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We assessed the performance of updated polygenic risk scores (PRSs) using these variants in an independent cohort.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We used Cox models and area under the curve (AUC) to validate new PRSs (PRS\u201083SNP, PRS\u2010SBayesR, and PRS\u2010CS) compared with an older PRS\u201023SNP in 12,031 initially\u2010healthy participants \u226570 years of age. Dementia was rigorously adjudicated according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM\u2010IV) criteria.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      PRS\u201083SNP, PRS\u2010SBayesR, and PRS\u2010CS were associated with incident dementia, with fully adjusted (including apolipoprotein E [\n                      <jats:italic>APOE<\/jats:italic>\n                      ] \u03b54) hazard ratios per standard deviation (SD) of 1.35 (1.23\u20131.47), 1.37 (1.25\u20131.50), and 1.42 (1.30\u20131.56), respectively. The AUC of a model containing conventional\/non\u2010genetic factors and\n                      <jats:italic>APOE<\/jats:italic>\n                      was 74.7%. This was improved to 75.7% (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.007), 76% (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.004), and 76.1% (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.003) with addition of PRS\u201083SNP, PRS\u2010SBayesR, and PRS\u2010CS, respectively. The PRS\u201023SNP did not improve AUC (74.7%,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.95).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>\n                      New PRSs for dementia significantly improve risk\u2010prediction performance, but still account for less risk than\n                      <jats:italic>APOE<\/jats:italic>\n                      genotype overall.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.13113","type":"journal-article","created":{"date-parts":[[2023,5,13]],"date-time":"2023-05-13T02:39:55Z","timestamp":1683945595000},"page":"5333-5342","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Validation of newly derived polygenic risk scores for dementia in a prospective study of older individuals"],"prefix":"10.1002","volume":"19","author":[{"given":"Chenglong","family":"Yu","sequence":"first","affiliation":[{"name":"School of Public Health and Preventive Medicine Monash University  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne","family":"Ryan","sequence":"additional","affiliation":[{"name":"School of Public Health and Preventive Medicine Monash University  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne G.","family":"Orchard","sequence":"additional","affiliation":[{"name":"School of Public Health and Preventive Medicine Monash University  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Robb","sequence":"additional","affiliation":[{"name":"School of Public Health and Preventive Medicine Monash University  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robyn L.","family":"Woods","sequence":"additional","affiliation":[{"name":"School of Public Health and Preventive Medicine Monash University  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rory","family":"Wolfe","sequence":"additional","affiliation":[{"name":"School of Public Health and Preventive Medicine Monash University  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan E.","family":"Renton","sequence":"additional","affiliation":[{"name":"Department Genetics and Genomic Sciences and Ronald M. 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