June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
Investigation of the use of drusen as a biomarker for age-related macular degeneration reveals shared genetic risk in the Amish
Author Affiliations & Notes
  • Michael David Osterman
    Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, Ohio, United States
    Cleveland Institute for Computational Biology, Case Western Reserve University, Cleveland, Ohio, United States
  • Yeunjoo E Song
    Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, Ohio, United States
    Cleveland Institute for Computational Biology, Case Western Reserve University, Cleveland, Ohio, United States
  • Muneeswar Nittala
    Doheny Imaging Reading Center, Doheny Eye Institute, Los Angeles, California, United States
  • Srinivas R Sadda
    Doheny Imaging Reading Center, Doheny Eye Institute, Los Angeles, California, United States
  • William K Scott
    Hussman Institute for Human Genomics, University of Miami, Coral Gables, Florida, United States
  • Dwight Stambolian
    Ophthalmology and Genetics, University of Pennsylvania, Philadelphia, Pennsylvania, United States
  • Margaret A Pericak-Vance
    Hussman Institute for Human Genomics, University of Miami, Coral Gables, Florida, United States
  • Jonathan L Haines
    Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, Ohio, United States
    Cleveland Institute for Computational Biology, Case Western Reserve University, Cleveland, Ohio, United States
  • Footnotes
    Commercial Relationships   Michael Osterman, None; Yeunjoo Song, None; Muneeswar Nittala, None; Srinivas Sadda, 4DMT (C), Allergan (C), Amgen (C), Bayer (C), Carl Zeiss Meditec (F), Centervue (C), Centervue (F), Genentech/Roche (C), Heidelberg (C), Heidelberg Engineering (F), Nidek (F), Novartis (C), Optos (C), Optos (F), Oxurion (C), Regeneron (C), Topcon (F); William Scott, None; Dwight Stambolian, None; Margaret Pericak-Vance, None; Jonathan Haines, None
  • Footnotes
    Support  NIH Grant EY023164, EY022310, EY012118
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 170. doi:
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      Michael David Osterman, Yeunjoo E Song, Muneeswar Nittala, Srinivas R Sadda, William K Scott, Dwight Stambolian, Margaret A Pericak-Vance, Jonathan L Haines; Investigation of the use of drusen as a biomarker for age-related macular degeneration reveals shared genetic risk in the Amish. Invest. Ophthalmol. Vis. Sci. 2021;62(8):170.

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Abstract

Purpose : Age-related macular degeneration (AMD) is the leading cause of vision loss nationwide and accounts for 8.7% of blindness. Detailed GA and drusen measurements may be promising biomarkers for staging and monitoring of AMD. However, the genetic relationship between these traits and AMD is not fully understood. Here, we investigate the genetics of quantitative measures of drusen and GA in an Amish population using genetic risk scores (GRSs) derived from a previous large AMD genome-wide association study (GWAS).

Methods : We performed chip genotyping using an Illumina Multi-Ethnic Genotyping Array with custom content. GA and drusen measures were obtained from macular optical coherence tomography (OCT) volume scans. 1,117 Amish adults with a family history of AMD from Ohio, Pennsylvania, and Indiana were included in the analyses after quality control and assurance. GRS were constructed using summary statistics of genome-wide significant SNPs for AMD from Fritsche et al. (2016). We tested the impact of the GRS for both the presence/absence of GA and drusen and, for those with GA and/or drusen, the impact on the measures. Traits included geographic atrophy, drusen area, and drusen volume within 3 and 5mm circles centered on the fovea. Logistic regression models were used to test the added utility in predicting the presence each of these drusen traits beyond a basic covariate-only model including age, sex, and smoking status. Similarly, linear models were constructed to investigate prediction of the quantitative measures of each of these traits by using the same predictors on subsets of individuals with presence of each of the traits.

Results : Results indicated a small, but statistically significant (p < 0.05), effect of the GRS to improve model performance for presence of each of the five traits. Area under curve (AUC) for drusen area and volume in a 3mm circle improved from 0.797 and 0.831 to 0.825 and 0.864, respectively, by adding the GRS to a covariate-only model. Further, it had a significant effect in improving prediction of the quantitative measures of drusen area and volume.

Conclusions : These results suggest that drusen development and AMD share underlying risk loci, helping to elucidate the relationship between drusen and AMD, potentially allowing for future use of drusen traits as a biomarker.

This is a 2021 ARVO Annual Meeting abstract.

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