Evidence map›Paper›PMID 30642396›Full record

ArticleClinical epigenetics2019

Whole-genome methylation profiling of the retinal pigment epithelium of individuals with age-related macular degeneration reveals differential methylation of the SKI, GTF2H4, and TNXB genes.

Louise F Porter, Neil Saptarshi, Yongxiang Fang, Sonika Rathi, Anneke I den Hollander, Eiko K de Jong, Simon J Clark, Paul N Bishop, Timothy W Olsen, Triantafillos Liloglou and 2 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical epigenetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
7.4field-weighted citation impact, top 2% 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

37 citing papers in PubMed, 58 citations in OpenAlex.

  1. Article
  2. Review
  3. Dysregulated DNA Methylation inInternational journal of molecular sciences · 2025
    Article
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  15. Epigenetic Switches in Retinal Homeostasis and Target for Drug Development.International journal of molecular sciences · 2024
    Review
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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

12 authors at 6 institutions in 3 countries.

Louise F PorterSt Paul's Eye Unit, Royal Liverpool University Hospital, Liverpool, UK. louise.porter@liverpool.ac.uk.ORCID 0000-0002-7406-0319
Neil SaptarshiDepartment of Eye and Vision Science, William Duncan Building, University of Liverpool, Liverpool, UK.
Yongxiang FangCentre for Genomic Research, University of Liverpool, Liverpool, UK.
Sonika RathiDepartment of Ophthalmology, University of Pennsylvania School of Medicine, Philadelphia, USA.
Anneke I den HollanderDepartment of Ophthalmology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.
Eiko K de JongDepartment of Ophthalmology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.
Simon J ClarkDivision of Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
Paul N BishopDivision of Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
Timothy W OlsenMayo Clinic, Rochester, MN, USA.
Triantafillos LiloglouInstitute of Translational Medicine, University of Liverpool, Liverpool, UK.
Venkata R M ChavaliDepartment of Ophthalmology, University of Pennsylvania School of Medicine, Philadelphia, USA.
Luminita ParaoanDepartment of Eye and Vision Science, William Duncan Building, University of Liverpool, Liverpool, UK.
University of Liverpool · GBRadboud University Nijmegen · NLUniversity of Pennsylvania · USManchester Academic Health Science Centre · GBMayo Clinic in Arizona · USUniversity of Manchester · GB

Funding

Deciphering the role of lipid metabolism pathways in the RPE and their implications for AMDR21EY028273 · NEI · UNIVERSITY OF PENNSYLVANIA · PI CHAVALI, VENKATA RAMANA MURTHY · 2018 to 2019
$443k
Medical Research Council MR/K024418/1NEI NIH HHS R21 EY028273
6 · The paper itself

Abstract

backgroundAge-related macular degeneration (AMD) is a degenerative disorder of the central retina and the foremost cause of blindness. The retinal pigment epithelium (RPE) is a primary site of disease pathogenesis. The genetic basis of AMD is relatively well understood; however, this knowledge is yet to yield a treatment for the most prevalent non-neovascular disease forms. Therefore, tissue-specific epigenetic mechanisms of gene regulation are of considerable interest in AMD. We aimed to identify differentially methylated genes associated with AMD in the RPE and differentiate local DNA methylation aberrations from global DNA methylation changes, as local DNA methylation changes may be more amenable to therapeutic manipulation.

methodsEpigenome-wide association study and targeted gene expression profiling were carried out in RPE cells from eyes of human donors. We performed genome-wide DNA methylation profiling (Illumina 450k BeadChip array) on RPE cells from 44 human donor eyes (25 AMD and 19 normal controls). We validated the findings using bisulfite pyrosequencing in 55 RPE samples (30 AMD and 25 normal controls) including technical (n = 38) and independent replicate samples (n = 17). Long interspersed nucleotide element 1 (LINE-1) analysis was then applied to assess global DNA methylation changes in the RPE. RT-qPCR on independent donor RPE samples was performed to assess gene expression changes.

resultsGenome-wide DNA methylation profiling identified differential methylation of multiple loci including the SKI proto-oncogene (SKI) (p = 1.18 × 10

conclusionsWe report the largest genome-wide methylation analysis of RPE in AMD along with associated gene expression changes to date, for the first-time reaching genome-wide significance, and identified novel targets for functional and future therapeutic intervention studies. The novel differentially methylated genes SKI and GTF2H4 have not been previously associated with AMD, and regulate disease pathways implicated in AMD, including TGF beta signaling (SKI) and transcription-dependent DNA repair mechanisms (GTF2H4).

Indexed as

DNA MethylationAgedAutopsyCase-Control StudiesDNA-Binding ProteinsEpigenesis, GeneticFemaleGene Expression ProfilingGene Expression RegulationGenetic Association StudiesHigh-Throughput Nucleotide SequencingHumansMacular DegenerationMaleMiddle AgedOrgan SpecificityDNA-Binding ProteinsGTF2H4 protein, humanMAS1 protein, humanProto-Oncogene MasProto-Oncogene ProteinsSKI protein, humanTenascintenascin XTranscription Factors, GeneralTranscription Factors, TFII

Identifiers

PMID30642396
PMCPMC6332695
OpenAlexW2919500061

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

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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.