{"doi":"10.1002/alz.14045","title":"Genetic analysis of cognitive preservation in the midwestern Amish reveals a novel locus on chromosome 2","abstract":"INTRODUCTION: Alzheimer's disease (AD) remains a debilitating condition with limited treatments and additional therapeutic targets needed. Identifying AD protective genetic loci may identify new targets and accelerate identification of therapeutic treatments. We examined a founder population to identify loci associated with cognitive preservation into advanced age. METHODS: Genome-wide association and linkage analyses were performed on 946 examined and sampled Amish individuals, aged 76-95, who were either cognitively unimpaired (CU) or impaired (CI). RESULTS: ) with cognitive preservation. Genetic linkage analyses identified > 100 significant (logarithm of the odds [LOD] ≥ 3.3) SNPs, some which overlapped with the association results. Only one locus on chromosome 2 retained significance across multiple analyses. DISCUSSION: A novel significant result for cognitive preservation on chromosome 2 includes the genes LRRTM4 and CTNNA2. Additionally, the lead SNP, rs1402906, impacts the POU3F2 transcription factor binding affinity, which regulates LRRTM4 and CTNNA2. HIGHLIGHTS: GWAS and linkage identified over 100 loci associated with cognitive preservation. One locus on Chromosome 2 retained significance over multiple analyses. Predicted TFBSs near rs1402906 regulate genes associated with neurocognition.","journal":"Alzheimer s & Dementia","year":2024,"id":463376,"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":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9056,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":437428,"name":"Yeunjoo E. Song","orcid":"0000-0002-7452-3731","position":1,"is_corresponding":false},{"id":821832,"name":"Audrey Lynn","orcid":null,"position":2,"is_corresponding":false},{"id":801662,"name":"Reneé A. Laux","orcid":null,"position":3,"is_corresponding":false},{"id":821187,"name":"Kristy Miskimen","orcid":"0000-0003-0376-9053","position":4,"is_corresponding":false},{"id":747285,"name":"Michael D. Osterman","orcid":"0000-0003-4302-6596","position":5,"is_corresponding":false},{"id":40214,"name":"Michael L. Cuccaro","orcid":"0000-0003-4769-0785","position":6,"is_corresponding":false},{"id":67007,"name":"Paula Ogrocki","orcid":null,"position":7,"is_corresponding":false},{"id":233800,"name":"Alan J. Lerner","orcid":"0000-0001-9447-6154","position":8,"is_corresponding":false},{"id":40758,"name":"Jeffery M. Vance","orcid":"0000-0003-3815-8199","position":9,"is_corresponding":false},{"id":801664,"name":"Denise Fuzzell","orcid":null,"position":10,"is_corresponding":false},{"id":801665,"name":"Sarada L. Fuzzell","orcid":null,"position":11,"is_corresponding":false},{"id":821834,"name":"Sherri D. Hochstetler","orcid":null,"position":12,"is_corresponding":false},{"id":405943,"name":"Daniel A. Dorfsman","orcid":null,"position":13,"is_corresponding":false},{"id":821829,"name":"Laura J. Caywood","orcid":null,"position":14,"is_corresponding":false},{"id":580853,"name":"Michael B. Prough","orcid":null,"position":15,"is_corresponding":false},{"id":405945,"name":"Larry D. Adams","orcid":null,"position":16,"is_corresponding":false},{"id":821830,"name":"Jason E. Clouse","orcid":null,"position":17,"is_corresponding":false},{"id":821831,"name":"Sharlene D. Herington","orcid":null,"position":18,"is_corresponding":false},{"id":437430,"name":"William K. Scott","orcid":"0000-0001-9336-6404","position":19,"is_corresponding":false},{"id":6903,"name":"Margaret A. Pericak‐Vance","orcid":"0000-0001-7283-8804","position":20,"is_corresponding":false},{"id":6896,"name":"Jonathan L. Haines","orcid":"0000-0002-4351-4728","position":21,"is_corresponding":false},{"id":821188,"name":"Leighanne R. Main","orcid":"0000-0002-8828-8066","position":0,"is_corresponding":true}],"reference_count":77,"raw_metadata":null,"created_at":"2026-07-19T02:04:28.838123Z","pmid":"39376159","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":[]}