{"doi":"10.1101/2021.01.08.21249413","title":"Polygenic Risk Scores for Alzheimer’s Disease and Mild Cognitive Impairment in Hispanics/Latinos in the U.S: The Study of Latinos – Investigation of Neurocognitive Aging","abstract":"Abstract Introduction Polygenic Risk Score (PRS) are powerful summaries of genetic risk alleles that can potentially be used to predict disease outcomes and guide treatment decisions. Hispanics/Latinos suffer from higher rates of Alzheimer’s Disease (AD) and Mild Cognitive Impairment (MCI) compared to non-Hispanic Whites, yet the strongest known genetic risk factor for AD, APOE - ϵ 4 allele, has weak association with AD in Hispanics/Latinos. We evaluated PRS constructed based on Genome-Wide Association Studies (GWAS) of AD in predicting MCI in Hispanics/Latinos when accounting for APOE alleles and variants. Methods We used summary statistics from four GWAS of AD to construct PRS that predict MCI in 4,189 diverse Hispanics/Latinos (mean age 63 years, 47% males) from the Study of Latinos-Investigation of Neurocognitive Aging. We assessed the PRS associations with MCI in the combined set of people and in groups defined by genetic ancestry and Hispanic/Latino background, and when including and excluding single nucleotide polymorphisms (SNPs) from the APOE gene region. Results A PRS constructed based on GWAS of AD in the FINNGEN Biobank was associated with MCI (OR = 1.34, 95% CI [1.15, 1.55]), and its association was mostly driven by 158 APOE region SNPs. A PRS constructed based on a multi-ethnic AD GWAS was associated with MCI (OR=1.22, 95% CI [1.08, 1.37]) without including any APOE region SNPs. APOE - ϵ 4 and APOE - ϵ 2 alleles were not associated with MCI. Discussion A combination of APOE region SNPs is associated with MCI in Hispanics/Latinos despite APOE - ϵ 4 and APOE - ϵ 2 alleles not being associated with MCI.","journal":"medRxiv","year":2021,"id":215720,"datarank":0.26876392038420827,"base_score":1.791759469228055,"endowment":1.791759469228055,"self_citation_contribution":0.26876392038420827,"citation_network_contribution":0.0,"self_endowment_contribution":0.26876392038420827,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9501,"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":306091,"name":"Nuzulul Kurniansyah","orcid":null,"position":1,"is_corresponding":false},{"id":303805,"name":"Einat Granot‐Hershkovitz","orcid":"0000-0003-0645-2713","position":2,"is_corresponding":false},{"id":651499,"name":"Matthew Goodman","orcid":"0000-0002-3982-7940","position":3,"is_corresponding":false},{"id":303806,"name":"Wassim Tarraf","orcid":"0000-0001-8888-7918","position":4,"is_corresponding":false},{"id":279133,"name":"Iris Broce","orcid":"0000-0003-4932-1430","position":5,"is_corresponding":false},{"id":234917,"name":"Richard B. Lipton","orcid":"0000-0003-2652-2897","position":6,"is_corresponding":false},{"id":37779,"name":"Martha L. Daviglus","orcid":"0000-0002-6791-8727","position":7,"is_corresponding":false},{"id":282469,"name":"Melissa Lamar","orcid":"0000-0001-6130-5543","position":8,"is_corresponding":false},{"id":303808,"name":"Sylvia Wassertheil‐Smoller","orcid":"0000-0002-5447-4653","position":9,"is_corresponding":false},{"id":336207,"name":"Jianwen Cai","orcid":"0000-0002-4945-6733","position":10,"is_corresponding":false},{"id":277082,"name":"Charles DeCarli","orcid":"0000-0003-1914-2693","position":11,"is_corresponding":false},{"id":303812,"name":"Hector M. González","orcid":"0000-0003-4867-7902","position":12,"is_corresponding":false},{"id":17640,"name":"Myriam Fornage","orcid":"0000-0003-0677-8158","position":13,"is_corresponding":false},{"id":17004,"name":"Tamar Sofer","orcid":"0000-0001-8520-8860","position":0,"is_corresponding":true}],"reference_count":47,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:53:00.192353Z","pmid":null,"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":[]}