{"doi":"10.1002/alz.70358","title":"Genome‐wide association analyses identify candidate loci for amyloid imaging and plasma biomarkers in adults with Down syndrome","abstract":"BACKGROUND: People with Down syndrome (DS) overproduce amyloid-beta (Aβ) due to triplication of the amyloid precursor protein (APP) gene on chromosome 21, and consequently accumulate brain amyloid load at younger ages. We conducted genome-wide association (GWA) analyses on amyloid imaging and plasma biomarkers to discern the genetic architecture of amyloid burden in DS. METHODS: GWA analyses were performed on amyloid positron emission tomography (PET) and plasma biomarkers (Aβ40, Aβ42, Aβ42/40 ratio) in participants from the Alzheimer's Biomarker Consortium-Down Syndrome (ABC-DS) and on plasma Aβ biomarkers available in an independent DS cohort, followed by meta-analysis of plasma Aβ biomarker data. RESULTS: Meta-analysis on plasma biomarkers identified four novel loci: two for Aβ42 (PFKFB3/rs147647642, p = 2.83E-08; DLX3-PICART1/rs12952028, p = 9.31E-09) and two for Aβ40 (LINC01941-GYPC/rs78338676, p = 9.33E-09; PDE4D/rs146261781, p = 9.97E-08). Five genome-wide signals were observed for amyloid-PET in the ABC-DS cohort that need confirmation in an independent DS dataset. DISCUSSION: Despite the small sample, our findings highlight the unique genetic architecture of amyloid burden in DS. HIGHLIGHTS: Genetic markers for amyloid biomarkers in Down syndrome (DS) were identified. Meta-analyses identified four novel loci for plasma amyloid in two DS cohorts. Five loci associated with amyloid positron emission tomography levels were identified in the Alzheimer's Biomarker Consortium-Down Syndrome cohort. Multi-trait analysis revealed loci linking variants to amyloid biomarkers.","journal":"Alzheimer s & Dementia","year":2025,"id":570460,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9099,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":819166,"name":"Lam‐Ha T. Dang","orcid":"0000-0002-3232-3088","position":1,"is_corresponding":false},{"id":1091694,"name":"Ruyu Shi","orcid":"0009-0004-3230-2625","position":2,"is_corresponding":false},{"id":901055,"name":"Kang-Hsien Fan","orcid":"0000-0003-0121-3959","position":3,"is_corresponding":false},{"id":1354076,"name":"Asma Naseer Cheema","orcid":"0000-0002-9239-7601","position":4,"is_corresponding":false},{"id":893996,"name":"Laura Xicota","orcid":"0000-0003-2832-9214","position":5,"is_corresponding":false},{"id":275735,"name":"Davneet Minhas","orcid":"0000-0002-0217-6777","position":6,"is_corresponding":false},{"id":1051527,"name":"Weiquan Luo","orcid":null,"position":7,"is_corresponding":false},{"id":1354077,"name":"Narges Zafari","orcid":"0000-0002-9115-3146","position":8,"is_corresponding":false},{"id":1092592,"name":"Vibha Acharya","orcid":"0009-0003-0910-659X","position":9,"is_corresponding":false},{"id":284228,"name":"Eleanor Feingold","orcid":"0000-0003-2898-6484","position":10,"is_corresponding":false},{"id":270468,"name":"Sharon J. Krinsky‐McHale","orcid":"0000-0002-7205-7319","position":11,"is_corresponding":false},{"id":275732,"name":"Charles M. Laymon","orcid":"0000-0002-5966-7219","position":12,"is_corresponding":false},{"id":329924,"name":"Ann D. Cohen","orcid":"0000-0001-7395-9624","position":13,"is_corresponding":false},{"id":270459,"name":"Benjamin L. Handen","orcid":"0000-0001-9550-1665","position":14,"is_corresponding":false},{"id":861881,"name":"Bradley Christian","orcid":"0000-0001-5072-3512","position":15,"is_corresponding":false},{"id":270466,"name":"Elizabeth Head","orcid":"0000-0003-1115-6396","position":16,"is_corresponding":false},{"id":80305,"name":"Mark Mapstone","orcid":"0000-0003-0280-8057","position":17,"is_corresponding":false},{"id":270463,"name":"Joseph H. Lee","orcid":"0000-0002-2000-4821","position":18,"is_corresponding":false},{"id":867455,"name":"Carlos Cruchaga","orcid":"0000-0002-5261-689X","position":19,"is_corresponding":false},{"id":544014,"name":"M. Ilyas Kamboh","orcid":"0000-0002-3453-1438","position":20,"is_corresponding":false},{"id":901056,"name":"Muhammad Aslam","orcid":"0000-0003-1817-7894","position":0,"is_corresponding":true}],"reference_count":65,"raw_metadata":null,"created_at":"2026-07-19T02:57:07.857542Z","pmid":"40667702","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":[]}