Insights into ancestral diversity in Parkinson’s disease risk: a comparative assessment of polygenic risk scores
Saffie-Awad P. Grant S.M. Makarious M.B. Elsayed I. Sanyaolu A.O. Crea P.W. Schumacher Schuh A.F. Levine K.S. Vitale D. Koretsky M.J. Kim J. Peixoto Leal T. Periñán M.T. Dey S. Noyce A.J. Reyes-Palomares A. Rodriguez-Losada N. Foo J.N. Mohamed W. Heilbron K. Norcliffe-Kaufmann L. Wong C.D. Wilton P. Weldon C.H. Wang W. Wang X. Tung J.Y. Tran V. Tchakouté C.T. Tat S.A. Su Q.J. Shringarpure S. Shi J. Shelton J.F. Shastri A.J. Schumacher M. Schloetter M. Reynoso A. Poznik G.D. Petrakovitz A.A. O’Connell J. Noblin E.S. Nguyen D.T. Nandakumar P. Moreno M.E. Micheletti S.J. McIntyre M.H. McCreight J.C. Lowe M. Llamas B.A. Lin K.-H. Kwong A. Kukar K. Jiang Y. Jewett E.M. Hinds D.A. Hicks B. Hernandez A. Granka J.M. Freyman W. Fontanillas P. Fletez-Brant K. Fitch A. Filshtein T. Eriksson N. Elson S.L. Das S. Dhamija D. Partida G.C. Coker D. Cannon P. Bullis E. Bryc K. Bielenberg J. Bell R.K. Babalola E. Auton A. Aslibekyan S. Rizig M. Okubadejo N. Nalls M.A. Blauwendraat C. Singleton A. Leonard H. Atadzhanov M. Nguyen T. Nguyen D. Song Y. Sherer T. Beach T. Foroud T. Xie T. Lubbe S. Dumanis S. Chowdhury S. Walker R. Alcalay R. Albin R. Mencacci N.E. Louie N. Inca-Martinez M. Dean M. Kuhl M. Marsili L. Shulman L. Ruffrage L. Screven L. Chahine L.M. Marek K. Markopoulou K. Kieburtz K. Nuytemans K. Murphy K. Solle J.C. Shulman J. Jankovic J. Williamson J. Sarmiento I.J.K. Chen H. Iwaki H. Serrano G.E. Faghri F. Riley E. Shamim E. Hernandez D. Hall D. Wegel C. Comart C. Pantazis C.B. Cruchaga C. Jonas C. Fiske B. Casey B. Siddiqi B. Sobering A.K. O’Grady A. Espay A. Obese V. Jasaitye S. Stott S. Love S. Weil R. Kaiyrzhanov R. Lewis P.A. Okunoye O. Williams N. Wood N. Mok K.Y. Hardy J. Morris H.R. Houlden H. Stafford E.J. Grosset D. Bale C. Carroll C. Schapira A. Schrag A. Martínez-Carrasco A. Ertan S. Çakmak Ö.Ö. Genc G. Başak A.N. Ben Sassi S. Amouri R. Wu Y.-R. Wu S. Wu R.-M. Kung P.-J. Wu H.-C. Lin C.-H. Krack P. Zweier C. El-Sadig S. Pastor P. Beyer K. Hoenicka J. Alvarez I. Cubo E. Kim Y.J. Jeon B. Bardien S. Carr J. Amod F. Tan E.-K. Umair M. Mubarak B.A. Iakovenko E. Vinuela A. Rosales R. Doquenia M.L. Cornejo-Olivas M. Ur-Rehman S. Tan M. Pihlstrøm L. Aasly J.O. Ojo O. Pitcher T.L. Anderson T.J. Ojha R. Tserensodnom B. Reyes-Pérez P. Rodriguez-Violante M. Martinez-Ramirez D. Tay Y.W. Lim S.-Y. Azmin S. Murad N.A.A. Norlinah M.I. Ahmad-Annuar A. Tan A.H. Krüger R. Shambetova C. Kaishibayeva G. Karimova A. Shiraishi T. Hattori N. Funayama M. Schirinzi T. Avenali M. Parnetti L. Valente E.M. Quattrone A. Salari M. Borgohain R. Rajan R. Kukkle P.L. Pal P. Divya K.P. Kishore A. Zhou X. Chan P. Cheung N.Y.-F. Ip N. Chan G.H.-F. Medina A. Dardiotis E. Stamelou M. Stefanis L. Tarnanas I. Dagklis I. Hadjigeorgiou G. Xiromerisiou G. Akpalu A. Fang Z.-H. Gasser T. Groppa S. Sharma M. Lange L.M. Lohmann K. Junker J. Trinh J. Madoev H. Höglinger G. Hopfner F. Vollstedt E.-J. Klein C. Mollenhauer B. Illarionova A. Westenberger A. Corvol J.-C. Brice A. Zewde Y.Z. Kamel W.A. Salama M. Hernandez A. del Rio M.J. Orozco J. Arboleda G. Luo W. Chan P. Guo J. Shang H. Tang B. Chana P. Olguin P. Bustamante M.L. Miranda M. Galleguillos B.P. Fon T. Monchi O. Fon E.A. Camargos S. Tumas V. Rieder C. Zimprich A. Koks S. Rentería M.E. Ellis M. Kumar K. Hunter J. Shepherd C.E. Tavadyan Z. Khachatryan S. Kauffman M. Gatto E.M. Mata I.F. Bandres-Ciga S.
December 2025Nature Research
npj Parkinsons Disease
2025#11Issue 1
Risk prediction models play a crucial role in advancing healthcare by enabling early detection and supporting personalized medicine. Nonetheless, polygenic risk scores (PRS) for Parkinson’s disease (PD) have not been extensively studied across diverse populations, contributing to health disparities. In this study, we constructed 105 PRS using individual-level data from seven ancestries and compared two different models. Model 1 was based on the cumulative effect of 90 known European PD risk variants, weighted by summary statistics from four independent ancestries (European, East Asian, Latino/Admixed American, and African/Admixed). Model 2 leveraged multi-ancestry summary statistics using a p-value thresholding approach to improve prediction across diverse populations. Our findings provide a comprehensive assessment of PRS performance across ancestries and highlight the limitations of a “one-size-fits-all” approach to genetic risk prediction. We observed variability in predictive performance between models, underscoring the need for larger sample sizes and ancestry-specific approaches to enhance accuracy. These results establish a foundation for future research aimed at improving generalizability in genetic risk prediction for PD.
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Programa de Pós-Graduação em Ciências Médicas, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
Centro de Trastornos del Movimiento (CETRAM), Santiago, Chile
Clínica Santa María, Santiago, Chile
Centre for Alzheimer’s and Related Dementias. National Institute on Aging, National Institutes of Health, Bethesda, MD, United States
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, United States
Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, United Kingdom
Faculty of Pharmacy, University of Gezira, Wadmadani, Sudan
Department of Anatomy, College of Medicine, University of Lagos, Lagos, Nigeria
Serviço de Neurologia, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
Departamento de Farmacologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
DataTecnica LLC, Washington, DC, United States
Genomic Medicine, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, United States
Unidad de Trastornos del Movimiento, Servicio de Neurología y Neurofisiología Clínica, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain
Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
Preventive Neurology Unit, Wolfson Institute of Population Health, Queen Mary University of London, London, United Kingdom
Department of Molecular Biology and Biochemistry, Faculty of Sciences, University of Málaga, Málaga, Spain
Faculty of Education Sciences, University of Málaga, Málaga, Spain
Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Singapore, Singapore
Laboratory of Neurogenetics, Genome Institute of Singapore, A*STAR, Singapore, Singapore
Neuroscience Unit, Clinical Pharmacology Dept, Menoufia Medical School, Shebeen El-Kom, Egypt
23andMe Inc., Sunnyvale, CA, United States
Department of Medicine, College of Medicine, University of Lagos, Lagos, Nigeria
German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany
Sanatorio de la Trinidad Mitre-INEBA, Buenos Aires, Argentina
Hospital JM Ramos Mejia, Buenos Aires, Argentina
Somnus Neurology Clinic, Yerevan, Armenia
Neuroscience Research Australia, Sydney, NSW, Australia
ANZAC Research Institute, Concord, NSW, Australia
Garvan Institute of Medical Research and Concord Repatriation General Hospital, Darlinghurst, NSW, Australia
Concord Hospital, Concord, NSW, Australia
QIMR Berghofer Medical Research Institute, Herston, QLD, Australia
Murdoch University, Perth, WA, Australia
Medical University of Vienna, Vienna, Austria
Universidade Federal do Rio Grande do Sul / Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
University of São Paulo, São Paulo, Brazil
Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
McGill University, Montreal, QC, Canada
Universidad de Chile, Santiago, Chile
Fundación Diagnosis, Santiago, Chile
Faculty of Medicine, Universidad de Chile, Santiago, Chile
CETRAM, Santiago, Chile
Central South University, Changsha, China
West China Hospital, Sichuan University, Chengdu, China
Xiangya Hospital, Central South University, Changsha, China
Capital Medical University, Beijing, China
Zhejiang University, Hangzhou, China
Universidad Nacional de Colombia, Bogotá, Colombia
Fundación Valle del Lili, Santiago de Cali, Colombia
University of Antioquia, Medellín, Colombia
University of Costa Rica, San José, Costa Rica
The American University in Cairo, Cairo, Egypt
Beni-Suef University, Beni Suef, Egypt
Addis Ababa University, Addis Ababa, Ethiopia
Paris Brain Institute, Paris, France
Sorbonne Université, Paris, France
University of Lübeck, Lübeck, Germany
Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Göttingen, Germany
University Medical Center Göttingen, Göttingen, Germany
University Hospital LMU Munich, Munich, Germany
Hannover Medical School, Hannover, Germany
University of Lübeck and University Medical Center Schleswig-Holstein, Lübeck, Germany
University of Tübingen, Tübingen, Germany
The German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany
University of Ghana Medical School, Accra, Ghana
University of Thessaly, Larissa, Greece
Aristotle University of Thessaloniki, Thessaloniki, Greece
Ionian University, Corfu, Greece
Biomedical Research Foundation of the Academy of Athens, Athens, Greece
Diagnostic and Therapeutic Centre HYGEIA Hospital, Marousi, Greece
Hospital San Felipe, Tegucigalpa, Honduras
Queen Elizabeth Hospital, Kowloon, Hong Kong
The Hong Kong University of Science and Technology, Kowloon, Hong Kong
Aster Medcity, Kochi, India
Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, India
National Institute of Mental Health & Neurosciences (NIMHANS), Bengaluru, India
Manipal Hospital, Delhi, India
All India Institute of Medical Sciences, Delhi, India
Nizam’s Institute of Medical Sciences, Hyderabad, India
Shahid Beheshti University of Medical Sciences, Tehran, Iran
Magna Græcia University of Catanzaro, Catanzaro, Italy
University of Pavia, Pavia, Italy
University of Perugia, Perugia, Italy
University of Rome Tor Vergata, Rome, Italy
Juntendo University, Tokyo, Japan
Juntendo University Faculty of Medicine, Tokyo, Japan
Jikei University School of Medicine, Tokyo, Japan
Institute of Neurology and Neurorehabilitation, Almaty, Kazakhstan
Kyrgyz State Medical Academy, Bishkek, Kyrgyzstan
Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Belvaux, Luxembourg
University of Malaya, Kuala Lumpur, Malaysia
Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
UKM Medical Molecular Biology Institute (UMBI), Kuala Lumpur, Malaysia
Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia
Tecnológico de Monterrey, Monterrey, Mexico
Instituto Nacional de Neurología y Neurocirugía, Mexico City, Mexico
Universidad Nacional Autónoma de México, Mexico City, Mexico
Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia
Tribhuvan University, Kirtipur, Nepal
University of Otago, Christchurch, New Zealand
University of Otago, Dunedin, New Zealand
College of Medicine, University of Lagos, Lagos, Nigeria
Norwegian University of Science and Technology, Trondheim, Norway
Oslo University Hospital, Oslo, Norway
University of Science and Technology Bannu, Khyber Pakhtunkhwa, Pakistan
Instituto Nacional de Ciencias Neurológicas, Lima, Peru
Metropolitan Medical Center, Manila, Philippines
University of Puerto Rico, San Juan, Puerto Rico
Research Center of Neurology, Moscow, Russian Federation
King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
King Abdullah International Medical Research Center, Jeddah, Saudi Arabia
National Neuroscience Institute, Singapore, Singapore
University of KwaZulu-Natal, Durban, South Africa
University of Stellenbosch, Stellenbosch, South Africa
Stellenbosch University, Stellenbosch, South Africa
Seoul National University Hospital, Seoul, South Korea
Yongin Severance Hospital, Seoul, South Korea
Hospital Universitario de Burgos, Burgos, Spain
University Hospital Mutua Terrassa, Barcelona, Spain
Institut de Recerca Sant Joan de Déu, Barcelona, Spain
Research Institute Germans Trias i Pujol, Badalona, Spain
University Hospital Germans Trias i Pujol, Badalona, Spain
Faculty of Medicine, University of Khartoum, Khartoum, Sudan
Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
National Taiwan University Hospital, Taipei City, Taiwan
Chang Gung Memorial Hospital, Taoyuan City, Taiwan
National Taiwan University, Taipei City, Taiwan
Chang Gung University, Taoyuan City, Taiwan
National Institute Mongi Ben Hamida of Neurology, Tunis, Tunisia
Mongi Ben Hmida National Institute of Neurology, Tunis, Tunisia
Koç University, Istanbul, Turkey
Şişli Etfal Training and Research Hospital, Istanbul, Turkey
University College London, London, United Kingdom
University of Plymouth, Plymouth, United Kingdom
Parkinson’s UK, London, United Kingdom
University of Glasgow, Glasgow, United Kingdom
Queen Mary University of London, London, United Kingdom
Cardiff University, Cardiff, United Kingdom
Royal Veterinary College, University of London, London, United Kingdom
University of Bristol, Bristol, United Kingdom
Cure Parkinson’s Trust, London, United Kingdom
University of Cincinnati, Cincinnati, OH, United States
The Michael J. Fox Foundation for Parkinson’s Research, New York, NY, United States
Augusta University / University of Georgia Medical Partnership, Athens, GA, United States
Mid-Atlantic Permanente Medical Group, Rockville, MD, United States
Washington University in St. Louis, St. Louis, MO, United States
National Institutes of Health, Bethesda, MD, United States
Indiana University, Bloomington, IN, United States
Rush University Medical Center, Chicago, IL, United States
Kaiser Permanente, Oakland, CA, United States
Aligning Science Across Parkinson’s, Washington, DC, United States
Banner Sun Health Research Institute, Sun City, AZ, United States
Michigan State University, East Lansing, MI, United States
Northwestern University, Chicago, IL, United States
Baylor College of Medicine, Houston, TX, United States
Baylor College of Medicine/Texas Children’s Hospital, Houston, TX, United States
University of Miami Miller School of Medicine, Miami, FL, United States
Beth Israel Deaconess Medical Center, Boston, MA, United States
NorthShore University HealthSystem, Evanston, IL, United States
Institute for Neurodegenerative Disorders, New Haven, CT, United States
University of Pittsburgh, Pittsburgh, PA, United States
University of Alabama at Birmingham, Birmingham, AL, United States
University of Maryland School of Medicine, Baltimore, MD, United States
University of Michigan, Ann Arbor, MI, United States
Columbia University Irving Medical Center, New York, NY, United States
James J. Peters VA Medical Center, Bronx, NY, United States
University of Chicago, Chicago, IL, United States
Indiana University School of Medicine, Indianapolis, IN, United States
Hue University, Huế, Viet Nam
University of Zambia, Lusaka, Zambia
Programa de Pós-Graduação em Ciências Médicas
Centro de Trastornos del Movimiento (CETRAM)
Clínica Santa María
Centre for Alzheimer’s and Related Dementias. National Institute on Aging
Laboratory of Neurogenetics
Department of Neuromuscular Diseases
Faculty of Pharmacy
Department of Anatomy
Serviço de Neurologia
Departamento de Farmacologia
DataTecnica LLC
Genomic Medicine
Unidad de Trastornos del Movimiento
Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED)
Preventive Neurology Unit
Department of Molecular Biology and Biochemistry
Faculty of Education Sciences
Lee Kong Chian School of Medicine
Laboratory of Neurogenetics
Neuroscience Unit
23andMe Inc.
Department of Medicine
German Center for Neurodegenerative Diseases (DZNE)
Sanatorio de la Trinidad Mitre-INEBA
Hospital JM Ramos Mejia
Somnus Neurology Clinic
Neuroscience Research Australia
ANZAC Research Institute
Garvan Institute of Medical Research and Concord Repatriation General Hospital
Concord Hospital
QIMR Berghofer Medical Research Institute
Murdoch University
Medical University of Vienna
Universidade Federal do Rio Grande do Sul / Hospital de Clínicas de Porto Alegre
University of São Paulo
Universidade Federal de Minas Gerais
McGill University
Universidad de Chile
Fundación Diagnosis
Faculty of Medicine
CETRAM
Central South University
West China Hospital
Xiangya Hospital
Capital Medical University
Zhejiang University
Universidad Nacional de Colombia
Fundación Valle del Lili
University of Antioquia
University of Costa Rica
The American University in Cairo
Beni-Suef University
Addis Ababa University
Paris Brain Institute
Sorbonne Université
University of Lübeck
Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE)
University Medical Center Göttingen
University Hospital LMU Munich
Hannover Medical School
University of Lübeck and University Medical Center Schleswig-Holstein
University of Tübingen
The German Center for Neurodegenerative Diseases (DZNE)
University of Ghana Medical School
University of Thessaly
Aristotle University of Thessaloniki
Ionian University
Biomedical Research Foundation of the Academy of Athens
Diagnostic and Therapeutic Centre HYGEIA Hospital
Hospital San Felipe
Queen Elizabeth Hospital
The Hong Kong University of Science and Technology
Aster Medcity
Sree Chitra Tirunal Institute for Medical Sciences and Technology
National Institute of Mental Health & Neurosciences (NIMHANS)
Manipal Hospital
All India Institute of Medical Sciences
Nizam’s Institute of Medical Sciences
Shahid Beheshti University of Medical Sciences
Magna Græcia University of Catanzaro
University of Pavia
University of Perugia
University of Rome Tor Vergata
Juntendo University
Juntendo University Faculty of Medicine
Jikei University School of Medicine
Institute of Neurology and Neurorehabilitation
Kyrgyz State Medical Academy
Luxembourg Centre for Systems Biomedicine
University of Malaya
Universiti Kebangsaan Malaysia
UKM Medical Molecular Biology Institute (UMBI)
Universiti Kebangsaan Malaysia Medical Centre
Tecnológico de Monterrey
Instituto Nacional de Neurología y Neurocirugía
Universidad Nacional Autónoma de México
Mongolian National University of Medical Sciences
Tribhuvan University
University of Otago
University of Otago
College of Medicine
Norwegian University of Science and Technology
Oslo University Hospital
University of Science and Technology Bannu
Instituto Nacional de Ciencias Neurológicas
Metropolitan Medical Center
University of Puerto Rico
Research Center of Neurology
King Faisal Specialist Hospital and Research Center
King Abdullah International Medical Research Center
National Neuroscience Institute
University of KwaZulu-Natal
University of Stellenbosch
Stellenbosch University
Seoul National University Hospital
Yongin Severance Hospital
Hospital Universitario de Burgos
University Hospital Mutua Terrassa
Institut de Recerca Sant Joan de Déu
Research Institute Germans Trias i Pujol
University Hospital Germans Trias i Pujol
Faculty of Medicine
Inselspital
National Taiwan University Hospital
Chang Gung Memorial Hospital
National Taiwan University
Chang Gung University
National Institute Mongi Ben Hamida of Neurology
Mongi Ben Hmida National Institute of Neurology
Koç University
Şişli Etfal Training and Research Hospital
University College London
University of Plymouth
Parkinson’s UK
University of Glasgow
Queen Mary University of London
Cardiff University
Royal Veterinary College
University of Bristol
Cure Parkinson’s Trust
University of Cincinnati
The Michael J. Fox Foundation for Parkinson’s Research
Augusta University / University of Georgia Medical Partnership
Mid-Atlantic Permanente Medical Group
Washington University in St. Louis
National Institutes of Health
Indiana University
Rush University Medical Center
Kaiser Permanente
Aligning Science Across Parkinson’s
Banner Sun Health Research Institute
Michigan State University
Northwestern University
Baylor College of Medicine
Baylor College of Medicine/Texas Children’s Hospital
University of Miami Miller School of Medicine
Beth Israel Deaconess Medical Center
NorthShore University HealthSystem
Institute for Neurodegenerative Disorders
University of Pittsburgh
University of Alabama at Birmingham
University of Maryland School of Medicine
University of Michigan
Columbia University Irving Medical Center
James J. Peters VA Medical Center
University of Chicago
Indiana University School of Medicine
Hue University
University of Zambia
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