{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Diaz-Ortiz ME"],"funding":["NIA NIH HHS","NINDS NIH HHS"],"pagination":["eabk0637"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9870036"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["377(6608)"],"pubmed_abstract":["Many risk loci for Parkinson's disease (PD) have been identified by genome-wide association studies (GWASs), but target genes and mechanisms remain largely unknown. We linked the GWAS-derived chromosome 7 locus (sentinel single-nucleotide polymorphism rs199347) to <i>GPNMB</i> through colocalization analyses of expression quantitative trait locus and PD risk signals, confirmed by allele-specific expression studies in the human brain. In cells, glycoprotein nonmetastatic melanoma protein B (GPNMB) coimmunoprecipitated and colocalized with α-synuclein (aSyn). In induced pluripotent stem cell-derived neurons, loss of <i>GPNMB</i> resulted in loss of ability to internalize aSyn fibrils and develop aSyn pathology. In 731 PD and 59 control biosamples, GPNMB was elevated in PD plasma, associating"],"journal":["Science (New York, N.Y.)"],"pubmed_title":["GPNMB confers risk for Parkinson's disease through interaction with α-synuclein."],"pmcid":["PMC9870036"],"funding_grant_id":["R01 NS082265","U19 AG062418","F31 NS113481","K23 NS114167","R01 NS115139","P50 NS053488","P30 AG072979"],"pubmed_authors":["Skrinak RT","Brody EM","Jain N","Charan R","Luk KC","Unger TL","Van Deerlin VM","Han N","Diaz-Ortiz ME","Clark E","Weintraub D","Posavi M","Gallagher MD","Davila-Rivera R","Seo Y","Carceles Cordon M","Zack R","Chen-Plotkin AS","Amari N","Lee EB","Tropea TF"],"additional_accession":[]},"is_claimable":false,"name":"GPNMB confers risk for Parkinson's disease through interaction with α-synuclein.","description":"Many risk loci for Parkinson's disease (PD) have been identified by genome-wide association studies (GWASs), but target genes and mechanisms remain largely unknown. We linked the GWAS-derived chromosome 7 locus (sentinel single-nucleotide polymorphism rs199347) to <i>GPNMB</i> through colocalization analyses of expression quantitative trait locus and PD risk signals, confirmed by allele-specific expression studies in the human brain. In cells, glycoprotein nonmetastatic melanoma protein B (GPNMB) coimmunoprecipitated and colocalized with α-synuclein (aSyn). In induced pluripotent stem cell-derived neurons, loss of <i>GPNMB</i> resulted in loss of ability to internalize aSyn fibrils and develop aSyn pathology. In 731 PD and 59 control biosamples, GPNMB was elevated in PD plasma, associating","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Aug","modification":"2025-04-22T10:14:58.757Z","creation":"2025-04-05T23:30:13.628Z"},"accession":"S-EPMC9870036","cross_references":{"pubmed":["35981040"],"doi":["10.1126/science.abk0637"]}}