{"doi":"10.1002/alz.13064","title":"Meta‐analysis of age‐related cognitive decline reveals a novel locus for the attention domain and implicates a COVID‐19‐related gene for global cognitive function","abstract":"INTRODUCTION: Cognitive abilities have substantial heritability throughout life, as shown by twin- and population-based studies. However, there is limited understanding of the genetic factors related to cognitive decline in aging across neurocognitive domains. METHODS: We conducted a meta-analysis on 3045 individuals aged ≥65, derived from three population-based cohorts, to identify genetic variants associated with the decline of five neurocognitive domains (attention, memory, executive function, language, visuospatial function) and global cognitive decline. We also conducted gene-based and functional bioinformatics analyses. RESULTS: Apolipoprotein E (APOE)4 was significantly associated with decline of memory (p = 5.58E-09) and global cognitive function (p = 1.84E-08). We identified a novel association with attention decline on chromosome 9, rs6559700 (p = 2.69E-08), near RASEF. Gene-based analysis also identified a novel gene, TMPRSS11D, involved in the activation of SARS-CoV-2, to be associated with the decline in global cognitive function (p = 4.28E-07). DISCUSSION: Domain-specific genetic studies can aid in the identification of novel genes and pathways associated with decline across neurocognitive domains. HIGHLIGHTS: rs6559700 was associated with decline of attention. APOE4 was associated with decline of memory and global cognitive decline. TMPRSS11D, a gene involved in the activation of SARS-CoV-2, was implicated in global cognitive decline. Cognitive domain abilities had both unique and shared molecular pathways across the domains.","journal":"Alzheimer s & Dementia","year":2023,"id":349397,"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":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8614,"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":1085181,"name":"Kang‐Hsien Fan","orcid":null,"position":1,"is_corresponding":false},{"id":251492,"name":"Beth E. Snitz","orcid":"0000-0002-9978-1374","position":2,"is_corresponding":false},{"id":251490,"name":"Mary Ganguli","orcid":"0000-0003-2762-7105","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":1092592,"name":"Vibha Acharya","orcid":"0009-0003-0910-659X","position":0,"is_corresponding":true}],"reference_count":60,"raw_metadata":null,"created_at":"2026-07-19T01:12:14.919810Z","pmid":"37089073","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":[]}