{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T18:28:27Z","timestamp":1787077707661,"version":"build-2736575974"},"reference-count":71,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Genomic and Precision Medicine"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Performance and transferability of contemporary polygenic risk scores (PRS) for atherosclerotic cardiovascular disease phenotypes may vary across PRS methods, training data, and trait ascertainment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>\n                      We aimed to investigate the performance and transferability of contemporary PRS for atherosclerotic cardiovascular disease subtypes: coronary heart disease (CHD), abdominal aortic aneurysm (AAA), ischemic stroke (IS), and peripheral artery disease (PAD), using the\n                      <jats:italic toggle=\"yes\">All of Us<\/jats:italic>\n                      Workbench, which consists of a large, diverse cohort with whole-genome sequence data. We also developed and evaluated a multi-trait PRS for each subtype. Performance of PRS for 4 atherosclerotic cardiovascular disease subtypes was compared across genetic similarity groups in 245\u2009388\n                      <jats:italic toggle=\"yes\">All of Us<\/jats:italic>\n                      participants. Groups genetically similar to European, African, admixed American, and remaining groups (combined as other) were used to assess PRS for CHD, IS, AAA, PAD, and multi-trait.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      PRS for CHD and AAA performed better than IS and PAD. For CHD, CHD\n                      <jats:sub>PGS003725<\/jats:sub>\n                      performed the best (hazard ratio per SD increase [95% CI]), across genetic ancestry groups, European, and African (1.72 [1.67\u20131.78], 1.23 [1.17\u20131.29]), with CHD\n                      <jats:sub>PGS004696<\/jats:sub>\n                      being best for admixed American (1.91 [1.70\u20132.15]), and CHD\n                      <jats:sub>PGS003356<\/jats:sub>\n                      for other (1.75 [1.58\u20131.95]). The best performing PRS for AAA was AAA\n                      <jats:sub>Multi<\/jats:sub>\n                      for European, other, and admixed American (1.71 [1.52\u20131.92], 1.59 [1.07\u20132.37], 1.50 [0.90\u20132.52]) and AAA\n                      <jats:sub>PGS003972<\/jats:sub>\n                      for African (1.39 [1.19\u20131.63]). For IS, IS\n                      <jats:sub>Multi<\/jats:sub>\n                      performed best for other and European (1.49 [1.17\u20131.89], 1.33 [1.25\u20131.42]), and IS\n                      <jats:sub>PGS000039<\/jats:sub>\n                      performed best in admixed American and African (1.17 [1.07\u20131.27], 1.09 [1.04\u20131.15]). For PAD, PAD\n                      <jats:sub>Multi<\/jats:sub>\n                      performed best for all groups (other, 1.51 [1.19\u20131.92]; European, 1.32 [1.24\u20131.41]; admixed American, 1.23 [1.05\u20131.45]; and African, 1.18 [1.04\u20131.34]).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>Multi-trait and multi-ancestry PRS performed better than individual trait and\/or single ancestry PRS for each atherosclerotic cardiovascular disease phenotype across ancestrally diverse and admixed individuals, with minimal change including adjustment for conventional risk factors.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circgen.125.005382","type":"journal-article","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T09:00:15Z","timestamp":1780909215000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Performance of Polygenic Risk Scores for Atherosclerotic Cardiovascular Disease in the\n                    <i>All of Us<\/i>\n                    Program"],"prefix":"10.1161","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5861-0413","authenticated-orcid":true,"given":"Johanna L.","family":"Smith","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine (J.L.S., K.N., M.E.H., O.D.), Mayo Clinic, Rochester, MN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristjan","family":"Norland","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine (J.L.S., K.N., M.E.H., O.D.), Mayo Clinic, Rochester, MN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1299-9969","authenticated-orcid":true,"given":"Marwan E.","family":"Hamed","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine (J.L.S., K.N., M.E.H., O.D.), Mayo Clinic, Rochester, MN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Quantitative Health Sciences (Y.Y., J.N., D.J.S.), Mayo Clinic, Rochester, MN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3435-1805","authenticated-orcid":true,"given":"Jie","family":"Na","sequence":"additional","affiliation":[{"name":"Department of Quantitative Health Sciences (Y.Y., J.N., D.J.S.), Mayo Clinic, Rochester, MN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9906-8608","authenticated-orcid":true,"given":"Ozan","family":"Dikilitas","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine (J.L.S., K.N., M.E.H., O.D.), Mayo Clinic, Rochester, MN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1457-6433","authenticated-orcid":true,"given":"Daniel J.","family":"Schaid","sequence":"additional","affiliation":[{"name":"Department of Quantitative Health Sciences (Y.Y., J.N., D.J.S.), Mayo Clinic, Rochester, MN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6524-3471","authenticated-orcid":true,"given":"Iftikhar J.","family":"Kullo","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Cardiovascular Research Center and the Mellowes Center for Genomic Sciences and Precision Medicine, Medical 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