Skip to main content
Journal cover image

Genetic Architecture of Primary Open-Angle Glaucoma in Individuals of African Descent: The African Descent and Glaucoma Evaluation Study III.

Publication ,  Journal Article
Taylor, KD; Guo, X; Zangwill, LM; Liebmann, JM; Girkin, CA; Feldman, RM; Dubiner, H; Hai, Y; Samuels, BC; Panarelli, JF; Mitchell, JP; Das, SK ...
Published in: Ophthalmology
January 2019

PURPOSE: To find genetic contributions to glaucoma in African Americans. DESIGN: Cross-sectional, case-control study. PARTICIPANTS: One thousand eight hundred seventy-five primary open-angle glaucoma (POAG) patients and 1709 controls, self-identified as being of African descent (AD), from the African Descent and Glaucoma Evaluation Study (ADAGES) III and Wake Forest School of Medicine. METHODS: MegaChip genotypes were imputed to Thousand Genomes data. Association of single nucleotide polymorphisms (SNPs) with POAG and advanced POAG was tested by linear mixed model correcting for relatedness and population stratification. Genetic risk scores were tested by receiver operator characteristic curves (ROC-AUCs). MAIN OUTCOME MEASURES: Primary open-angle glaucoma defined by visual field loss without other nonocular conditions (n = 1875). Advanced POAG was defined by age-based mean deviation of visual field (n = 946). RESULTS: Eighteen million two hundred eighty-one thousand nine hundred twenty SNPs met imputation quality of r2 > 0.7 and minor allele frequency > 0.005. Association of a novel locus, EN04, was observed for advanced POAG (rs185815146 β, 0.36; standard error, 0.065; P < 3×10-8). For POAG, an AD signal was observed at the 9p21 European descent (ED) POAG signal (rs79721419; P < 6.5×10-5) independent of the previously observed 9p21 ED signal (rs2383204; P < 2.3×10-5) by conditional analyses. An association with POAG in FNDC3B (rs111698934; P < 3.9×10-5) was observed, not in linkage disequilibrium (LD) with the previously reported ED SNP. Additional previously identified loci associated with POAG in persons of AD were: 8q22, AFAP1, and TMC01. An AUC of 0.62 was observed with an unweighted genetic risk score comprising 11 SNPs in candidate genes. Two additional risk scores were studied by using a penalized matrix decomposition with cross-validation; risk scores of 50 and 400 SNPs were identified with ROC of AUC = 0.74 and AUC = 0.94, respectively. CONCLUSIONS: A novel association with advanced POAG in the EN04 locus was identified putatively in persons of AD. In addition to this finding, this genome-wide association study in POAG patients of AD contributes to POAG genetics by identification of novel signals in prior loci (9p21), as well as advancing the fine mapping of regions because of shorter average LD (FNDC3B). Although not useful without confirmation and clinical trials, the use of genetic risk scores demonstrated that considerable AD-specific genetic information remains in these data.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Ophthalmology

DOI

EISSN

1549-4713

Publication Date

January 2019

Volume

126

Issue

1

Start / End Page

38 / 48

Location

United States

Related Subject Headings

  • ROC Curve
  • Polymorphism, Single Nucleotide
  • Phosphopyruvate Hydratase
  • Ophthalmology & Optometry
  • Middle Aged
  • Male
  • Intraocular Pressure
  • Humans
  • Glaucoma, Open-Angle
  • Genotype
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Taylor, K. D., Guo, X., Zangwill, L. M., Liebmann, J. M., Girkin, C. A., Feldman, R. M., … African Descent and Glaucoma Evaluation Study III Genomics Study Group, . (2019). Genetic Architecture of Primary Open-Angle Glaucoma in Individuals of African Descent: The African Descent and Glaucoma Evaluation Study III. Ophthalmology, 126(1), 38–48. https://doi.org/10.1016/j.ophtha.2018.10.031
Taylor, Kent D., Xiuqing Guo, Linda M. Zangwill, Jeffrey M. Liebmann, Christopher A. Girkin, Robert M. Feldman, Harvey Dubiner, et al. “Genetic Architecture of Primary Open-Angle Glaucoma in Individuals of African Descent: The African Descent and Glaucoma Evaluation Study III.Ophthalmology 126, no. 1 (January 2019): 38–48. https://doi.org/10.1016/j.ophtha.2018.10.031.
Taylor KD, Guo X, Zangwill LM, Liebmann JM, Girkin CA, Feldman RM, et al. Genetic Architecture of Primary Open-Angle Glaucoma in Individuals of African Descent: The African Descent and Glaucoma Evaluation Study III. Ophthalmology. 2019 Jan;126(1):38–48.
Taylor, Kent D., et al. “Genetic Architecture of Primary Open-Angle Glaucoma in Individuals of African Descent: The African Descent and Glaucoma Evaluation Study III.Ophthalmology, vol. 126, no. 1, Jan. 2019, pp. 38–48. Pubmed, doi:10.1016/j.ophtha.2018.10.031.
Taylor KD, Guo X, Zangwill LM, Liebmann JM, Girkin CA, Feldman RM, Dubiner H, Hai Y, Samuels BC, Panarelli JF, Mitchell JP, Al-Aswad LA, Park SC, Tello C, Cotliar J, Bansal R, Sidoti PA, Cioffi GA, Blumberg D, Ritch R, Bell NP, Blieden LS, Davis G, Medeiros FA, Das SK, Divers J, Langefeld CD, Palmer ND, Freedman BI, Bowden DW, Ng MCY, Ida Chen Y-D, Ayyagari R, Rotter JI, Weinreb RN, African Descent and Glaucoma Evaluation Study III Genomics Study Group. Genetic Architecture of Primary Open-Angle Glaucoma in Individuals of African Descent: The African Descent and Glaucoma Evaluation Study III. Ophthalmology. 2019 Jan;126(1):38–48.
Journal cover image

Published In

Ophthalmology

DOI

EISSN

1549-4713

Publication Date

January 2019

Volume

126

Issue

1

Start / End Page

38 / 48

Location

United States

Related Subject Headings

  • ROC Curve
  • Polymorphism, Single Nucleotide
  • Phosphopyruvate Hydratase
  • Ophthalmology & Optometry
  • Middle Aged
  • Male
  • Intraocular Pressure
  • Humans
  • Glaucoma, Open-Angle
  • Genotype