Evidence map›Paper›PMID 28264060›Full record

ArticlePloS one2017

Whole exome sequencing implicates eye development, the unfolded protein response and plasma membrane homeostasis in primary open-angle glaucoma.

Tiger Zhou, Emmanuelle Souzeau, Shiwani Sharma, John Landers, Richard Mills, Ivan Goldberg, Paul R Healey, Stuart Graham, Alex W Hewitt, David A Mackey and 10 more

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

Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
7.5field-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

5 citing papers in PubMed, 49 citations in OpenAlex.

  1. Trial
  2. Review
  3. Review
  4. Review
  5. Glaucomagenesis following ionizing radiation exposure.Mutation research. Reviews in mutation research
    Review
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

20 authors at 8 institutions in 1 country.

Tiger ZhouFlinders University, Department of Ophthalmology, Bedford Park, South Australia, Australia.ORCID http://orcid.org/0000-0001-6495-8865
Emmanuelle SouzeauFlinders University, Department of Ophthalmology, Bedford Park, South Australia, Australia.
Shiwani SharmaFlinders University, Department of Ophthalmology, Bedford Park, South Australia, Australia.
John LandersFlinders University, Department of Ophthalmology, Bedford Park, South Australia, Australia.
Richard MillsFlinders University, Department of Ophthalmology, Bedford Park, South Australia, Australia.
Ivan GoldbergUniversity of Sydney Discipline of Ophthalmology, Sydney, Australia.
Paul R HealeyUniversity of Sydney Discipline of Ophthalmology, Sydney, Australia.
Stuart GrahamUniversity of Sydney Discipline of Ophthalmology, Sydney, Australia.
Alex W HewittUniversity of Tasmania Menzies Institute for Medical Research, Hobart, Australia.
David A MackeyUniversity of Western Australia Centre for Ophthalmology and Visual Science, Lions Eye Institute, Perth, Australia.
Anna GalanopoulosUniversity of Adelaide, Discipline of Ophthalmology & Visual Sciences, Adelaide, Australia.
Robert J CassonUniversity of Adelaide, Discipline of Ophthalmology & Visual Sciences, Adelaide, Australia.
Jonathan B RuddleCentre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Melbourne, Australia.
Jonathan EllisUniversity of Queensland Diamantina Institute, Translational Research Institute, Princess Alexandra Hospital, Woolloongabba, Australia.
Paul LeoUniversity of Queensland Diamantina Institute, Translational Research Institute, Princess Alexandra Hospital, Woolloongabba, Australia.
Matthew A BrownUniversity of Queensland Diamantina Institute, Translational Research Institute, Princess Alexandra Hospital, Woolloongabba, Australia.
Stuart MacGregorStatistical Genetics, QIMR Berghofer Medical Research Institute, Royal Brisbane Hospital, Brisbane, Australia.
David J LynnEMBL Australia Group, Infection & Immunity Theme, South Australian Medical and Health Research Institute, Adelaide, Australia.
Kathryn P BurdonFlinders University, Department of Ophthalmology, Bedford Park, South Australia, Australia.
Jamie E CraigFlinders University, Department of Ophthalmology, Bedford Park, South Australia, Australia.
Flinders University · AUThe University of Sydney · AUTranslational Research Institute · AUThe University of Adelaide · AUUniversity of Tasmania · AUCentre for Eye Research Australia · AULions Eye Institute · AUQIMR Berghofer Medical Research Institute · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeTo identify biological processes associated with POAG and its subtypes, high-tension (HTG) and normal-tension glaucoma (NTG), by analyzing rare potentially damaging genetic variants.

methodsA total of 122 and 65 unrelated HTG and NTG participants, respectively, with early onset advanced POAG, 103 non-glaucoma controls and 993 unscreened ethnicity-matched controls were included in this study. Study participants without myocilin disease-causing variants and non-glaucoma controls were subjected to whole exome sequencing on an Illumina HiSeq2000. Exomes of participants were sequenced on an Illumina HiSeq2000. Qualifying variants were rare in the general population (MAF < 0.001) and potentially functionally damaging (nonsense, frameshift, splice or predicted pathogenic using SIFT or Polyphen2 software). Genes showing enrichment of qualifying variants in cases were selected for pathway and network analysis using InnateDB.

resultsPOAG cases showed enrichment of rare variants in camera-type eye development genes (p = 1.40×10-7, corrected p = 3.28×10-4). Implicated eye development genes were related to neuronal or retinal development. HTG cases were significantly enriched for key regulators in the unfolded protein response (UPR) (p = 7.72×10-5, corrected p = 0.013). The UPR is known to be involved in myocilin-related glaucoma; our results suggest the UPR has a role in non-myocilin causes of HTG. NTG cases showed enrichment in ion channel transport processes (p = 1.05×10-4, corrected p = 0.027) including calcium, chloride and phospholipid transporters involved in plasma membrane homeostasis. Network analysis also revealed enrichment of the MHC Class I antigen presentation pathway in HTG, and the EGFR1 and cell-cycle pathways in both HTG and NTG.

conclusionThis study suggests that mutations in eye development genes are enriched in POAG. HTG can result from aberrant responses to protein misfolding which may be amenable to molecular chaperone therapy. NTG is associated with impaired plasma membrane homeostasis increasing susceptibility to apoptosis.

Indexed as

AdultApoptosisCase-Control StudiesCell MembraneComputational BiologyExomeFemaleGene Expression ProfilingGene Expression RegulationGene OntologyGene Regulatory NetworksGenetic Predisposition to DiseaseGlaucoma, Open-AngleHigh-Throughput Nucleotide SequencingHomeostasisHumans

Identifiers

PMID28264060
PMCPMC5338784
OpenAlexW2592746732

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.