{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Hou X"],"funding":["National Institute of Neurological Disorders and Stroke","Mangurian Foundation Lewy Body Dementia Program at Mayo Clinic","Ted Turner and Family","Mayo Clinic Office of Research Equity, Inclusion, and Diversity","The Little Family Foundation","Congressionally Directed Medical Research Programs","NIA NIH HHS","Mayo Clinic Robert and Arlene Kogod Center on Aging","Florida Department of Health-Ed, Ethel Moore Alzheimer's Disease Research Program","Alzheimer&apos;s Association","American Parkinson Disease Association Center for Advanced Research at Mayo Clinic Jacksonville","National Institute on Aging","American Brain Foundation","NINDS NIH HHS","The Michael J. Fox Foundation for Parkinson's Research","Alzheimer's Association","The Ted Nash Long Life Foundation","Mayo Clinic Center for Biomedical Discovery"],"pagination":["e70198"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12044520"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["21(4)"],"pubmed_abstract":["<h4>Introduction</h4>Phosphorylated ubiquitin (p-S65-Ub) is generated during PINK1-PRKN mitophagy as a specific marker of mitochondrial damage. Despite the widespread deposition of p-S65-Ub in aged and diseased human brain, the genetic contribution to its accumulation remains unclear.<h4>Methods</h4>To identify novel mitophagy regulators, we performed a genome-wide association study using p-S65-Ub level as a quantitative trait in 1012 autopsy-confirmed Lewy body disease (LBD) samples.<h4>Results</h4>We identified a significant genome-wide association with p-S65-Ub for rs429358 (apolipoprotein E ε4 [APOE4]) and a suggestive association for rs6480922 (ZMIZ1). APOE4 was associated with higher p-S65-Ub levels and greater neuropathological burden. Functional validation in mouse and human induce"],"journal":["Alzheimer's & dementia : the journal of the Alzheimer's Association"],"pubmed_title":["Genome-wide association analysis identifies APOE as a mitophagy modifier in Lewy body disease."],"pmcid":["PMC12044520"],"funding_grant_id":["R01 NS078086","U19 AG071754","U54 NS110435","R01 NS110085","P30 AG062677","R01 AG056366","U54NS110435","22A07","P30AG062677","R56 AG062556","U54 NS100693","U01NS100620","U54NS100693","22A05","RF1 AG046205","U01 NS100620","U19 AG069701","R01AG087165","R56AG062556","U19AG071754","RF1 NS085070","R01AG056366","P50 NS072187","R01 AG089380","AARF‐22‐973152","AARF-22-973152","R01AG089380","R01NS110085","U19AG069701","R01 AG087165","RF1NS085070","P50NS072187","RF1AG046205","W81XWH-17-1-0249","W81XWH‐17‐1‐0249","W81XWH‐17‐1‐0248","R01NS078086","W81XWH-17-1-0248"],"pubmed_authors":["Fiesel FC","Dickson DW","Heckman MG","Bu G","Ross OA","Guerreiro R","Hou X","Reddy JS","Zhao N","Valentino RR","Soto-Beasley AI","Springer W","Koga S","Bras J","White LJ","Johnson PW","Quicksall ZS","Zhao J","Watzlawik JO"],"additional_accession":[]},"is_claimable":false,"name":"Genome-wide association analysis identifies APOE as a mitophagy modifier in Lewy body disease.","description":"<h4>Introduction</h4>Phosphorylated ubiquitin (p-S65-Ub) is generated during PINK1-PRKN mitophagy as a specific marker of mitochondrial damage. Despite the widespread deposition of p-S65-Ub in aged and diseased human brain, the genetic contribution to its accumulation remains unclear.<h4>Methods</h4>To identify novel mitophagy regulators, we performed a genome-wide association study using p-S65-Ub level as a quantitative trait in 1012 autopsy-confirmed Lewy body disease (LBD) samples.<h4>Results</h4>We identified a significant genome-wide association with p-S65-Ub for rs429358 (apolipoprotein E ε4 [APOE4]) and a suggestive association for rs6480922 (ZMIZ1). APOE4 was associated with higher p-S65-Ub levels and greater neuropathological burden. Functional validation in mouse and human induce","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Apr","modification":"2026-06-02T06:40:27.079Z","creation":"2025-07-08T03:12:54.734Z"},"accession":"S-EPMC12044520","cross_references":{"pubmed":["40309932"],"doi":["10.1002/alz.70198"]}}