The intraocular pressure (IOP) polygenic risk score (PRS) can identify which patients will benefit most from intensive treatment to lower IOP and manage these patients’ intraocular pressure risk. glaucomaAccording to a study published in JAMA Ophthalmology.¹ Vertical cup-to-disc ratio (VCDR) PRS can also be used to determine glaucoma risk even in patients with normal IOP.

Glaucoma is an eye condition that can lead to vision loss and blindness; The most common type of glaucoma is primary open angle glaucoma (POAG).² The global prevalence rate is 2.4%. IOP and VCDR are two of the risk factors for POAG and are necessary to try to diagnose the condition early to prevent the worst outcomes in patients. Because IOP and VCDR are hereditary, PRS may be useful in identifying individuals most at risk. This study aimed to evaluate how PRS can help identify patients at highest risk based on OP and VCDR scores.

This study used multiple cohorts from previous studies, including the Canadian Longitudinal Study of Aging (CLSA), the Busselton Healthy Aging Study (BHAS), and the UK Biobank. CLSA included data collected from Canadians aged 45 to 85 between 2010 and 2015. Corneal compensating IOP measurements were calculated for baseline and follow-up in this data set. Participants without IOP measurement were excluded from the study.

A PRS can estimate the incidence of glaucoma in individuals and allow for more targeted treatment for these patients. Image credit: Alessandro Grandini – Stock.adobe.com

BHAS included participants from Busselton, Western Australia, with data collected from individuals aged 46 to 64 between 2010 and 2015. There were 4839 individuals with IOP PRS verification and 1588 individuals with VCDR PRS verification. The UK Biobank was also used for this study, collecting data on individuals aged 40 to 69 living in the UK from 2006 to 2010. Patients of African, East Asian, and South Asian descent were included.

There were 5890 samples from CLSA used to evaluate the relationship between VCDR and IOP and PRS. The researchers found that the base model accounted for 3.8% (95% CI, 2.9-4.8) of the variance in unadjusted VCDR and 2.5% (95% CI, 1.8-3) of the variance in adjusted VCDR. ,4) found what he explained. The new PRS accounted for 22.0% (95% CI, 20.1-23.9) of the variance in phenotypes in the adjusted VCDR and 21.9% (95% CI, 21.9%) in the unadjusted VCDR, both in the CLSA data set. 20.1-23.8) was able to explain. The variance in IOP phenotypes could also be explained by 12.9% (95% CI, 11.3-14.6). A total of 3.1% (95% CI, 2.3–4.0) of the variance in phenotypes was explained in the base model.

There were 1588 samples in the BHAS dataset, which were used to perform PRS validation. Variance with 0.98% (95% CI, 0.3-2.2) of adjusted VCDR and 0.79% (95% CI, 0.2-1.9) of unadjusted VCDR announced. PRS was able to explain 19.7% and 18.3% of the variance in adjusted and unadjusted VCDR, respectively. IOP PRS was able to explain 9.6% of the variance in the phenotype.

Using the UK Biobank, VCDR PRS variance explained 5.2%, 12.1%, and 14.3% for African, East Asian, and South Asian populations, respectively; IOP PRS variance explained 2.3%, 3.2%, and 7.5% in the same populations.

This study had some limitations. PRS is derived from samples obtained from individuals of European ancestry and is therefore less predictive in individuals of non-European ancestry. Future studies in African individuals may be needed in this area to elucidate IOP differences in this subgroup. These results also did not impact clinically meaningful outcomes for glaucoma.

The researchers concluded that a new PRS, based on the latest genome-wide association studies, was able to more accurately predict VCDR or IOP compared to previous data. This can be used to help predict glaucoma in these patients.

References

1. He W, Lee SSY, Diaz Torres S, et al. Predictive power of polygenic risk scores for intraocular pressure or vertical cup-to-disc ratio. JAMA Ophthalmol. Published online November 21, 2024. doi:10.1001/jamaophthalmol.2024.4856
2. Glaucoma. National Eye Institute. Updated on November 15, 2023. Access date: 21 November 2024.