Powered by OpenAIRE graph
image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Investigative Ophtha...arrow_drop_down
image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
Investigative Ophthalmology & Visual Science
Article . 2022 . Peer-reviewed
License: CC BY NC ND
Data sources: Crossref
image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
versions View all 3 versions

Decreased Levels of DNA Methylation in the PCDHA Gene Cluster as a Risk Factor for Early-Onset High Myopia in Young Children

Authors: Swierkowska, Joanna; Karolak, Justyna A.; Vishweswaraiah, Sangeetha; Mrugacz, Malgorzata; Radhakrishna, Uppala; Gajecka, Marzena;

Decreased Levels of DNA Methylation in the PCDHA Gene Cluster as a Risk Factor for Early-Onset High Myopia in Young Children

Abstract

High myopia (HM), an eye disorder with at least -6.0 diopters refractive error, has a complex etiology with environmental, genetic, and likely epigenetic factors involved. To complement the DNA methylation assessment in children with HM, we analyzed genes that had significantly lower DNA methylation levels.The DNA methylation pattern was studied based on the genome-wide methylation data of 18 Polish children with HM paired with 18 controls. Genes overlapping CG dinucleotides with decreased methylation level in HM cases were assessed by enrichment analyses. From those, genes with CG dinucleotides in promoter regions were further evaluated based on exome sequencing (ES) data of 16 patients with HM from unrelated Polish families, Sanger sequencing data of the studied children, and the RNA sequencing data of human retinal ARPE-19 cells.The CG dinucleotide with the most decreased methylation level in cases was identified in a promoter region of PCDHA10 that overlaps intronic regions of PCDHA1-9 of the PCDHA gene cluster in myopia 5q31 locus. Also, two single nucleotide variants, rs200661444, detected in our ES, and rs246073, previously found as associated with a refractive error in a genome-wide association study, were revealed within this gene cluster. Additionally, genes previously linked to ocular phenotypes, myopia-related traits, or loci, including ADAM20, ZFAND6, ETS1, ABHD13, SBSPON, SORBS2, LMOD3, ATXN1, and FARP2, were found to have decreased methylation.Alterations in the methylation pattern of specific CG dinucleotides may be associated with early-onset HM, so this could be used to develop noninvasive biomarkers of HM in children and adolescents.

Keywords

Adolescent, Risk Factors, Child, Preschool, Multigene Family, Genetics, Myopia, Guanine Nucleotide Exchange Factors, Humans, DNA Methylation, Child, Genome-Wide Association Study

  • BIP!
    Impact byBIP!
    citations
    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    7
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Average
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 10%
Powered by OpenAIRE graph
citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
7
Top 10%
Average
Top 10%
Green
gold