{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T10:13:42Z","timestamp":1785233622370,"version":"3.55.0"},"reference-count":55,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2024,5,17]],"date-time":"2024-05-17T00:00:00Z","timestamp":1715904000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["K01HL148639-04)"],"award-info":[{"award-number":["K01HL148639-04)"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIH UC San Diego Future Faculty of Cardiovascular Sciences Small Research Project Grant"},{"DOI":"10.13039\/100019607","name":"Stanford Cardiovascular Institute, School of Medicine, Stanford University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100019607","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>We have previously shown that polygenic risk scores (PRS) can improve risk stratification of peripheral artery disease (PAD) in a large, retrospective cohort. Here, we evaluate the potential of PRS in improving the detection of PAD and prediction of major adverse cardiovascular and cerebrovascular events (MACCE) and adverse events (AE) in an institutional patient cohort. We created a cohort of 278 patients (52 cases and 226 controls) and fit a PAD-specific PRS based on the weighted sum of risk alleles. We built traditional clinical risk models and machine learning (ML) models using clinical and genetic variables to detect PAD, MACCE, and AE. The models\u2019 performances were measured using the area under the curve (AUC), net reclassification index (NRI), integrated discrimination improvement (IDI), and Brier score. We also evaluated the clinical utility of our PAD model using decision curve analysis (DCA). We found a modest, but not statistically significant improvement in the PAD detection model\u2019s performance with the inclusion of PRS from 0.902 (95% CI: 0.846\u20130.957) (clinical variables only) to 0.909 (95% CI: 0.856\u20130.961) (clinical variables with PRS). The PRS inclusion significantly improved risk re-classification of PAD with an NRI of 0.07 (95% CI: 0.002\u20130.137), <jats:italic>p<\/jats:italic> = 0.04. For our ML model predicting MACCE, the addition of PRS did not significantly improve the AUC, however, NRI analysis demonstrated significant improvement in risk re-classification (<jats:italic>p<\/jats:italic> = 2e-05). Decision curve analysis showed higher net benefit of our combined PRS-clinical model across all thresholds of PAD detection. Including PRS to a clinical PAD-risk model was associated with improvement in risk stratification and clinical utility, although we did not see a significant change in AUC. This result underscores the potential clinical utility of incorporating PRS data into clinical risk models for prevalent PAD and the need for use of evaluation metrics that can discern the clinical impact of using new biomarkers in smaller populations.<\/jats:p>","DOI":"10.1371\/journal.pone.0303610","type":"journal-article","created":{"date-parts":[[2024,5,17]],"date-time":"2024-05-17T18:19:51Z","timestamp":1715969991000},"page":"e0303610","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":19,"title":["Clinical use of polygenic risk scores for detection of peripheral artery disease and cardiovascular events"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0659-831X","authenticated-orcid":true,"given":"Jesutofunmi 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