Recall by polygenic risk score in two biobanks supports a genomic approach for glaucoma detection

Glaucoma is a highly heritable optic neuropathy and a leading cause of blindness; yet, glaucoma screening is challenging due to the time-consuming clinical methods required for disease identification and the imperfect accuracy of screening tests. We used genome-wide association study results to calculate a primary open angle glaucoma (POAG) polygenic risk score (PRS) for Mount Sinai BioMe and Mass General Brigham Biobank participants. Glaucoma prevalence for recalled individuals in the top and bottom PRS decile groups were compared after standardized clinical examinations masked to PRS status. The top PRS decile group had an overall glaucoma prevalence of 18.8% and was 6.7 times (Odds Ratio 95% confidence interval: 3.1 – 14.3) more likely to be diagnosed with glaucoma compared to the bottom PRS decile group. Notably, 47.1% of identified glaucoma cases in the high-risk group were previously undiagnosed. These results support using PRS testing to detect glaucoma and to identify patients for increased surveillance or preventative treatment.