Evidence map›Paper›PMID 31100065›Full record

ArticlePloS one2019

In-utero epigenetic factors are associated with early-onset myopia in young children.

Wei Jie Seow, Cheryl S Ngo, Hong Pan, Veluchamy Amutha Barathi, Stuart W Tompson, Kristina N Whisenhunt, Eranga Vithana, Yap-Seng Chong, Suh-Hang H Juo, Pirro Hysi and 3 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed, 1 pooled it
2.6field-weighted citation impact, top 11% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.

  1. Pooled it
  2. Research Progress of Epigenetic Modifications in Myopia.International journal of medical sciences · 2025
    Review
  3. Article
  4. Article
  5. Article
  6. Article
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  8. Article
  9. Review
  10. Article
  11. IMI 2021 Yearly Digest.Investigative ophthalmology & visual science · 2021
    Review
  12. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 7 institutions in 4 countries.

Wei Jie SeowSaw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore.ORCID 0000-0002-9114-854X
Cheryl S NgoDepartment of Ophthalmology, National University Health System, Singapore.
Hong PanSingapore Institute for Clinical Sciences (SICS), A*STAR, Brenner Centre for Molecular Medicine, Singapore.
Veluchamy Amutha BarathiSingapore Eye Research Institute, Singapore.
Stuart W TompsonDepartment of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.ORCID 0000-0001-9788-6730
Kristina N WhisenhuntDepartment of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
Eranga VithanaSingapore Eye Research Institute, Singapore.
Yap-Seng ChongDepartment of Obstetrics and Gynaecology, National University of Singapore, Singapore, Singapore.
Suh-Hang H JuoInstitute of New Drug Development, Center for Myopia and Eye diseases, China Medical University and China Medical University Hospital, Taichung, Taiwan.
Pirro HysiDepartment of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom.
Terri L YoungDepartment of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
Neerja KarnaniSingapore Institute for Clinical Sciences (SICS), A*STAR, Brenner Centre for Molecular Medicine, Singapore.
Seang Mei SawSaw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore.
National University of Singapore · SGUniversity of Wisconsin–Madison · USAgency for Science, Technology and Research · SGChina Medical University · TWJohns Hopkins University · USNational University Health System · SGSingapore Eye Research Institute · SG

Funding

The Molecular Genetics of High MyopiaR01EY014685 · NEI · UNIVERSITY OF WISCONSIN-MADISON · PI YOUNG, TERRI LOIS · 2003 to 2017
$8.1M
International Collaborative Twin Study of Refractive and Glaucoma EndophenotypesR01EY018246 · NEI · DUKE UNIVERSITY · PI YOUNG, TERRI LOIS · 2007 to 2009
$1.8M
NEI NIH HHS R01 EY014685NEI NIH HHS R01 EY018246
6 · The paper itself

Abstract

objectivesTo assess whether epigenetic mechanisms affecting gene expression may be involved in the pathogenesis of early-onset myopia, we performed genome-wide DNA methylation analyses of umbilical cord tissues, and assessed any associations between CpG site-specific methylation and the development of the disorder when the children were 3 years old.

methodsGenome-wide DNA methylation profiling of umbilical cord samples from 519 Singaporean infants involved in a prospective birth cohort 'Growing Up in Singapore Towards healthy Outcomes' (GUSTO) was performed using the Illumina Infinium HumanMethylation450K chip microarray. Multivariable logistic regression models were used to assess any associations between site-specific CpG methylation of umbilical cord tissue at birth and myopia risk in 3 year old children, adjusting for potential confounders. Gene expression of genes located near CpG sites that demonstrated statistically significant associations were measured in relevant ocular tissues using human and mouse fetal and adult eye samples.

resultsWe identified statistically significant associations between DNA methylation levels at five CpG sites and early-onset myopia risk after correcting for multiple comparisons using a false discovery rate of 5%. Two statistically significant CpG sites were identified in intergenic regions: 8p23(p = 1.70×10-7) and 12q23.2(p = 2.53×10-7). The remaining 3 statistically significant CpG sites were identified within the following genes: FGB (4q28, p = 3.60×10-7), PQLC1 (18q23, p = 8.9×10-7) and KRT12 (17q21.2, p = 1.2×10-6). Both PQLC1 and KRT12 were found to be significantly expressed in fetal and adult cornea and sclera tissues in both human and mouse.

conclusionsWe identified five CpG methylation sites that demonstrate a statistically significant association with increased risk of developing early-onset myopia. These findings suggest that variability in the neonatal cord epigenome may influence early-onset myopia risk in children. Further studies of the epigenetic influences on myopia risk in larger study populations, and the associations with adulthood myopia risk are warranted.

Indexed as

Epigenesis, GeneticAnimalsChild, PreschoolCpG IslandsDisease Models, AnimalDNA MethylationEyeFemaleFibrinogenGene Expression RegulationGenome-Wide Association StudyHumansKeratin-12MaleMiceMice, Inbred C57BLFGB protein, humanFibrinogenKeratin-12KRT12 protein, human

Identifiers

PMID31100065
PMCPMC6524791
OpenAlexW2946486695

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.