mishra, Nitish K. ; Guda, Chittibabu ; Chettiar, Shiva S. ; Johar, Kaid R. ; Mrugacz, Malgorzata ; Karolak, Justyna A. ; Gajecka, Marzena ; Radhakrishna, Uppala. / Epigenetically dysregulated genes and pathways implicated in the pathogenesis of non-syndromic high myopia. In: Scientific Reports. 2019 ; Vol. 9, No. 1.
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