June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
Genome-wide Association Study Finds Multiple Loci Associated with Intraocular Pressure In HS Rats
Author Affiliations & Notes
  • Samuel Fowler
    Department of Ophthalmology, The University of Tennessee Health Science Center, Memphis, Tennessee, United States
  • Tengfei Wang
    Department of Pharmacology, Addiction Science, and Toxicology, The University of Tennessee Health Science Center, Memphis, Tennessee, United States
  • TJ Hollingsworth
    Department of Ophthalmology, The University of Tennessee Health Science Center, Memphis, Tennessee, United States
  • Angel Garcia Martinez
    Department of Pharmacology, Addiction Science, and Toxicology, The University of Tennessee Health Science Center, Memphis, Tennessee, United States
  • Jie Ni
    Department of Pharmacology, Addiction Science, and Toxicology, The University of Tennessee Health Science Center, Memphis, Tennessee, United States
  • Dan Munro
    Department of Psychiatry, and Institute for Genomic Medicine, University of California San Diego, La Jolla, California, United States
  • Hao Chen
    Department of Pharmacology, Addiction Science, and Toxicology, The University of Tennessee Health Science Center, Memphis, Tennessee, United States
  • Abraham A Palmer
    Department of Psychiatry, and Institute for Genomic Medicine, University of California San Diego, La Jolla, California, United States
  • Oksana Polesskaya
    Department of Psychiatry, and Institute for Genomic Medicine, University of California San Diego, La Jolla, California, United States
  • Monica M Jablonski
    Department of Ophthalmology, The University of Tennessee Health Science Center, Memphis, Tennessee, United States
  • Footnotes
    Commercial Relationships   Samuel Fowler, None; Tengfei Wang, None; TJ Hollingsworth, None; Angel Martinez, None; Jie Ni, None; Dan Munro, None; Hao Chen, None; Abraham A Palmer, None; Oksana Polesskaya, None; Monica Jablonski, None
  • Footnotes
    Support   NIH Grant EY021200 and Research to Prevent Blindness Challenge Grant
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 1516. doi:
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      Samuel Fowler, Tengfei Wang, TJ Hollingsworth, Angel Garcia Martinez, Jie Ni, Dan Munro, Hao Chen, Abraham A Palmer, Oksana Polesskaya, Monica M Jablonski; Genome-wide Association Study Finds Multiple Loci Associated with Intraocular Pressure In HS Rats. Invest. Ophthalmol. Vis. Sci. 2021;62(8):1516.

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

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Abstract

Purpose : Elevated intraocular pressure (IOP) is influenced by environmental and genetic factors. It is associated with multiple disease processes with primary open angle glaucoma (POAG) being the most prevalent. Due to its complex, multifactorial nature, genetic predisposition is not completely understood, and a standardized animal model has yet to be developed for POAG. Heterogenous stock (HS) outbred rats is a multigenerational outbred population derived from eight fully sequenced founder strains. This population is ideal for genome-wide association studies (GWAS) due to most genetic variants being common, access to a large collection of tissue samples, and the large allelic effect size compared to human studies. The purpose of this study was to use HS rats to identify genetic loci underlying elevated IOP.

Methods : Both male and female HS rats (N=1812) were used in the study with genotyping by sequencing conducted on all subjects. We mapped quantitative trait loci (QTLs) for IOP phenotypes and SNP heritabilities were estimated. We used permutation to determine the threshold for significance using an empirical p value of 0.05. Linear mixed model was used to control for the complex family relationships of the HS rats.

Results : GWAS identified three genome wide significant loci for elevated IOP located on chromosomes 1, 5, and 16. The QTLs contained 18 genes in total. Only one of these genes has been previously associated with human POAG.

Conclusions : This study highlights the efficacy of HS rats for investigating the genetics of elevated IOP and identifying potential candidate genes for future functional testing. GWAS is a powerful method for identifying genome regions which harbor variants responsible for the variation in quantitative traits, such as IOP. The identification of three independent QTLs in a relatively small sample size is promising for continued future findings as the sample population grows. Additional studies are ongoing to narrow the list of candidate genes in these intervals.

This is a 2021 ARVO Annual Meeting abstract.

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