{"doi":"10.1002/alz.13113","title":"Validation of newly derived polygenic risk scores for dementia in a prospective study of older individuals","abstract":"INTRODUCTION: Recent genome-wide association studies identified new dementia-associated variants. We assessed the performance of updated polygenic risk scores (PRSs) using these variants in an independent cohort. METHODS: We used Cox models and area under the curve (AUC) to validate new PRSs (PRS-83SNP, PRS-SBayesR, and PRS-CS) compared with an older PRS-23SNP in 12,031 initially-healthy participants ≥70 years of age. Dementia was rigorously adjudicated according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria. RESULTS: PRS-83SNP, PRS-SBayesR, and PRS-CS were associated with incident dementia, with fully adjusted (including apolipoprotein E [APOE] ε4) hazard ratios per standard deviation (SD) of 1.35 (1.23-1.47), 1.37 (1.25-1.50), and 1.42 (1.30-1.56), respectively. The AUC of a model containing conventional/non-genetic factors and APOE was 74.7%. This was improved to 75.7% (p = 0.007), 76% (p = 0.004), and 76.1% (p = 0.003) with addition of PRS-83SNP, PRS-SBayesR, and PRS-CS, respectively. The PRS-23SNP did not improve AUC (74.7%, p = 0.95). CONCLUSION: New PRSs for dementia significantly improve risk-prediction performance, but still account for less risk than APOE genotype overall.","journal":"Alzheimer s & Dementia","year":2023,"id":328291,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":23,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.874,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":332013,"name":"Joanne Ryan","orcid":"0000-0002-7039-6325","position":1,"is_corresponding":false},{"id":351162,"name":"Suzanne G. Orchard","orcid":"0000-0003-0211-3183","position":2,"is_corresponding":false},{"id":1031171,"name":"Catherine Robb","orcid":"0000-0001-7586-5533","position":3,"is_corresponding":false},{"id":264292,"name":"Robyn L. Woods","orcid":"0000-0003-1249-6149","position":4,"is_corresponding":false},{"id":264293,"name":"Rory Wolfe","orcid":"0000-0002-2126-1045","position":5,"is_corresponding":false},{"id":65958,"name":"Alan E. Renton","orcid":"0000-0001-6702-8268","position":6,"is_corresponding":false},{"id":27629,"name":"Alison Goate","orcid":"0000-0002-0576-2472","position":7,"is_corresponding":false},{"id":285858,"name":"Amy Brodtmann","orcid":"0000-0001-9466-2862","position":8,"is_corresponding":false},{"id":284810,"name":"Raj C. Shah","orcid":"0000-0001-9706-9730","position":9,"is_corresponding":false},{"id":792045,"name":"Trevor T.‐J. Chong","orcid":"0000-0001-7764-3811","position":10,"is_corresponding":false},{"id":692607,"name":"Kerry M. Sheets","orcid":"0000-0002-3492-2404","position":11,"is_corresponding":false},{"id":1049688,"name":"Christopher Kyndt","orcid":"0009-0005-5871-2662","position":12,"is_corresponding":false},{"id":765530,"name":"A. K. Sood","orcid":"0000-0002-4157-361X","position":13,"is_corresponding":false},{"id":323248,"name":"Elsdon Storey","orcid":"0000-0001-5887-3267","position":14,"is_corresponding":false},{"id":104607,"name":"Anne M. Murray","orcid":"0000-0002-2787-8433","position":15,"is_corresponding":false},{"id":264297,"name":"John J. McNeil","orcid":"0000-0002-1049-5129","position":16,"is_corresponding":false},{"id":301792,"name":"Paul Lacaze","orcid":"0000-0002-0902-6798","position":17,"is_corresponding":false},{"id":436268,"name":"Chenglong Yu","orcid":"0000-0002-0546-2779","position":0,"is_corresponding":true}],"reference_count":59,"raw_metadata":null,"created_at":"2026-07-19T01:08:52.196069Z","pmid":"37177856","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}