{"doi":"10.3233/jad-220293","title":"Genome-Wide Association Study of Incident Dementia in a Community-Based Sample of Older Subjects","abstract":"BACKGROUND: Alzheimer's disease (AD) is a complex disease influenced by the environment and genetics; however, much of the genetic component remains unaccounted for. OBJECTIVE: The purpose of this work was to use genome-wide association analyses to detect genetic associations with incident AD in a sample of older adults aged 75 and above. METHODS: We performed a genome-wide association study (GWAS) on genome-wide genotyped and imputed data (14,072,053 variants) on the Gingko Evaluation of Memory (GEM) study sample consisting of 424 incident dementia (mean age = 84.46±3.91) and 2,206 non-demented (mean age = 84.55±3.23) subjects. RESULTS: The established association of APOE*4 carriers with AD was confirmed in this community-based sample of older subjects (odds ratio (OR) = 2.22; p = 9.36E-14) and was stronger in females (OR = 2.72; p = 1.74E-10) than in males (OR = 1.88; p = 2.43E-05). We observed a novel genome-wide significant (GWS) locus on chromosome 12 near ncRNA LOC105369711/rs148377161 (OR = 3.31; p = 1.66E-08). In addition, sex-stratified analyses identified two novel associations in males: one near ncRNA LOC729987/rs140076909 on chromosome 1 (OR = 4.51; p = 3.72E-08) and the other approaching GWS near ncRNA LOC105375138/rs117803234 on chromosome 7 (OR = 3.76; p = 6.93E-08). CONCLUSION: The use of community-based samples of older individuals and incident dementia as a phenotype may be a helpful approach for the identification of novel genes for AD, which may not be detected in standard case-control studies. Replication of these signals and further studies of these regions and genes will help to provide a clearer picture for their role in AD.","journal":"Journal of Alzheimer s Disease","year":2022,"id":254390,"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":21,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.6629,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":901055,"name":"Kang-Hsien Fan","orcid":"0000-0003-0121-3959","position":1,"is_corresponding":false},{"id":901056,"name":"Muhammad Aslam","orcid":"0000-0003-1817-7894","position":2,"is_corresponding":false},{"id":251492,"name":"Beth E. Snitz","orcid":"0000-0002-9978-1374","position":3,"is_corresponding":false},{"id":70543,"name":"Steven T. DeKosky","orcid":"0000-0003-3743-2758","position":4,"is_corresponding":false},{"id":245369,"name":"Oscar L. López","orcid":"0000-0002-8546-8256","position":5,"is_corresponding":false},{"id":284228,"name":"Eleanor Feingold","orcid":"0000-0003-2898-6484","position":6,"is_corresponding":false},{"id":544014,"name":"M. Ilyas Kamboh","orcid":"0000-0002-3453-1438","position":7,"is_corresponding":false},{"id":901481,"name":"Jordan D. Harper","orcid":null,"position":0,"is_corresponding":true}],"reference_count":22,"raw_metadata":null,"created_at":"2026-07-19T00:25:03.918844Z","pmid":"35694926","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":[]}