Polygenic risk scores (PRS) have been developed for a wide range of complex traits in recent years. PRS vary across diseases in terms of their accuracy and clinical relevance. We have developed a powerful PRS for the eye disease glaucoma, with these PRS results among the first to be returned to patients in Australia. However, barriers remain preventing more widespread use of PRS, including improved evidence for the practical utility of PRS in preventing morbidity as well as key equity issues.
We are commencing a randomized trial embedded within our large scale study, Genetics of Glaucoma. The trial will determine if PRS-based risk stratification can assist with identifying and appropriately monitoring and treating those at highest risk of glaucoma. We will describe pilot data from the trial showing that our glaucoma PRS predicts incident glaucoma in Genetics of Glaucoma participants followed over time since 2020. When complete, the trial is anticipated to provide evidence to support the use of PRS for determining an appropriate screening interval for people at high risk of glaucoma. Given glaucoma is frequently diagnosed too late (50% of cases in Australia are undiagnosed) this approach may assist with timely diagnosis and prevent blindness.
We will discuss barriers to return of PRS results to patients, in the trial setting as well as more generally in the community. One key issue is how to account for the fact that glaucoma PRS have varying performance across different ancestry groups. We will discuss approaches to deal with this, and describe methods for adjusting for ancestry, including for people from admixed genetic backgrounds.