ArticlemedRxiv : the preprint server for health sciences2025
Large-scale genetic characterization of Parkinson's disease in the African and African admixed populations.
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114 authors.
Fulya AkçimenLaboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0003-0931-5247
Kimberly PaquetteCenter for Alzheimer's and Related Dementias, National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0003-3989-4614
Peter Wild CreaLaboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0001-8944-5716
Paula Saffie-AwadPrograma de Pós-Graduação em Ciências Médicas, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.ORCID 0000-0002-8056-365X
Charles AchoruJos University Teaching Hospital, Jos, Plateau State, Nigeria.ORCID 0000-0003-2904-2557
Funmilola TaiwoUniversity College Hospital, Ibadan, Oyo State, Nigeria.
Simon OzommaUniversity of Calabar Teaching Hospital, Calabar, Cross River State, Nigeria.
Gerald OnwuegbuzieUniversity of Abuja, Abuja, Federal Capital Territory, Nigeria.ORCID 0000-0002-5203-1074
Marzieh KhaniCenter for Alzheimer's and Related Dementias, National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Spencer GrantLaboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
Lukman OwolabiBayero University, Kano, Kano State, Nigeria.ORCID 0000-0001-9509-1440
Chiamaka OkerekeUniversity of Nigeria Teaching Hospital, Ituku-Ozalla, Enugu State, Nigeria.ORCID 0000-0002-0280-0410
Olajumoke OshinaikeLagos State University College Of Medicine, Ikeja, Lagos State, Nigeria.ORCID 0000-0002-6290-6866
Emmanuel IwuozoBenue State University, Makurdi, Benue State, Nigeria.ORCID 0000-0003-2378-3872
Paul Suhwan LeeLaboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
Shyngle OyakhireNational Hospital Abuja, Federal Capital Territory, Nigeria.ORCID 0000-0002-8442-9896
Nosakhare OsemwegieUniversity of Port Harcourt Teaching Hospital, Rivers State, Nigeria.ORCID 0000-0002-8725-2256
Kensuke DaidaLaboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0002-9177-9587
Sani AbubakarAhmadu Bello University, Zaria, Kaduna State, Nigeria.
Adedunni OlusanyaCollege of Medicine, University of Lagos, Idi-araba, Lagos State, Nigeria.ORCID 0000-0002-4806-0534
Mariam IsayanDepartment of Neurology and Neurosurgery, National Institute of Health, Yerevan, Armenia.ORCID 0009-0002-2387-5347
Rami TraurigCenter for Alzheimer's and Related Dementias, National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Adebimpe OgunmodedeFederal Medical Center, Owo, Ondo State, Nigeria.
Sarah SamuelUniversity of Maiduguri Teaching Hospital, Maiduguri, Borno State.ORCID 0000-0001-6178-8282
Mary B MakariousCenter for Alzheimer's and Related Dementias, National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0002-7978-1051
Fadimatu Sa'adFederal Teaching Hospital, Gombe, Gombe State, Nigeria.
Rashidat OlaniganLagos State University Teaching Hospital, Ikeja, Lagos State, Nigeria.ORCID 0009-0007-4762-8611
Kristin LevineCenter for Alzheimer's and Related Dementias, National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Ewere Marie OgbimiDelta State University, Abraka, Delta State, Nigeria.ORCID 0009-0005-3416-4999
Dan VitaleCenter for Alzheimer's and Related Dementias, National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Francis OdiaseUniversity of Benin, Benin City, Edo State, Nigeria.ORCID 0000-0001-9788-6482
Mathew J KoretskyCenter for Alzheimer's and Related Dementias, National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0003-4341-3991
Francis OjiniCollege of Medicine, University of Lagos, Idi-araba, Lagos State, Nigeria.ORCID 0000-0003-4108-4995
Olanike OdeniyiGeneral Hospital, Lagos Island, Lagos State, Nigeria.ORCID 0000-0002-8778-2230
Zih-Hua FangGerman Center for Neurodegenerative Diseases, DZNE, Tübingen, Germany.ORCID 0000-0002-0225-8772
Nkechi ObianozieUniversity of Abuja Teaching Hospital, Gwagwalada, Federal Capital Territory, Nigeria.ORCID 0000-0003-4327-3116
Deborah A HallDepartment of Neurological Sciences, Rush University Medical Center, Chicago, USA.
Ernest NwazorRivers State University Teaching Hospital, Port Harcourt, Rivers State, Nigeria.ORCID 0000-0001-7950-2449
Tao XieUniversity of Chicago Medicine, Department of Neurology, Chicago, USA.
Francisca NwaokorieCollege of Medicine, University of Lagos, Idi-araba, Lagos State, Nigeria.
Mahesh PadmanabanUniversity of Chicago Medicine, Department of Neurology, Chicago, USA.ORCID 0000-0002-7499-3661
Paul NwaniNnamdi Azikiwe University Teaching Hospital, Nnewi, Anambra State, Nigeria.ORCID 0000-0002-1665-2738
Ejaz A ShamimNational Institute of Neurological Disorders and Stroke, Bethesda, MD, USA.ORCID 0000-0003-0992-056X
Alero NnamaUniversity of Port Harcourt Teaching Hospital, Rivers State, Nigeria.ORCID 0009-0005-3164-6634
David StandaertUniversity of Alabama at Birmingham, Department of Neurology, Birmingham, USA.ORCID 0000-0003-2921-8348
Morenikeji KomolafeObafemi Awolowo University, Ile-Ife, Osun State, Nigeria.ORCID 0000-0002-0592-5120
Marissa DeanUniversity of Alabama at Birmingham, Department of Neurology, Birmingham, USA.
Godwin OsaigbovoJos University Teaching Hospital, Jos, Plateau State, Nigeria.
Elizabeth DisbrowDepartment of Neurology, LSU Health Shreveport, LSU Health Shreveport Center for Brain Health, Shreveport, USA.ORCID 0000-0002-2133-3221
Ismaila IsholaCollege of Medicine, University of Lagos, Idi-araba, Lagos State, Nigeria.
Ashley RawlsUniversity of Florida Norman Fixel Institute for Neurological Diseases, Neurology Movement Disorders, Gainesville, USA.
Frank ImarhiagbeUniversity of Benin, Benin City, Edo State, Nigeria.ORCID 0000-0002-8518-2186
Shivika ChandraThe University of Texas Health Science Center at Houston, Houston, TX, USA.ORCID 0000-0002-9515-2837
Cyril EramehIrrua Specialist Teaching Hospital, Irrua, Edo State, Nigeria.ORCID 0000-0001-7783-2495
Vanessa HinsonMedical University of South Carolina, Charleston, SC, USA.ORCID 0009-0007-0677-1956
Naomi LouieMichael J. Fox Foundation for Parkinson's Research, Department of Clinical Research, New York, USA.ORCID 0009-0001-1104-8742
Ahmed IdowuObafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Osun State, Nigeria.ORCID 0000-0002-9072-9238
J SolleMichael J. Fox Foundation for Parkinson's Research, Department of Clinical Research, New York, USA.
Scott A NorrisWashington University in St. Louis, St. Louis, MO, USA.
Abdullahi IbrahimFederal University of Health Sciences Teaching Hospital, Azare, Bauchi State, Nigeria.
Camilla KilbaneUniversity Hospital in Cleveland Medical Center/Case Western Reserve University (UH).ORCID 0000-0003-2026-5375
Gauthaman SukumarDepartment of Anatomy, Physiology and Genetics, School of Medicine, Uniformed Services.
Lisa M ShulmanUniversity of Maryland, Baltimore, MD, USA.
Daniel EzuduemoihLagos University Teaching Hospital, Idi-araba, Lagos State, Nigeria.ORCID 0000-0003-0626-2426
Julia StaischOchsner Clinic Foundation, New Orleans, LA, USA.ORCID 0000-0001-7426-2693
Sarah BreauxOchsner Clinic Foundation, New Orleans, LA, USA.ORCID 0009-0008-6504-0915
Clifton DalgardHenry M. Jackson Foundation for the Advancement of Military Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.ORCID 0000-0003-2025-8239
Erin R FosterWashington University in St. Louis, St. Louis, MO, USA.
Abiodun BelloUniversity of Ilorin Teaching Hospital, Ilorin, Kwara State, Nigeria.ORCID 0000-0002-2078-6739
Andrew AmeriMedical University of South Carolina, Charleston, SC, USA.
Raquel RealDepartment of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London WC1N 3BG, UK.ORCID 0000-0001-8117-742X
Erica IkwenuLagos University Teaching Hospital, Idi-araba, Lagos State, Nigeria.
Huw R MorrisDepartment of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London WC1N 3BG, UK.ORCID 0000-0002-5473-3774
Roosevelt AnyanwuCollege of Medicine, University of Lagos, Idi-araba, Lagos State, Nigeria.ORCID 0000-0002-6748-9379
Erin Furr StimmingThe University of Texas Health Science Center at Houston, Houston, TX, USA.ORCID 0000-0003-2466-0831
Kimberley BillingsleyCenter for Alzheimer's and Related Dementias, National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0002-8003-4029
Wemimo AlaofinUniversity of Ilorin, Ilorin, Kwara State, Nigeria.ORCID 0009-0002-4260-4219
Pilar Alvarez JerezLaboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
Osigwe AgabiCollege of Medicine, University of Lagos, Idi-araba, Lagos State, Nigeria.ORCID 0000-0002-3084-6918
Dena G HernandezLaboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0002-0188-9927
Rufus AkinyemiNeuroscience and Ageing Research Unit, Institute for Advanced Medical Research and Training, College of Medicine, University of Ibadan, Ibadan, Oyo State, Nigeria.ORCID 0000-0001-5286-428X
Sampath ArepalliLaboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
Laksh MalikCenter for Alzheimer's and Related Dementias, National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0002-2498-146X
Raymond OwolabiFederal Medical Center, Owo, Ondo State, Nigeria.
Yakub NyandaitiUniversity of Maiduguri Teaching Hospital, Maiduguri, Borno State.ORCID 0000-0002-3922-6344
Hampton L LeonardCenter for Alzheimer's and Related Dementias, National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0003-2390-8110
Kolawole WahabUniversity of Ilorin, Ilorin, Kwara State, Nigeria.ORCID 0000-0002-2914-1953
Kathryn StepDepartment of Biomedical Sciences, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.ORCID 0000-0002-4054-7030
Oladunni AbiodunGeneral Hospital, Isolo, Lagos State, Nigeria.ORCID 0000-0001-7652-6752
Carlos F HernandezUniversidad del Desarrollo, Centro de Genética y Genómica, Facultad de Medicina Clínica Alemana, Santiago 7610658, Chile.
Fatima AbdulaiUniversity of Abuja Teaching Hospital, Gwagwalada, Federal Capital Territory, Nigeria.ORCID 0000-0002-9787-0656
Hirotaka IwakiCenter for Alzheimer's and Related Dementias, National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0002-8982-7885
Soraya BardienDepartment of Biomedical Sciences, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.ORCID 0000-0002-3508-3438
Christine KleinInstitute of Neurogenetics and Department of Neurology, University of Lübeck and University Hospital Schleswig-Holstein, Lübeck, Germany.
John HardyReta Lila Weston Institute, University College London Institute of Neurology, Queen Square, London, UK.
Henry HouldenDepartment of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK.ORCID 0000-0002-2866-7777
Kamalini Ghosh GalvelisParkinson's Foundation, NewYork, NY 10018, USA.ORCID 0009-0000-4178-0777
Mike A NallsCenter for Alzheimer's and Related Dementias, National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Nabila DahodwalaUniversity of Pennsylvania, Philadelphia, PA.ORCID 0000-0003-3659-0244
Whitley AamodtUniversity of Pennsylvania, Philadelphia, PA.ORCID 0000-0001-8130-2809
Emily HillUniversity of Cincinnati, Cincinnati, Ohio.
Alberto EspayUniversity of Cincinnati, Cincinnati, Ohio.ORCID 0000-0002-3389-136X
Stewart FactorEmory University, Atlanta, GA.ORCID 0000-0002-0449-973X
Chantale BransonMorehouse College, Atlanta, GA.ORCID 0000-0002-7217-6094
Cornelis BlauwendraatLaboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0001-9358-8111
Andrew B SingletonLaboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0001-5606-700X
Oluwadamilola OjoCollege of Medicine, University of Lagos, Idi-araba, Lagos State, Nigeria.ORCID 0000-0001-6461-2653
Lana M ChahineUniversity of Pittsburgh, 3471 Fifth Avenue, Pittsburgh, PA, 15213, USA.ORCID 0000-0003-2521-7196
Black and African American Connections to Parkinson’s Disease Study (BLAAC PD)
Nigeria Parkinson’s Disease Research Network (NPDRN)
Racial Disparities in Parkinson Disease (RaD-PD)
Global Parkinson’s Genetics Program (GP2)
Njideka OkubadejoCollege of Medicine, University of Lagos, Idi-araba, Lagos State, Nigeria.ORCID 0000-0003-2975-8803
Sara Bandres-CigaCenter for Alzheimer's and Related Dementias, National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0003-0056-1361
Funding
STRIDESOT2OD027852 · OD · FOUR POINTS TECHNOLOGY, LLC · PI Joel A Lipkin · 2018 to 2026
$255.6MTechnology to Empower Changes in Health (TECH) Network Participant Technologies CenterU24OD023176 · OD · SCRIPPS RESEARCH INSTITUTE, THE · PI TOPOL, ERIC JEFFREY · 2016 to 2022
$204.7MPrecision Medicine Initiative Cohort Program BiobankU24OD023121 · OD · MAYO CLINIC ROCHESTER · PI CEKANOVA, MARIA, CICEK, MINE · 2016 to 2024
$185.5MEnhancing All of Us Data Resources for Nutrition Precision Health: the All of Us Data and Research CenterU2COD023196 · OD · VANDERBILT UNIVERSITY MEDICAL CENTER · PI GLAZER, DAVID, HARRIS, PAUL A. · 2016 to 2022
$143.7MSTRIDES OT2OD027060 · OD · CARAHSOFT TECHNOLOGY CORPORATION · PI Terry Drinkwine · 2018 to 2026
$134.1MAdaptive Platform for Personalized EngagementU24OD023163 · OD · VIGNET, INC. · PI JAIN, PRADUMAN · 2017 to 2020
$102.6MUniversity of Arizona-Banner Health All of Us Research Program OT2OD026549 · OD · UNIVERSITY OF ARIZONA · PI MORENO, FRANCISCO A, REIMAN, ERIC MICHAEL · 2018 to 2023
$78.9MCalifornia Precision Medicine Research Program ConsortiumOT2OD026552 · OD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ANTON-CULVER, HODA A, OHNO-MACHADO, LUCILA · 2018 to 2023
$73.4MAll of Us PennsylvaniaOT2OD026554 · OD · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI REIS, STEVEN E, VISWESWARAN, SHYAM · 2018 to 2023
$72.1MNew York City Consortium for Precision MedicineOT2OD026556 · OD · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI BIER, LOUISE E, GHARAVI, ALI G · 2018 to 2023
$67.3MSouthEast Enrollment Center (SEEC) OT2OD026551 · OD · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI CARRASQUILLO, OLVEEN, COLON, VIVIAN · 2018 to 2023
$62.8MNIH STRIDES - Azure and Associated Services and Training.OT2OD032100 · OD · DELL FEDERAL SYSTEMS L.P. · PI Amy K HammondOdwyer, Erum Siddiqui · 2021 to 2026
$62.2MIntramural NIH HHS Z01 AG000949Intramural NIH HHS ZIA AG000949Intramural NIH HHS ZIA NS003154NIA NIH HHS K24 AG000949NIH HHS OT2 OD023205NIH HHS OT2 OD023206NIH HHS OT2 OD025276NIH HHS OT2 OD025277NIH HHS OT2 OD025315NIH HHS OT2 OD025337NIH HHS OT2 OD026548NIH HHS OT2 OD026549NIH HHS OT2 OD026550NIH HHS OT2 OD026551NIH HHS OT2 OD026552NIH HHS OT2 OD026553NIH HHS OT2 OD026554NIH HHS OT2 OD026555NIH HHS OT2 OD026556NIH HHS OT2 OD026557NIH HHS OT2 OD027060NIH HHS OT2 OD027852NIH HHS OT2 OD032100NIH HHS U24 OD023121NIH HHS U24 OD023163NIH HHS U24 OD023176NIH HHS U2C OD023196NINDS NIH HHS R01 NS125294
Abstract
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
Indexed as
African admixed ancestryAfrican ancestryBlack and African American populationclinical trialsdisease-causing mutationsgeneticsmonogenicParkinson’s diseaserare variants
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