{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Bradley J"],"funding":["Office of Research and Development","Vahram Haroutunian","Emory University","National Institutes of Health","Alzheimer&apos;s Association","the Canadian Institute of Health Research","National Institute on Aging","Washington University","International Parkinson Fonds","Duke University","University of California, San Diego","North Bristol NHS Trust Research and Innovation Department and DeNDRoN","Meso Scale Diagnostics, LLC.","Araclon Biotech","US Department of Veterans Affairs Administration","Alzheimer's Association","Cure PSP","NIH HHS","Scott Noggle","Alzheimer's Disease Cooperative Study","North Carolina A&T University","Chan Zuckerberg Initiative","Boston University","Netherlands Brain Bank","Lara Mangravite","National Cell Repository for Alzheimer's Disease","Vanderbilt University","Wellcome Trust","University of Michigan","Philip De Jager","Internationale Stiching Alzheimer Onderzoek","University of Pennsylvania","IXICO Ltd.","University of California, San Francisco","Eisai Inc.","Laboratory for Neuro Imaging at the University of Southern California","Servei Anatomia Patologica","Transition Therapeutics","Glaxo Smith Kline","Alzheimer&apos;s Drug Discovery Foundation","University of California, Irvine","local NHS trusts and Newcastle University","South West Dementia Brain Bank","University of California, Los Angeles","National Institute of Biomedical Imaging and Bioengineering","Indiana University","NCRR NIH HHS","University of Arizona","Neurotrack Technologies","University of Southern California","AbbVie","Koichi Iijima","National Center for Geriatrics and Gerontology, Japan","London Brain Bank for Neurodegenerative Diseases","Mayo Clinic Brain Bank","Newcastle Brain Tissue Resource","Johnson & Johnson Pharmaceutical Research & Development LLC.","University of Washington","U.S. Department of Defense","Accelerating Medicines Partnership (AMP-AD)","NHGRI NIH HHS","Nilüfer Ertekin-Taner","Steven Younkin","Todd Golde","Lumosity","Johns Hopkins University","NIA NIH HHS","Oregon Health and Science University","Alzheimer's Drug Discovery Foundation","NIMH NIH HHS","University of Kentucky","Northwestern University","Rush University","Higher Education Funding Council for England (HEFCE), Alzheimer's Research Trust (ART)","Stichting MS Research","Sam Gandy","University of Wisconsin","University of Pittsburgh","EuroImmun","University of Alabama at Birmingham","Northern California Institute for Research and Education","NINDS NIH HHS","Sun Health Research Institute Brain and Body Donation Program","Servier","NeuroGenomics and Informatics Center","Michelle Ehrlich","National Institute on Aging Alzheimer's Disease Data Storage Site","Alzheimer's Association Zenith Fellows Award","Janssen Alzheimer Immunotherapy Research & Development, LLC.","Elan Pharmaceuticals, Inc.","Mount Sinai/JJ Peters VA Medical Center NIH Brain and Tissue Repository","Arizona Department of Health Services and the Arizona Biomedical Research Commission","Department of Defense","University of Miami","Nathan Price","Massachusetts General Hospital","Institut de Neuropatologia","Columbia University","Medical Research Council","Genotype-Tissue Expression (GTEx","New York University","Michael J. 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Byrd Sr. Alzheimer's Institute","NCI NIH HHS","Bin Zhang"],"pagination":["e70377"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12187977"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["21(6)"],"pubmed_abstract":["<h4>Introduction</h4>Most genetic studies for Alzheimer's disease (AD) have been focused on late-onset AD (LOAD). There are no large genetic studies on early-onset AD (EOAD).<h4>Methods</h4>We performed a multi-ancestry (non-Hispanic European, African, and East Asian) genome-wide association study (GWAS) including a total of 7,349 cases and 17,887 control. Cases with age at onset younger than 70 years were included. Sensitivity analysis including cases with onset <65 was performed. Only controls older than 70 were included to decrease the risk of developing LOAD.<h4>Results</h4>We identified eight novel significant loci: six in the ancestry-specific analyses and two in the trans-ancestry analysis. By integrating gene-based analysis, expression quantitative trait loci (eQTL), protein quanti"],"journal":["Alzheimer's & dementia : the journal of the Alzheimer's Association"],"pubmed_title":["Novel early-onset Alzheimer-associated genes influence risk through dysregulation of glutamate, immune activation, and intracellular signaling pathways."],"pmcid":["PMC12187977"],"funding_grant_id":["ZEN-22-848604","IIRG-05-14147","RF1AG058501","R01 AG01101","U24 AG026395","R01 AG009956","AG041232","UO1 HG004610","R01 AG019085","R37 AG015473","U24 AG026390","U24AG061340","P30 AG066444","P30 AG019610","R01 AG022018","R01 AG048927","U01 AG046170","U01 AG10483","R01 AG027944","KL2 RR024151","R00AG062723","R01 AG022374","R01 AG030146","P30 AG010124","P30 AG012300","U01AG046170","R01 AG17917","R01 AG017173","R01 AG018023","RF1 AG058501","R01 AG037212","RF1 AG053303","R01AG003949","R01 AG019757","R01 AG042437","P50 MH060451","RC2 AG036502","U01 AG032984","U24-AG041689","P50 NS039764","U24 AG041689","P01 AG003991","U01AG006786","R01AG041797","UO1 HG006375","AG027944","R01AG044546","P30 AG010133","R01 AG036836","P01 AG019724","P50 AG005681","R01 AG012101","P50AG033514","P50 AG008671","R01 AG032990","P30AG10161","U24 AG021886","U24 NS072026","P01 AG002219","R01 AG044546","U01 AG046152","R01 AG026916","RF1AG074007","R01NS080820","R01 AG041797","R01AG025711","R01AG036836","P30 AG008051","R01 MH080295","P30 AG010129","P50 AG016582","P50 AG025688","RF1AG053303","P01AG03991","R01 AG041718","U24 AG061340","R01AG032990","P50 AG016574","U01AG46152","R01 AG025259","P50 AG016573","R01 AG017917","R01AG17917","P50 AG016570","U01AG058922","UL1 RR029893","R01 AG013616","P30 AG10133","P30 AG08051","P50 AG005146","5R01AG012101","P50 AG025711","RF1 AG057440","P01 AG010491","AG021547","P50 AG005142","P30 AG066515","U01 AG046139","P50 AG005144","P01AG026276","U24NS072026","UO1 AG006781","R01AG019085","U01AG046139","AG041718","U01 AG058922","AG030653","R00 AG062723","R01AG042437","U24 AG21886","U54 AG052427","P50 AG008702","RF1AG057440","R01 AG15819","P30 AG010161","5R01AG022374","U01 HG006375","P01 AG003949","U24‐AG041689","U24 AG072122","R01 NS080820","IIRG-08-89720","AG05144","R01 AG28786-01A1","P50AG005136","U01 AG052410","R01 AG028786","AG07562","R01 AG015819","U01 AG061356","P30 AG013846","P30 AG028383","W81XWH‐12‐2‐0012","AG025688","P50 AG005128","P30AG19610","U01 AG010483","P30 AG008017","R01 AG030653","U01AG61356","P50AG005681","P50 AG033514","R01 AG026390","U01 AG006786","R01 AG031581","R01 CA129769","W81XWH-12-2-0012","U01 AG006781","5R01AG013616","R01 AG021547","P30 AG072975","P50AG016574","AG02365","1RC2AG036502","P50 AG023501","AG019757","RC2 AG036650","1R01AG035137","R01 AG22018","A2111048","P30 AG013854","R01 AG041232","P50 AG005138","P30AG72975","R01AG017216","U01AG006576","R01 AG009029","P50 AG005134","U01 HG004610","P30 AG028377","P50 AG005136","R01 NS059873","R01AG018023","RF1 AG074007","P50 AG005131","R01AG33193","P01 AG017216","P50 AG005133","R01 AG035137","R01 AG020688","RC2 AG036528","R01 AG033193","AG05128","P01AG003991","P20 MD000546","P30AG066444","P01 AG026276","U01 HG008657","U01 AG024904","AG010491","AG052410","R01AG15819"],"pubmed_authors":["Wang C","Martin ER","Reitz C","Naj AC","Schellenberg GD","Budde J","Cuccaro M","Pericak-Vance MA","Neupane A","Fernandez V","Kurup JT","Perrin RJ","Ray NR","Timsina J","Alzheimer's Disease Genetics Consortium (ADGC), Charles F. and Joanne Knight Alzheimer Disease Research Center (Knight‐ADRC)","Jean-Francois M","da Fonseca EL","Holtzman DM","Western D","Ali M","Haines J","Morris JC","Kunkle BW","Cruchaga C","Beecham GW","Bergmann K","Bradley J","Pottier C"],"additional_accession":[]},"is_claimable":false,"name":"Novel early-onset Alzheimer-associated genes influence risk through dysregulation of glutamate, immune activation, and intracellular signaling pathways.","description":"<h4>Introduction</h4>Most genetic studies for Alzheimer's disease (AD) have been focused on late-onset AD (LOAD). There are no large genetic studies on early-onset AD (EOAD).<h4>Methods</h4>We performed a multi-ancestry (non-Hispanic European, African, and East Asian) genome-wide association study (GWAS) including a total of 7,349 cases and 17,887 control. Cases with age at onset younger than 70 years were included. Sensitivity analysis including cases with onset <65 was performed. Only controls older than 70 were included to decrease the risk of developing LOAD.<h4>Results</h4>We identified eight novel significant loci: six in the ancestry-specific analyses and two in the trans-ancestry analysis. By integrating gene-based analysis, expression quantitative trait loci (eQTL), protein quanti","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Jun","modification":"2026-06-03T07:27:35.894Z","creation":"2026-04-25T03:22:33.972Z"},"accession":"S-EPMC12187977","cross_references":{"pubmed":["40556318"],"doi":["10.1002/alz.70377"]}}