July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Genomic Architecture of POAG in Individuals of African Descent
--African Descent & Glaucoma Evaluation Study (ADAGESIII)--
Author Affiliations & Notes
  • Kent Taylor
    Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute, Torrance, California, United States
    Pediatrics, University of California Los Angeles, Los Angeles, California, United States
  • Xiuqing Guo
    Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute, Torrance, California, United States
  • Linda M Zangwill
    Department of Ophthalmology, Hamilton Glaucoma Center, Shiley Eye Institute, UC San Diego,, La Jolla, California, United States
  • Jeffrey M Liebmann
    Bernard and Shirlee Brown Glaucoma Research Laboratory, Harkness Eye Institute, Columbia University Medical Center, New York, New York, United States
  • Christopher A Girkin
    Department of Ophthalmology, University of Alabama at Birmingham, 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
  • Nicholette D Palmer
    Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States
    Center for Public Health Genomics, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States
  • Barry I Freedman
    Center for Public Health Genomics, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States
    Department of Internal Medicine, Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States
  • Donald W Bowden
    Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States
    Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States
  • Maggie CY Ng
    Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States
    Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States
  • Yii-Der Ida Chen
    Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute, Torrance, California, United States
    Pediatrics, University of California Los Angeles, Los Angeles, California, United States
  • Radha Ayyagari
    Department of Ophthalmology, Hamilton Glaucoma Center, Shiley Eye Institute, UC San Diego,, La Jolla, California, United States
  • Jerome I Rotter
    Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute, Torrance, California, United States
    Pediatrics, University of California Los Angeles, Los Angeles, California, United States
  • Robert N Weinreb
    Department of Ophthalmology, Hamilton Glaucoma Center, Shiley Eye Institute, UC San Diego,, La Jolla, California, United States
  • Footnotes
    Commercial Relationships   Kent Taylor, None; Xiuqing Guo, None; Linda Zangwill, Carl Zeiss Meditec Inc (F), Heidelberg Engineering (F), Merck (C), National Eye Institute (F), Optovue (F), Optovue (R), Topcon Medical Systems (F), Topcon Medical Systems (R); Jeffrey Liebmann, Alcon (C), Allergan (C), Bausch & Lomb (F), Bausch & Lomb, Inc (C), Carl Zeiss Meditec (F), Carl Zeiss Meditech (C), Heidelberg Engineering (C), Heidelberg Engineering (F), Optovue (F), Reichert (C), Reichert (F), Topcon (F), Valeant Pharmaceuticals (C); Christopher Girkin, EyeSight Foundation of Alabama (F), Heidelberg Engineering (F), National Eye Institute (F), Research to Prevent Blindness (F); Robert Feldman, None; Harvey Dubiner, None; Nicholette Palmer, None; Barry Freedman, None; Donald Bowden, None; Maggie Ng, None; Yii-Der Chen, None; Radha Ayyagari, None; Jerome Rotter, 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)
  • Footnotes
    Support  National Eye Institute: EY023704, P30EY022589, EY110008, EY019869, EY021818 National Institutes of Health: R01 DK087914, R01 DK066358, R01 DK053591, U01 DK105556, R01 HL56266, R01 DK070941, DRC DK063491, and CTSI UL1TR001881
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 5137. doi:https://doi.org/
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    • Get Citation

      Kent Taylor, Xiuqing Guo, Linda M Zangwill, Jeffrey M Liebmann, Christopher A Girkin, Robert M Feldman, Harvey Dubiner, Nicholette D Palmer, Barry I Freedman, Donald W Bowden, Maggie CY Ng, Yii-Der Ida Chen, Radha Ayyagari, Jerome I Rotter, Robert N Weinreb; Genomic Architecture of POAG in Individuals of African Descent
      --African Descent & Glaucoma Evaluation Study (ADAGESIII)--. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5137. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : To investigate the genomic architecture of primary open angle glaucoma (POAG) in individuals of African Descent (AD).

Methods : 1875 POAG cases and 1709 controls, all self-identified as having African descent (AD) from ADAGESIII and Wake Forest University were genotyped with the Illumina MegaChip. Genotype data were imputed to the 1000 Genomes dataset. The association of SNPs with POAG and advanced POAG was tested using a linear mixed model that corrects for sample relatedness and population stratification. Genetic risk scores were calculated using two methods and tested by plotting the Area Under the Receiver Operator Characteristics Curve (AUC).

Results : After quality measures, genotype data for 870,067 autosomal SNPs with a minor allele frequency >0.005 for cases and controls were generated. After imputation to the 1000 Genomes dataset, 17,794,691 SNPs met quality of imputation r2>0.7 and control minor allele frequency > 0.005. Association of a novel locus, ENO4, was observed at SNP rs85815146 (advanced POAG, effect 0.36, p<3x10-8). In addition to association with the 9p21 signal previously observed in individuals of European descent (ED) (rs2383204; p<2x10-5), an independent, novel, AD 9p21 signal was observed (rs79721419; p<6x10-5). AD specific signals were also observed in the FNDC3B (rs111698934, p<6x10-6) and the GAS7 (rs8080535, p<1x10-4) loci. An AUC of 0.62 was observed with a score composed of the 11 SNPs in the previously reported ED POAG loci. By using a penalized matrix decomposition, risk scores with AUC = 0.74 and AUC = 0.94 were obtained by adding 50 and 400 AD SNPs respectively.

Conclusions : These observations support the concept that GWAS in African-Americans will contribute to the study of the genomics of POAG in all populations by providing novel loci (ENO4), by providing novel signals in prior loci (9p21), and by advancing the fine-mapping of regions due to shorter linkage disequilibrium (FNDC3B, GAS7). The observed increase in AUC observed by adding AD SNPs supports the concepts that a great deal of AD specific genomic information remains in these data and that further collaborations are warranted for its identification.

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

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