{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Xicota L"],"funding":["National Institute on Aging (NIA)","National Center","NCATS NIH HHS","de Influencia Genetica en Alzheimer","NIA NIH HHS","Alzheimer's Association Zenith Fellows Award","National Institute on Aging Alzheimer's Disease Family Based Study","Phenotype Harmonization Consortium","BrightFocus Foundation","Early-Onset Alzheimer's Disease Whole-Genome Sequencing Project","Washington Heights-Inwood Columbia Aging Project","Bright Focus","Alzheimer's Disease Neuroimaging Initiative","Wisconsin Registry for Alzheimer's Prevention (WRAP)","Alzheimer's Association","NIH HHS"],"pagination":["e71188"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12928012"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["22(2)"],"pubmed_abstract":["<h4>Introduction</h4>Genetic contributors to early onset Alzheimer's disease (AD) beyond APP and PSEN1/2 remain unknown. Identifying novel loci may reveal disease mechanisms and therapeutic targets. We investigated genetic variants influencing age at onset in early onset families from the Long-Life Family Study (LLFS).<h4>Methods</h4>Six families with at least two early onset cases (onset ≤ 65) were identified among 3476 LLFS participants. Genome-wide linkage analysis of age at onset was followed by single nucleotide polymorphism association. Validation analyses were performed in nine independent cohorts, alongside blood and brain transcriptomic analyses.<h4>Results</h4>Three significant linkage regions were identified, including RBFOX1 (logarithm of the odds = 4.41). RBFOX1 variants were associated with age at onset and cognitive phenotypes. A consistent association of RBFOX1 was observed across validation cohorts. Blood transcriptomics revealed RBFOX1 overexpression was associated with an earlier onset.<h4>Discussion</h4>RBFOX1 may influence AD age of onset, nominating the gene as a potential therapeutic target for delaying or preventing dementia."],"journal":["Alzheimer's & dementia : the journal of the Alzheimer's Association"],"pubmed_title":["RBFOX1 association with age at onset of Alzheimer's disease."],"pmcid":["PMC12928012"],"funding_grant_id":["ZEN-22-848604","AG072474","R01AG041797","R56 AG051876","U19 AG063893","A2015633S","UL1TR001873","U01AG068057","U24AG026395","AG066107","R01AG058918","U01-AG023749","U24AG074855","R01AG059716","U01-AG023744","U01-AG023755","R01AG067501","U01-AG023712"],"pubmed_authors":["Xicota L","Zmuda JM","Mayeux R","Wojczynski M","Long‐Life Family Study (LLFS), Estudio Familiar de Influencia Genetica en Alzheimer (EFIGA), and The National Institute on Aging Alzheimer's Disease Family Based Study (NIA‐LOAD FBS)","Vardarajan BV","Feitosa MF","Reyes-Dumeyer D","Hohman TJ","Contreras AG","Cruchaga C","Andersen SL","Cheng R","Bradley J","Cosentino S","Barral S","Lee JH"],"additional_accession":[]},"is_claimable":false,"name":"RBFOX1 association with age at onset of Alzheimer's disease.","description":"<h4>Introduction</h4>Genetic contributors to early onset Alzheimer's disease (AD) beyond APP and PSEN1/2 remain unknown. Identifying novel loci may reveal disease mechanisms and therapeutic targets. We investigated genetic variants influencing age at onset in early onset families from the Long-Life Family Study (LLFS).<h4>Methods</h4>Six families with at least two early onset cases (onset ≤ 65) were identified among 3476 LLFS participants. Genome-wide linkage analysis of age at onset was followed by single nucleotide polymorphism association. Validation analyses were performed in nine independent cohorts, alongside blood and brain transcriptomic analyses.<h4>Results</h4>Three significant linkage regions were identified, including RBFOX1 (logarithm of the odds = 4.41). RBFOX1 variants were associated with age at onset and cognitive phenotypes. A consistent association of RBFOX1 was observed across validation cohorts. Blood transcriptomics revealed RBFOX1 overexpression was associated with an earlier onset.<h4>Discussion</h4>RBFOX1 may influence AD age of onset, nominating the gene as a potential therapeutic target for delaying or preventing dementia.","dates":{"release":"2026-01-01T00:00:00Z","publication":"2026 Feb","modification":"2026-07-09T12:15:57.215Z","creation":"2026-07-09T11:15:07.536Z"},"accession":"S-EPMC12928012","cross_references":{"pubmed":["41724706"],"doi":["10.1002/alz.71188"]}}