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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.

Publication ,  Journal Article
Khawaja, AP; Chan, MPY; Yip, JLY; Broadway, DC; Garway-Heath, DF; Viswanathan, AC; Luben, R; Hayat, S; Hauser, MA; Wareham, NJ; Khaw, K-T ...
Published in: J Glaucoma
September 2018

PURPOSE: 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.

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Published In

J Glaucoma

DOI

EISSN

1536-481X

Publication Date

September 2018

Volume

27

Issue

9

Start / End Page

743 / 749

Location

United States

Related Subject Headings

  • White People
  • Trans-Activators
  • Tonometry, Ocular
  • Scanning Laser Polarimetry
  • Retinal Ganglion Cells
  • Optic Nerve Diseases
  • Optic Disk
  • Ophthalmology & Optometry
  • Nerve Fibers
  • Mutation, Missense
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Khawaja, A. P., Chan, M. P. Y., Yip, J. L. Y., Broadway, D. C., Garway-Heath, D. F., Viswanathan, A. C., … Foster, P. J. (2018). 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. J Glaucoma, 27(9), 743–749. https://doi.org/10.1097/IJG.0000000000001026
Khawaja, Anthony P., Michelle P. Y. Chan, Jennifer L. Y. Yip, David C. Broadway, David F. Garway-Heath, Ananth C. Viswanathan, Robert Luben, et al. “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.J Glaucoma 27, no. 9 (September 2018): 743–49. https://doi.org/10.1097/IJG.0000000000001026.
Khawaja AP, Chan MPY, Yip JLY, Broadway DC, Garway-Heath DF, Viswanathan AC, et al. 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. J Glaucoma. 2018 Sep;27(9):743–9.
Khawaja, Anthony P., et al. “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.J Glaucoma, vol. 27, no. 9, Sept. 2018, pp. 743–49. Pubmed, doi:10.1097/IJG.0000000000001026.
Khawaja AP, Chan MPY, Yip JLY, Broadway DC, Garway-Heath DF, Viswanathan AC, Luben R, Hayat S, Hauser MA, Wareham NJ, Khaw K-T, Fortune B, Allingham RR, Foster PJ. 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. J Glaucoma. 2018 Sep;27(9):743–749.

Published In

J Glaucoma

DOI

EISSN

1536-481X

Publication Date

September 2018

Volume

27

Issue

9

Start / End Page

743 / 749

Location

United States

Related Subject Headings

  • White People
  • Trans-Activators
  • Tonometry, Ocular
  • Scanning Laser Polarimetry
  • Retinal Ganglion Cells
  • Optic Nerve Diseases
  • Optic Disk
  • Ophthalmology & Optometry
  • Nerve Fibers
  • Mutation, Missense