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An intraocular pressure polygenic risk score stratifies multiple primary open-angle glaucoma parameters including treatment intensity


Qassim, A and Souzeau, E and Siggs, OM and Hassall, MM and Han, X and Griffiths, HL and Frost, NA and Vallabh, NA and Kirwan, JF and Menon, G and Cree, AJ and Galanopoulos, A and Agar, A and Healey, PR and Graham, SL and Landers, J and Casson, RJ and Gharahkhani, P and Willoughby, CE and Hewitt, AW and Lotery, AJ and MacGregor, S and Craig, JE, An intraocular pressure polygenic risk score stratifies multiple primary open-angle glaucoma parameters including treatment intensity, Ophthalmology, 127, (7) pp. 901-907. ISSN 0161-6420 (2020) [Refereed Article]

Copyright Statement

Copyright 2020 by the American Academy of Ophthalmology.

DOI: doi:10.1016/j.ophtha.2019.12.025


Purpose: To examine the combined effects of common genetic variants associated with intraocular pressure (IOP) on primary open-angle glaucoma (POAG) phenotype using a polygenic risk score (PRS) stratification.

Design: Cross-sectional study.

Participants: For the primary analysis, we examined the glaucoma phenotype of 2154 POAG patients enrolled in the Australian and New Zealand Registry of Advanced Glaucoma, including patients recruited from the United Kingdom. For replication, we examined an independent cohort of 624 early POAG patients.

Methods: Using IOP genome-wide association study summary statistics, we developed a PRS derived solely from IOP-associated variants and stratified POAG patients into 3 risk tiers. The lowest and highest quintiles of the score were set as the low- and high-risk groups, respectively, and the other quintiles were set as the intermediate risk group.

Main outcome measures: Clinical glaucoma phenotype including maximum recorded IOP, age at diagnosis, number of family members affected by glaucoma, cup-to-disc ratio, visual field mean deviation, and treatment intensity.

Results: A dose-response relationship was found between the IOP PRS and the maximum recorded IOP, with the high genetic risk group having a higher maximum IOP by 1.7 mmHg (standard deviation [SD], 0.62 mmHg) than the low genetic risk group (P = 0.006). Compared with the low genetic risk group, the high genetic risk group had a younger age of diagnosis by 3.7 years (SD, 1.0 years; P < 0.001), more family members affected by 0.46 members (SD, 0.11 members; P < 0.001), and higher rates of incisional surgery (odds ratio, 1.5; 95% confidence interval, 1.1-2.0; P = 0.007). No statistically significant difference was found in mean deviation. We further replicated the maximum IOP, number of family members affected by glaucoma, and treatment intensity (number of medications) results in the early POAG cohort (P ≤ 0.01).

Conclusions: The IOP PRS was correlated positively with maximum IOP, disease severity, need for surgery, and number of affected family members. Genes acting via IOP-mediated pathways, when considered in aggregate, have clinically important and reproducible implications for glaucoma patients and their close family members.

Item Details

Item Type:Refereed Article
Research Division:Biomedical and Clinical Sciences
Research Group:Ophthalmology and optometry
Research Field:Ophthalmology
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Hewitt, AW (Professor Alex Hewitt)
ID Code:139730
Year Published:2020
Web of Science® Times Cited:6
Deposited By:Menzies Institute for Medical Research
Deposited On:2020-06-30
Last Modified:2020-07-16

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