Investigative Ophthalmology & Visual Science Cover Image for Volume 59, Issue 9
July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Gene-Based Analysis Leveraging Whole Genome Sequencing (WGS) Data on Individuals with Multiple Longitudinal Glaucoma Related Phenotypes Shows Evidence for Genetic Factors in Open Angle Glaucoma Progression
Argus J Athanas-Crannell; Mark Christopher; Yongwook Choi; Agnes Chan; Linda M Zangwill; Jerome I Rotter; Jeffrey M Liebmann; Christopher A Girkin; Robert M Feldman; Harvey Dubiner; Yii-Der Ida Chen; Kent Taylor; Xiuqing Guo; Radha Ayyagari; Robert N Weinreb; Nicholas Schork
Author Affiliations & Notes
  • Argus J Athanas-Crannell
    Biomedical Informatics, University California San Diego , San Diego, California, United States
  • Mark Christopher
    Hamilton Glaucoma Center, Shiley Eye Institute, Department of Ophthalmology, University of California San Diego, La Jolla, California, United States
  • Yongwook Choi
    Human Biology, The J. Craig Venter Institute, La Jolla, California, United States
  • Agnes Chan
    Human Biology, The J. Craig Venter Institute, La Jolla, California, United States
  • Linda M Zangwill
    Hamilton Glaucoma Center, Shiley Eye Institute, Department of Ophthalmology, University of California San Diego, La Jolla, California, United States
  • Jerome I Rotter
    Los Angeles Biomedical Research Institute and Department of Pediatrics, Institute for Translational Genomics and Population Sciences, Torrance, California, United States
  • Jeffrey M Liebmann
    Bernard and Shirlee Brown Glaucoma Research Laboratory, Harkness Eye Institute, New York, New York, United States
  • Christopher A Girkin
    Department of Ophthalmology, University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Robert M Feldman
    Ruiz Department of Ophthalmology, University of Texas Health Science Center, Houston, Texas, United States
  • Harvey Dubiner
    Eye Care Center Management Inc, Marrow, Georgia, United States
  • Yii-Der Ida Chen
    Los Angeles Biomedical Research Institute and Department of Pediatrics, Institute for Translational Genomics and Population Sciences, Torrance, California, United States
  • Kent Taylor
    Los Angeles Biomedical Research Institute and Department of Pediatrics, Institute for Translational Genomics and Population Sciences, Torrance, California, United States
  • Xiuqing Guo
    Los Angeles Biomedical Research Institute and Department of Pediatrics, Institute for Translational Genomics and Population Sciences, Torrance, California, United States
  • Radha Ayyagari
    Hamilton Glaucoma Center, Shiley Eye Institute, Department of Ophthalmology, University of California San Diego, La Jolla, California, United States
  • Robert N Weinreb
    Hamilton Glaucoma Center, Shiley Eye Institute, Department of Ophthalmology, University of California San Diego, La Jolla, California, United States
  • Nicholas Schork
    Hamilton Glaucoma Center, Shiley Eye Institute, Department of Ophthalmology, University of California San Diego, La Jolla, California, United States
    Departments of Psychiatry and Family Medicine and Public Health, University of California San Diego, La Jolla, California, United States
  • Footnotes
    Commercial Relationships   Argus Athanas-Crannell, None; Mark Christopher, None; Yongwook Choi, None; Agnes Chan, None; Linda Zangwill, EyeSight Foundation of Alabama (F), GmbH (F), Heidelberg Engineering (F), National Eye Institute (F), Research to Prevent Blindness (F); Jerome Rotter, None; Jeffrey Liebmann, Alcon, Inc. (C), Allergan, Inc. (C), Bausch & Lomb (F), Bausch & Lomb, Inc. (C), Carl Zeiss Meditec (F), Carl Zeiss Meditech, Inc. (C), GmbH (C), Heidelberg Engineering (C), Heidelberg Engineering (F), National Eye Institute (F), Optovue (F), Reichert (C), Reichert (F), Topcon (F), Valeant Pharmaceuticals (C); Christopher Girkin, EyeSight Foundation of Alabama (F), GmbH (F), Heidelberg Engineering (F), National Eye Institute (F), Research to Prevent Blindness (F); Robert Feldman, None; Harvey Dubiner, None; Yii-Der Chen, None; Kent Taylor, None; Xiuqing Guo, None; Radha Ayyagari, None; Robert Weinreb, Aerie Pharmaceuticals (C), Alcon (C), Allergan (C), Bausch & Lomb (C), Carl Zeiss Meditec (F), Centervue (F), Eyenovia (C), Genentech (F), Heidelberg Engineering (F), Konan (F), Novartis (C), Optos (F), Optovue (F), Sensimed (C), Topcon (F), Unity (C), Valeant (C); Nicholas Schork, None
  • Footnotes
    Support  NLM T15 grant NIH/NLM T15LM011271, EY023704, P30EY022589, EY110008, EY021237, EY019869, EY026590, EY027510 EY021818; Dr. Schork and his lab are supported in part by NIH/NIA grants 2 U19 AG023122 and U24AG051129, NIH/NCATS grant UL1TR001442, as well as Johnson and Johnson, Inc. Unrestricted grant from Research to Prevent Blindness, New York, New York
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 1182. doi:
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      Argus J Athanas-Crannell, Mark Christopher, Yongwook Choi, Agnes Chan, Linda M Zangwill, Jerome I Rotter, Jeffrey M Liebmann, Christopher A Girkin, Robert M Feldman, Harvey Dubiner, Yii-Der Ida Chen, Kent Taylor, Xiuqing Guo, Radha Ayyagari, Robert N Weinreb, Nicholas Schork; Gene-Based Analysis Leveraging Whole Genome Sequencing (WGS) Data on Individuals with Multiple Longitudinal Glaucoma Related Phenotypes Shows Evidence for Genetic Factors in Open Angle Glaucoma Progression. Invest. Ophthalmol. Vis. Sci. 2018;59(9):1182.

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Abstract

Purpose : To evaluate the relationship between genetic variants obtained from WGS and multiple glaucomatous visual field progression phenotypes.

Methods : WGS data was collected at an average read depth of 30x using the Illumina X10 technology on 600 glaucoma patients or glaucoma suspects of Northern European descent, and 71 normal controls. We focused our analyses on a subset of 440 glaucoma patients who had longitudinal visual field (VF) test results available (4.5 –12 years) allowing us to assess genetic factors contributing to glaucoma progression with VF summary measures and Garway-Heath visual field (GHVF) sector based loss of VF mean sensitivity or increase in the number of test locations outside normal limits (p<0.05) for pattern deviation. 6.2 Million SNPs were selected for analysis based on filters for Minor Allele Frequency (MAF > 5%), Hardy-Weinberg Equilibrium (HWE), and total called genotypes across all loci interrogated (> 90%). Using regression analysis techniques, we tested SNP associations against disease progression of GHVF sectors. Results from each GWAS on GHVF phenotypes were aggregated within genes and genic/intergenic regions, and SNPs that were above a genome-wide suggestive threshold (p < 1e-5) and with sufficient Linkage Disequilibrium LD support were selected for further analysis. A gene-based analysis was performed by looking at enrichment of significant SNPs across multiple phenotypes.

Results : Three genes previously shown to be associated with glaucoma, TMTC2 (p =1.622e-06), NR2F2 (p =3.365e-06), and ABCA1 (p =1.705e-04), exhibited evidence for association with multiple glaucoma progression glaucoma measures. Other intergenic regions, with no previous association to the disease were identified as novel influential loci. The strongest candidate, is between CCDC85A-VRK2 (p =8.984e-07). CCDC85A is paralog to CCDC85C which plays a role in radial glia maintenance.

Conclusions : Our data confirms known glaucoma genes that harbor variants are associated with disease progression in addition to a wide variety of Glaucoma-related phenotypes in European population.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
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Copyright © 2025 Association for Research in Vision and Ophthalmology.
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