Evidence map›Paper›PMID 30005032›Full record

ArticleJournal of glaucoma2018

A Common Glaucoma-risk Variant of SIX6 Alters Retinal Nerve Fiber Layer and Optic Disc Measures in a European Population: The EPIC-Norfolk Eye Study.

Anthony P Khawaja, Michelle P Y Chan, Jennifer L Y Yip, David C Broadway, David F Garway-Heath, Ananth C Viswanathan, Robert Luben, Shabina Hayat, Michael A Hauser, Nicholas J Wareham and 4 more

Open access · greenAbstract read
In one paragraph

Article in Journal of glaucoma, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed, 2 pooled it
1.9field-weighted citation impact, top 15% 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

9 citing papers in PubMed, 2 syntheses or guidelines pooled it, 16 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Article
  4. NovelMolecular vision · 2022
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  5. Coinheritance ofWorld journal of clinical cases · 2021
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  6. Review
  7. Article
  8. Cell atlas of aqueous humor outflow pathways in eyes of humans and four model species provides insight into glaucoma pathogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  9. 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

14 authors at 8 institutions in 3 countries.

Anthony P KhawajaNIHR Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology.
Michelle P Y ChanDivision of Genetics and Epidemiology, UCL Institute of Ophthalmology, London.
Jennifer L Y YipDepartment of Public Health & Primary Care, University of Cambridge.
David C BroadwayDepartment of Ophthalmology, Norfolk and & Norwich University Hospital, Norwich, UK.
David F Garway-HeathNIHR Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology.
Ananth C ViswanathanNIHR Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology.
Robert LubenDepartment of Public Health & Primary Care, University of Cambridge.
Shabina HayatDepartment of Public Health & Primary Care, University of Cambridge.
Michael A HauserDepartment of Ophthalmology, Duke University Medical Center.
Nicholas J WarehamMRC Epidemiology Unit, Addenbrookes Hospital, Cambridge.
Kay-Tee KhawDepartment of Public Health & Primary Care, University of Cambridge.
Brad FortuneDevers Eye Institute and Legacy Research Institute, Portland, OR.
R Rand AllinghamDepartment of Ophthalmology, Duke University Medical Center.
Paul J FosterNIHR Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology.
University of Cambridge · GBDuke Medical Center · USMoorfields Eye Hospital NHS Foundation Trust · GBAddenbrooke's Hospital · GBInstitute of Ophthalmology · MXLegacy Health · USNorfolk and Norwich University Hospital · GBUniversity College London · GB

Funding

Data commons for 'omic, microscopy and analysis core facilitiesS10OD018164 · OD · DUKE UNIVERSITY · PI WRAY, GREGORY A. · 2014 to 2014
$598k
Cancer Research UK C864/A14136Department of HealthMedical Research Council G1000143Medical Research Council G1001939Medical Research Council MC_PC_13048Medical Research Council MC_PC_17228Medical Research Council MC_QA137853Medical Research Council MC_UU_12015/1NIH HHS S10 OD018164
6 · The paper itself

Abstract

purposeA common missense variant in the SIX6 gene (rs33912345) is strongly associated with primary open-angle glaucoma (POAG). We aimed to examine the association of rs33912345 with optic disc and retinal nerve fiber layer (RNFL) measures in a European population.

methodsWe examined participants of the population-based EPIC-Norfolk Eye Study. Participants underwent confocal laser scanning tomography (Heidelberg Retina Tomograph II, HRT) to estimate optic disc rim area and vertical cup-disc ratio (VCDR). Scanning laser polarimetry (GDxVCC) was used to estimate average RNFL thickness. The mean of right and left eye values was considered for each participant. Genotyping was performed using the Affymetrix UK Biobank Axiom Array. Multivariable linear regression with the optic nerve head parameter as outcome variable and dosage of rs33912345 genotype as primary explanatory variable was used, adjusted for age, sex, disc area, axial length, and intraocular pressure. We further repeated analyses stratified into age tertiles.

resultsIn total, 5433 participants with HRT data and 3699 participants with GDxVCC data were included. Each "C" allele of rs33912345 was associated with a smaller rim area (-0.030 mm [95% CI -0.040, -0.020]; P=5.4×10), a larger VCDR (0.025 [95% CI 0.017, 0.033]; P=3.3×10) and a thinner RNFL (-0.39 μm [95% CI -0.62, -0.15]; P=0.001). The RNFL association was strongest in the oldest age tertile, whereas rim area and VCDR associations were strongest in the youngest and oldest age tertiles.

conclusionsThe protein-coding SIX6 variant rs33912345, previously associated with POAG, has a functional effect on glaucoma-associated optic nerve head traits in Europeans.

Indexed as

Mutation, MissenseAgedFemaleGenotypeGlaucoma, Open-AngleHomeodomain ProteinsHumansMaleMiddle AgedNerve FibersOptic DiskOptic Nerve DiseasesRetinal Ganglion CellsScanning Laser PolarimetryTonometry, OcularTrans-ActivatorsHomeodomain ProteinsSIX6 protein, humanTrans-Activators

Identifiers

PMID30005032
PMCPMC6119604
OpenAlexW2883037864

What OpenQuestion holds

Textmetadata
LicenceTDM
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.