{"doi":"10.1002/ana.26131","title":"Polygenic Risk Score for Alzheimer's Disease in Caribbean Hispanics","abstract":"OBJECTIVE: Polygenic risk scores (PRSs) assess the individual genetic propensity to a condition by combining sparse information scattered across genetic loci, often displaying small effect sizes. Most PRSs are constructed in European-ancestry populations, limiting their use in other ethnicities. Here we constructed and validated a PRS for late-onset Alzheimer's Disease (LOAD) in Caribbean Hispanics (CH). METHODS: We used a CH discovery (n = 4,312) and independent validation sample (n = 1,850) to construct an ancestry-specific PRS (\"CH-PRS\") and evaluated its performance alone and with other predictors using the area under curve (AUC) and logistic regression (strength of association with LOAD and statistical significance). We tested if CH-PRS predicted conversion to LOAD in a subsample with longitudinal data (n = 1,239). We also tested the CH-PRS in an independent replication CH cohort (n = 200) and brain autopsy cohort (n = 33). Finally, we tested the effect of ancestry on PRS by using European and African American discovery cohorts to construct alternative PRSs (\"EUR-PRS\", \"AA-PRS\"). RESULTS: = 1.51 95%CI = 1.36-1.68), raising to >75% in APOE-ɛ4 non-carriers. CH-PRS alone achieved an AUC = 72% in the autopsy cohort, raising to AUC = 83% in full model. Higher CH-PRS was significantly associated with clinical LOAD in the replication CH cohort (OR = 1.61, 95%CI = 1.19-2.17) and significantly predicted conversion to LOAD (HR = 1.93, CI = 1.70-2.20) in the longitudinal subsample. EUR-PRS and AA-PRS reached lower prediction accuracy (AUC = 58% and 53%, respectively). INTERPRETATION: Enriching diversity in genetic studies is critical to provide an effective PRS in profiling LOAD risk across populations. ANN NEUROL 2021;90:366-376.","journal":"Annals of Neurology","year":2021,"id":165346,"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":36,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.585,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":355527,"name":"Daniel Felsky","orcid":"0000-0003-1831-9848","position":1,"is_corresponding":false},{"id":413237,"name":"Dolly Reyes‐Dumeyer","orcid":"0000-0003-3572-8248","position":2,"is_corresponding":false},{"id":688412,"name":"Ricky Lali","orcid":"0000-0002-9689-9414","position":3,"is_corresponding":false},{"id":413238,"name":"Rafael Lantigua","orcid":"0000-0003-4854-7331","position":4,"is_corresponding":false},{"id":63303,"name":"Badri N. Vardarajan","orcid":"0000-0002-5560-4085","position":5,"is_corresponding":false},{"id":618060,"name":"Ivonne Z. Jiménez‐Velázquez","orcid":"0000-0002-9943-1657","position":6,"is_corresponding":false},{"id":6896,"name":"Jonathan L. Haines","orcid":"0000-0002-4351-4728","position":7,"is_corresponding":false},{"id":605091,"name":"Gerard D. Shellenberg","orcid":null,"position":8,"is_corresponding":false},{"id":580857,"name":"Margaret A Pericak‐Vance","orcid":null,"position":9,"is_corresponding":false},{"id":240620,"name":"Guillaume Paré","orcid":"0000-0002-6795-4760","position":10,"is_corresponding":false},{"id":27608,"name":"Richard Mayeux","orcid":"0000-0001-6519-9696","position":11,"is_corresponding":false},{"id":560402,"name":"Giuseppe Tosto","orcid":"0000-0001-7075-8245","position":12,"is_corresponding":false},{"id":560401,"name":"Sanjeev Sariya","orcid":"0000-0002-3104-2348","position":0,"is_corresponding":true}],"reference_count":54,"raw_metadata":null,"created_at":"2026-07-18T23:45:36.425208Z","pmid":"34038570","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":[]}