{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T13:01:56Z","timestamp":1790254916447,"version":"4.1.0"},"posted":{"date-parts":[[2025,9,29]]},"group-title":"Ophthalmology","reference-count":87,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T00:00:00Z","timestamp":1759104000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["R01EY023557"],"award-info":[{"award-number":["R01EY023557"]}],"id":[{"id":"https:\/\/ror.org\/03wkg3b53","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Vision Research Core Grant","award":["2P30EY001583-51"],"award-info":[{"award-number":["2P30EY001583-51"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,21]]},"abstract":"<jats:title>SUMMARY<\/jats:title>\n                <jats:p>Primary open-angle glaucoma (POAG) disproportionately affects individuals of African ancestry, for whom risk prediction tools remain limited. We evaluated four polygenic risk scores (PGS), two genome-wide and two curated, weighted by African ancestry effect sizes. Used alone, the scores showed modest discrimination. Age and sex were strongly predictive; adding PGS616 reached a cross-validated AUC of 0.713 in the training cohort (N = 271), comparable to the demographic model. In the Penn Medicine BioBank (N = 9,084) the model reached AUC = 0.727, similar to 0.729 for age and sex alone, with comparable case detection at fixed specificity. In a suspect cohort (N = 1,013), predicted risk tracked cup-to-disc ratio and nerve fiber layer thinning, an association explained by age and sex. These results establish a demographic benchmark for evaluating ancestry-matched PGS in POAG.<\/jats:p>\n                <jats:sec>\n                  <jats:title>HIGHLIGHTS<\/jats:title>\n                  <jats:list list-type=\"bullet\">\n                    <jats:list-item>\n                      <jats:p>Age and sex alone predict POAG well in a high-risk African ancestry cohort<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Four ancestry-matched PGS show modest standalone discrimination in this cohort<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Adding PGS616 to age and sex gives comparable AUC in both cohorts (primary MLP)<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Predicted risk tracks optic nerve damage in suspects, driven by age and sex<\/jats:p>\n                    <\/jats:list-item>\n                  <\/jats:list>\n                <\/jats:sec>","DOI":"10.1101\/2025.09.27.25336797","type":"posted-content","created":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T23:25:23Z","timestamp":1759188323000},"source":"Crossref","is-referenced-by-count":0,"title":["Multimodal Prediction of Primary Open-Angle Glaucoma Using Polygenic Risk Scores and Clinical Features in a High-Risk African Ancestry Cohort"],"prefix":"10.64898","author":[{"given":"Yan","family":"Zhu","sequence":"first","affiliation":[{"name":"Center for Genetics of Complex Disease, Department of Ophthalmology, University of Pennsylvania, Philadelphia, PA 19104, US"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3770-2299","authenticated-orcid":false,"given":"Aude Benigne","family":"Ikuzwe Sindikubwabo","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Pennsylvania, 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