biostudies-literatureUnknownAkcimen FIntramural NIH HHSNIH HHSElucidating the genetic contributions to Parkinson's disease (PD) etiology across diverse ancestries is a critical priority for the development of targeted therapies in a global context. We conducted the largest sequencing characterization of potentially disease-causing, protein-altering and splicing mutations in 710 cases and 11,827 controls from genetically predicted African or African admixed ancestries. We explored copy number variants (CNVs) and runs of homozygosity (ROHs) in prioritized early onset and familial cases. Our study identified rare <i>GBA1</i> coding variants to be the most frequent mutations among PD patients, with a frequency of 4% in our case cohort. Out of the 18 <i>GBA1</i> variants identified, ten were previously classified as pathogenic or likely pathogenic, four wmedRxiv : the preprint server for health sciences2025.01.14.25320205https://www.ebi.ac.uk/biostudies/studies/S-EPMC11759243biostudies-literatureLarge-scale genetic characterization of Parkinson's disease in the African and African admixed populations.PMC11759243OT2 OD027852OT2 OD026548OT2 OD025337OT2 OD025315OT2 OD026549OT2 OD025277OT2 OD025276OT2 OD027060U24 OD023121OT2 OD032100U24 OD023163U2C OD023196OT2 OD026555OT2 OD026554OT2 OD026557OT2 OD026556OT2 OD023205OT2 OD023206ZIA AG000949OT2 OD026551OT2 OD026550OT2 OD026553OT2 OD026552ZIA NS003154U24 OD023176Nwani POnwuegbuzie GOjini FAbiodun OKoretsky MJAchoru COdeniyi OBello AStandaert DImarhiagbe FEspay ALouie NJerez PAIwaki HAamodt WAbubakar SAbdulai FDahodwala NStep KTraurig RNyandaiti YGlobal Parkinson’s Genetics Program (GP2)Levine KIbrahim ASukumar GDalgard CMakarious MBNwazor EBillingsley KMorris HRNalls MANorris SABlack and African American Connections to Parkinson’s Disease Study (BLAAC PD)Kilbane CAkinyemi RBardien SFang ZHFoster EROkubadejo NGalvelis KGVitale DCrea PWBreaux SOlusanya AOsemwegie NOshinaike OStaisch JOdiase FWahab KRacial Disparities in Parkinson Disease (RaD-PD)Chahine LMNwaokorie FOlanigan RTaiwo FSamuel SDaida KKomolafe MKlein CLeonard HLOkereke CAmeri AHernandez DGOjo OIdowu AArepalli SHill EStimming EFOwolabi LXie THoulden HOzomma SHernandez CFObianozie NAgabi OAkcimen FPaquette KIwuozo EAnyanwu RShamim EAFactor SOwolabi RAlaofin WGrant SHardy JIshola IBlauwendraat CHall DAErameh CNnama APadmanaban MKhani MLee PSReal RBranson COyakhire SChandra SDisbrow ESolle JOsaigbovo GIsayan MShulman LMSingleton ABBandres-Ciga SEzuduemoih DMalik LOgunmodede ARawls ANigeria Parkinson’s Disease Research Network (NPDRN)Ikwenu EOgbimi EMHinson VSa'ad FDean MSaffie-Awad PfalseLarge-scale genetic characterization of Parkinson's disease in the African and African admixed populations.Elucidating the genetic contributions to Parkinson's disease (PD) etiology across diverse ancestries is a critical priority for the development of targeted therapies in a global context. We conducted the largest sequencing characterization of potentially disease-causing, protein-altering and splicing mutations in 710 cases and 11,827 controls from genetically predicted African or African admixed ancestries. We explored copy number variants (CNVs) and runs of homozygosity (ROHs) in prioritized early onset and familial cases. Our study identified rare <i>GBA1</i> coding variants to be the most frequent mutations among PD patients, with a frequency of 4% in our case cohort. Out of the 18 <i>GBA1</i> variants identified, ten were previously classified as pathogenic or likely pathogenic, four w2025-01-01T00:00:00Z2025 Jan2026-04-08T19:49:18.112Z2025-04-19T21:18:23.043ZS-EPMC117592433986738010.1101/2025.01.14.25320205