eCite Digital Repository

Association of monogenic and polygenic risk with the prevalence of open-angle glaucoma


Siggs, OM and Han, X and Qassim, A and Souzeau, E and Kuruvilla, S and Marshall, HN and Mullany, S and Mackey, DA and Hewitt, AW and Gharahkhani, P and MacGregor, S and Craig, JE, Association of monogenic and polygenic risk with the prevalence of open-angle glaucoma, JAMA Ophthalmology, 139, (9) pp. 1023-1028. ISSN 2168-6165 (2021) [Refereed Article]

Copyright Statement

Copyright 2021 American Medical Association

DOI: doi:10.1001/jamaophthalmol.2021.2440


Importance: Early diagnosis of open-angle glaucoma can lead to vision-saving treatment, and genetic variation is an increasingly powerful indicator in disease risk stratification.

Objective: To compare polygenic and monogenic variants in risk of glaucoma.

Design, setting, and participants: Clinical and genetic data were obtained for 2507 individuals from the Australian and New Zealand Registry of Advanced Glaucoma (ANZRAG) and 411 337 individuals in cross-sectional cohort studies including individuals of European ancestry in the UK Biobank. Recruitment to the UK Biobank occurred between 2006 and 2010, and data analysis occurred between September 2019 and August 2020.

Main outcomes and measures: Association of monogenic and polygenic variants with glaucoma risk.

Results: Individuals at high polygenic risk, defined as those in the top 5% of an unselected population, had a glaucoma risk (odds ratio [OR], 2.77; 95% CI, 2.58-2.98) comparable with the risk among individuals heterozygous for the MYOC p.Gln368Ter variant (OR 4.19; 95% CI, 3.25-5.31), which is the most common single-gene variant known to cause primary open-angle glaucoma. High polygenic risk was more than 6 times more common than MYOC p.Gln368Ter heterozygosity in ANZRAG (15.7% vs 2.6%) and more than 15 times more common in the general population (5.0% vs 0.32%). Within ANZRAG, high polygenic risk was associated with a mean (SD) age at glaucoma diagnosis that did not differ from the age at glaucoma diagnosis among individuals heterozygous for MYOC p.Gln368Ter (57.2 [14.2] vs 54.8 [13.6] years; P > .99).

Conclusions and relevance: Monogenic and high polygenic risk were each associated with a more than 2.5-fold increased odds of developing glaucoma and an equivalent mean age at glaucoma diagnosis, with high polygenic risk more than 15 times more common in the general population.

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:Diagnosis of human diseases and conditions
UTAS Author:Mackey, DA (Professor David Mackey)
UTAS Author:Hewitt, AW (Professor Alex Hewitt)
ID Code:147323
Year Published:2021
Web of Science® Times Cited:7
Deposited By:Menzies Institute for Medical Research
Deposited On:2021-10-26
Last Modified:2021-11-04

Repository Staff Only: item control page