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dc.contributor.authorKhawaja, Anthony Pen
dc.contributor.authorChan, Michelle PYen
dc.contributor.authorYip, Jennifer LYen
dc.contributor.authorBroadway, David Cen
dc.contributor.authorGarway-Heath, David Fen
dc.contributor.authorViswanathan, Ananth Cen
dc.contributor.authorLuben, Roberten
dc.contributor.authorHayat, Shabinaen
dc.contributor.authorHauser, Michael Aen
dc.contributor.authorWareham, Nicholasen
dc.contributor.authorKhaw, Kay-Teeen
dc.contributor.authorFortune, Braden
dc.contributor.authorAllingham, R Randen
dc.contributor.authorFoster, Paul Jen
dc.date.accessioned2018-10-03T04:45:04Z
dc.date.available2018-10-03T04:45:04Z
dc.date.issued2018-09en
dc.identifier.issn1057-0829
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/283080
dc.description.abstractPURPOSE: A 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. METHODS: We 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. RESULTS: In 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. CONCLUSIONS: The protein coding SIX6 variant rs33912345, previously associated with POAG, has a functional effect on glaucoma-associated optic nerve head traits in Europeans.
dc.description.sponsorshipEPIC-Norfolk infrastructure and core functions are supported by grants from the Medical Research Council (G1000143) and Cancer Research UK (C864/A14136). The clinic for the third health examination was funded by Research into Ageing (262). Genotyping was funded by the Medical Research Council (MC_PC_13048). Mr Khawaja is supported by a Moorfields Eye Charity grant. Miss Chan is a joint Medical Research Council/Royal College of Ophthalmologists Research Fellow, and received additional support from the International Glaucoma Association. Professor Foster has received additional support from the Richard Desmond Charitable Trust (via Fight for Sight) and the Department for Health through the award made by the National Institute for Health Research to Moorfields Eye Hospital and the UCL Institute of Ophthalmology for a specialist Biomedical Research Centre for Ophthalmology.
dc.format.mediumPrinten
dc.languageengen
dc.subjectNerve Fibersen
dc.subjectRetinal Ganglion Cellsen
dc.subjectOptic Disken
dc.subjectHumansen
dc.subjectOptic Nerve Diseasesen
dc.subjectGlaucoma, Open-Angleen
dc.subjectHomeodomain Proteinsen
dc.subjectTrans-Activatorsen
dc.subjectTonometry, Ocularen
dc.subjectGenotypeen
dc.subjectMutation, Missenseen
dc.subjectAgeden
dc.subjectMiddle Ageden
dc.subjectEuropean Continental Ancestry Groupen
dc.subjectFemaleen
dc.subjectMaleen
dc.subjectScanning Laser Polarimetryen
dc.titleA Common Glaucoma-risk Variant of SIX6 Alters Retinal Nerve Fiber Layer and Optic Disc Measures in a European Population: The EPIC-Norfolk Eye Study.en
dc.typeArticle
prism.endingPage749
prism.issueIdentifier9en
prism.publicationDate2018en
prism.publicationNameJournal of glaucomaen
prism.startingPage743
prism.volume27en
dc.identifier.doi10.17863/CAM.30442
dcterms.dateAccepted2018-07-07en
rioxxterms.versionofrecord10.1097/ijg.0000000000001026en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2018-09en
dc.contributor.orcidKhawaja, Anthony P [0000-0001-6802-8585]
dc.contributor.orcidLuben, Robert [0000-0002-5088-6343]
dc.contributor.orcidWareham, Nicholas [0000-0003-1422-2993]
dc.contributor.orcidKhaw, Kay-Tee [0000-0002-8802-2903]
dc.contributor.orcidFortune, Brad [0000-0003-0284-5173]
dc.contributor.orcidFoster, Paul J [0000-0002-4755-177X]
dc.identifier.eissn1536-481X
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMRC (MC_UU_12015/1)
pubs.funder-project-idMRC (MC_PC_13048)
pubs.funder-project-idDepartment of Health (via National Institute for Health Research (NIHR)) (NF-SI-0512-10135)
pubs.funder-project-idDepartment of Health (via National Institute for Health Research (NIHR)) (NF-SI-0617-10149)
pubs.funder-project-idMRC (G1000143)
rioxxterms.freetoread.startdate2019-09-30


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