[Skip to Navigation]
Brief Report
July 15, 2021

Association of Monogenic and Polygenic Risk With the Prevalence of Open-Angle Glaucoma

Author Affiliations
  • 1Department of Ophthalmology, Flinders University, Bedford Park, Australia
  • 2Garvan Institute of Medical Research, Darlinghurst, Australia
  • 3QIMR Berghofer Medical Research Institute, Brisbane, Australia
  • 4Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia
  • 5Lions Eye Institute, Centre for Ophthalmology and Vision Sciences, University of Western Australia, Perth, Australia
  • 6Centre for Eye Research Australia, University of Melbourne, Melbourne, Australia
JAMA Ophthalmol. 2021;139(9):1023-1028. doi:10.1001/jamaophthalmol.2021.2440
Key Points

Question  What is the association of monogenic and polygenic variants with glaucoma risk?

Findings  In this cross-sectional study of 2507 individuals with open-angle glaucoma, high polygenic risk was associated with risk of developing glaucoma comparable with the risk associated with the most common single-gene pathogenic variant, but was more than 15 times more prevalent in the general population than this single-gene variant.

Meaning  In this study, polygenic variants were associated with a comparable risk of developing glaucoma as some monogenic risk variants and were more prevalent in the general population.


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.

Add or change institution