Editors Selection IGR 21-4

Risk Factors: Predicting the Genetic Risk of IOP Spikes by a Genome-Wide Score

Janey Wiggs

Comment by Janey Wiggs on:

91808 A Polygenic Risk Score Predicts Intraocular Pressure Readings Outside Office Hours and Early Morning Spikes as Measured by Home Tonometry, Qassim A; Mullany S; Awadalla MS et al., Ophthalmology. Glaucoma, 2020; 0:

See also comment(s) by Anthony Khawaja & Kelsey Stuart

Find related abstracts

Polygenic risk scores (PRS) are a recently developed genomic tool that determines personal disease risk by aggregating individual genetic effects to create an overall score based on the total number of risk alleles. PRSs have been used to identify individuals at high risk for inherited common diseases including coronary artery disease, obesity, atrial fibrillation, type II diabetes, as well as primary open-angle glaucoma (POAG) and glaucoma-related traits including IOP. Interestingly, POAG and IOP PRSs are associated with important disease features such as age of diagnosis, need for surgical intervention and penetrance of the earlyonset glaucoma gene MYOC.1,2 In this study, Qassim et al. used a validated PRS comprised of genetic risk factors derived from an IOP genome-wide association study (GWAS) to investigate the relationship between PRS quintiles and IOP levels measured using Icare HOME tonometry. Two hundred thirty-nine individuals had IOP measurements four times daily for five days and reliable measurements were obtained in 176 of these people. People in the highest PRS quintile had a mean increase in IOP (2.7 mmHg, 95%CI 0.61-4.7, P = 0.013) outside of office hours compared with those in the lowest PRS quintile. In particular, people with the highest PRS score had increased early morning IOP (4.3 mmHg 95% CI 1.4-7.3; P = 0.005) and people in the highest PRS quintile were 5.4 times more likely to shown early morning IOP spikes compared to the lowest quintile (odds ratio 95% CI, 1.3-23.6; P = 0.023). These results suggest that people with higher genetic risk as defined by an IOP PRS are more likely to have higher IOP pressure measurements outside of clinic hours and especially to have higher IOP in the early morning including IOP spikes. This information could inform therapeutic decisions and may be particularly relevant in people who show evidence of progression despite stable IOP measured in the clinic. There are limitations to the current study including a relatively small number of people studied, however further study and confirmation of these intriguing results is warranted.


  1. Craig JE, et al. Multitrait analysis of glaucoma identifies new risk loci and enables polygenic prediction of disease susceptibility and progression. Nat Genet. 2020;52:160-166.
  2. Zebardast N, et al. Characteristics of Gln368Ter Myocilin Variant and Influence of Polygenic Risk on Glaucoma Penetrance in the UK Biobank. Ophthalmology. 2021; doi:10.1016/j.ophtha.2021.03.007.

Issue 21-4

Change Issue