A polygenic score (PGS) for Alzheimer's disease (AD) was derived recently from data on genome-wide significant loci in European ancestry populations. We applied this PGS to populations in 17 European countries and observed a consistent association with the AD risk, age at onset and cerebrospinal fluid levels of AD biomarkers, independently of apolipoprotein E locus (APOE). This PGS was also associated with the AD risk in many other populations of diverse ancestries. A cross-ancestry polygenic risk score improved the association with the AD risk in most of the multiancestry populations tested when the APOE region was included. Finally, we found that the PGS/polygenic risk score captured AD-specific information because the association weakened as the diagnosis was broadened. In conclusion, a simple PGS captures the AD-specific genetic information that is common to populations of different ancestries, although studies of more diverse populations are still needed to better characterize the genetics of AD.

1st Department of Neurology Aiginition Hospital National and Kapodistrian University of Athens Medical School Athens Greece

1st Department of Neurology Medical School Aristotle University of Thessaloniki Thessaloniki Greece

ACE Alzheimer Center Barcelona Universitat Internacional de Catalunya Barcelona Spain

Alzheimer Center Department of Neurology Erasmus MR Rotterdam the Netherlands

Alzheimer Research Center and Memory Clinic Andalusian Institute for Neuroscience Málaga Spain

Alzheimer's Centre Reina Sofia CIEN Foundation ISCIII Madrid Spain

Alzheimer's Disease and Other Cognitive Disorders Unit Service of Neurology Hospital Clínic of Barcelona Institut d'Investigacions Biomèdiques August Pi i Sunyer University of Barcelona Barcelona Spain

Behavioral Sciences Division National Center for PTSD VA Boston Healthcare System Boston MA USA

Biomedica Research Group Centro de Estudios Clínicos Santiago Chile

Biomedical Genetics Department of Medicine Boston University Chobanian and Avedisian School of Medicine Boston MA USA

BK FOUR Department of Integrative Biological Sciences Chosun University Gwangju Republic of Korea

Bordeaux Population Health Research Center INSERM Bordeaux UMR 1219 Bordeaux France

Bordeaux Population Health Research Center Inserm UMR 1219 Université Bordeaux ISPED CIC 1401 EC Université Bordeaux Bordeaux France

Bordeaux Population Health Research Center University Bordeaux Inserm Bordeaux France

Boston University and the NHLBI's Framingham Heart Study Boston MA USA

Center for Alzheimer's and Related Dementias NIH Bethesda MD USA

Center for Behavior Genetics of Aging University of California San Diego La Jolla CA USA

Center for Military Precision Health The American Genome Center Uniformed Services University of the Health Sciences Bethesda MD USA

Center of Excellence for Stress and Mental Health VA San Diego Healthcare System San Diego CA USA

Center of Neuropsychiatry and Behavior Neurology School of Medicine University of Buenos Aires Buenos Aires Argentina

Centre for Healthy Brain Ageing School of Psychiatry Faculty of Medicine University of New South Wales Sydney New South Wales Australia

Centre for Memory Disturbances Laboratory of Clinical Neurochemistry Section of Neurology University of Perugia Perugia Italy

Centre for Neuropsychiatric Genetics and Genomics School of Medicine Cardiff University Cardiff UK

Centre for Precision Health Edith Cowan University Perth Western Australia Australia

Centro de Biología Molecular Severo Ochoa Madrid Spain

CHU Clinical and Research Memory Research Centre of Distalz Lille France Université Lille Inserm 1171 Paris France

CHU de Bordeaux Pole Santé Publique Bordeaux France

CIBERNED Network Center for Biomedical Research in Neurodegenerative Diseases National Institute of Health Carlos 3 Madrid Spain

Clinic of Neurology UH Alexandrovska Medical University Sofia Bulgaria

Cluster of Excellence Cellular Stress Responses in Aging Associated Diseases University of Cologne Cologne Germany

Collaborative Genomics and Translation Group School of Medical and Health Sciences Edith Cowan University Perth Western Australia Australia

Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Disease University of Cologne Cologne Germany

Complex Genetics of Alzheimer's Disease Group VIB Center for Molecular Neurology VIB Antwerp Belgium

Curtin Health Innovation Research Institute Curtin University Perth Western Australia Australia

DataTecnica LLC Washington DC USA

Deaprtment of Clinical and Experimental Sciences University of Brescia Italy Brescia Italy

Departamento de Psiquiatría y Salud Mental Campus Oriente Facultad de MedicinaUniversidad de Chile Santiago Chile

Department for Neurodegenerative Diseases and Geriatric Psychiatry University Hospital Bonn Bonn Germany

Department of Anatomy Physiology and Genetics Uniformed Services University of the Health Sciences Bethesda MD USA

Department of Biochemistry and Structural Biology University of Texas Health Science Center San Antonio TX USA

Department of Biomedical Science Chosun University Gwangju Republic of Korea

Department of Biomedical Sciences University of Antwerp Antwerp Belgium

Department of Biomedical Sciences University of Cagliari Cagliari Italy

Department of Biomedical Surgical and Dental Sciences University of Milan Milan Italy

Department of Biostatistics Boston University School of Public Health Boston MA USA

Department of Biostatistics University of Washington Seattle WA USA

Department of Cardiovascular Sciences University of Leicester Leicester UK

Department of Child and Adolescent Psychiatry and Psychotherapy University Hospital of Psychiatry Zurich University of Zurich Zurich Switzerland

Department of Clinical Biochemistry Copenhagen University Hospital Rigshospitalet Copenhagen Denmark

Department of Clinical Genetics VU University Medical Centre Amsterdam the Netherlands

Department of Clinical Medicine Federal University of Minas Gerais Belo Horizonte Minas Geraes Brazil

Department of Clinical Medicine University of Copenhagen Copenhagen Denmark

Department of Clinical Sciences and Community Health University of Milan Milan Italy

Department of Complex Trait Genetics Center for Neurogenomics and Cognitive Research Amsterdam Neuroscience Vrije University Amsterdam the Netherlands

Department of Continuity of Care and Frailty ASST Spedali Civili Brescia Brescia Italy

Department of Epidemiology and Biostatistics Case Western Reserve University Cleveland OH USA

Department of Epidemiology Boston University Boston MA USA

Department of Epidemiology ErasmusMC Rotterdam the Netherlands

Department of Genetics and CNR MAJ Université Rouen Normandie Normandie Université Inserm U1245 and CHU Rouen Rouen France

Department of Genome Sciences University of Washington Seattle WA USA

Department of Geriatric Medicine Oslo University Hospital Oslo Norway

Department of Geriatric Psychiatry Central Institute for Mental Health Mannheim Faculty Mannheim University of Heidelberg Heidelberg Germany

Department of Geriatric Psychiatry University Hospital of Psychiatry Zürich Zurich Switzerland

Department of Geriatrics Radboud University Medical Center Research Institute for Medical Innovation Rotterdam the Netherlands

Department of Hematology and Stem Cell Transplant Vito Fazzi Hospital Lecce Italy

Department of Medical and Molecular Genetics Indiana University Indianapolis IN USA

Department of Medicine Boston University Boston MA USA

Department of Medicine University of Washington Seattle WA USA

Department of Neurobiology Care Sciences and Society Aging Research Center Karolinska Institutet and Stockholm University Stockholm Sweden

Department of Neurobiology Care Sciences and Society Division of Clinical Geriatrics Karolinska Institutet Stockholm Sweden

Department of Neurology Alzheimer Center Amsterdam Amsterdam Neuroscience Vrije Universiteit Amsterdam Amsterdam UMC Amsterdam the Netherlands

Department of Neurology Amitié Hospital Bangui Central African Republic

Department of Neurology and Neurological Sciences Stanford University School of Medicine Stanford CA USA

Department of Neurology and Psychiatry Clínica Alemana Santiago Chile

Department of Neurology Bordeaux University Hospital Bordeaux France

Department of Neurology Boston University Boston MA USA

Department of Neurology Boston University School of Medicine Boston MA USA

Department of Neurology Brazzaville University Hospital Brazzaville Republic of Congo

Department of Neurology Columbia University New York NY USA

Department of Neurology Hospital Universitario Donostia San Sebastian Spain

Department of Neurology Memory and Aging Center Weill Institute for Neurosciences University of California San Francisco CA USA

Department of Neurology Memory Clinic Charles University 2nd Faculty of Medicine and Motol University Hospital Brno Czech Republic

Department of Neurology Taub Institute on Alzheimer's Disease and the Aging Brain Columbia University New York NY USA

Department of Neurology UH Alexandrovska Medical University Sofia Bulgaria

Department of Neurology Unit of Neurodegenerative Diseases University Hospital Germans Trias i Pujol Badalona Spain

Department of Neuroscience Mount Sinai School of Medicine New York NY USA

Department of Neuroscience Psychology Drug Research and Child Health University of Florence Florence Italy

Department of Neuroscience Rita Levi Montalcini University of Torino Turin Italy

Department of Neuroscience Università Cattolica del Sacro Cuore Rome Italy

Department of Old Age Psychiatry and Cognitive Disorders University Hospital Bonn University of Bonn Bonn Germany

Department of Ophthalmology Boston University Boston MA USA

Department of Pathology and Laboratory Medicine Penn Neurodegeneration Genomics Center University of Pennsylvania Perelman School of Medicine Philadelphia PA USA

Department of Population Health Sciences University of Texas Health Science Center San Antonio TX USA

Department of Psychiatry and Comprehensive Center of Neuroscience and Mental Health Medical University of Vienna Vienna Austria

Department of Psychiatry and Neuropsychology Maastricht University Alzheimer Center Limburg Maastricht the Netherlands

Department of Psychiatry and Psychotherapy Center for Cognitive Disorders Technical University of Munich School of Medicine Munich Germany

Department of Psychiatry and Psychotherapy Faculty of Medicine and University Hospital Cologne Division of Neurogenetics and Molecular Psychiatry University of Cologne Cologne Germany

Department of Psychiatry and Psychotherapy Faculty of Medicine and University Hospital Cologne University of Cologne Cologne Germany

Department of Psychiatry and Psychotherapy LVR University Hospital Essen Medical Faculty of the University of Duisburg Essen Essen Germany

Department of Psychiatry and Psychotherapy University Medical Center Goettingen Goettingen Germany

Department of Psychiatry Boston University Chobanian and Avedisian School of Medicine Boston MA USA

Department of Psychiatry Federal University of Minas Gerais Belo Horizonte Minas Geraes Brazil

Department of Psychiatry Old Age Psychiatry Lausanne University Hospital Lausanne Switzerland

Department of Psychiatry Psychosomatics and Psychotherapy Center of Mental Health University Hospital of Würzburg Würzburg Germany

Department of Psychiatry University of California San Diego La Jolla CA USA

Department of Psychiatry Washington University School of Medicine St Louis MO USA

Department of Public Health and Caring Sciences Geriatrics Uppsala University Uppsala Sweden

Department of Public Health and Carins Sciences Geriatrics Uppsala University Uppsala Sweden

Department of Radiology and Biomedical Imaging University of California San Francisco CA USA

Department of Radiology ErasmusMC Rotterdam the Netherlands

Department of Radiology Indiana University Indianapolis IN USA

Department of Surgery Federal University of Minas Gerais Belo Horizonte Minas Geraes Brazil

Departments of Medicine and Laboratory Medicine and Pathobiology Tanz Centre for Research in Neurodegenerative Diseases University of Toronto Toronto Ontario Canada

Depatamento de Bioquímica Médica Biología Molecular e Inmunología Facultad de Medicina Universidad de Sevilla Sevilla Spain

Depatamento de Especialidades Quirúrgicas Bioquímica e Inmunología Facultad de Medicina Universidad de Málaga Málaga Spain

Depatment of Neurology Columbia University New York NY USA

Division of Aging Brigham and Women's Hospital Harvard Medical School Boston MA USA

Division of Life Science State Key Laboratory of Molecular Neuroscience Molecular Neuroscience Center The Hong Kong University of Science and Technology Kowloon China

Division of Mental Health and Addiction NORMENT Centre Oslo University Hospital Oslo Norway

Division of Neurogenetics and Molecular Psychiatry Department of Psychiatry and Psychotherapy University of Cologne Medical Faculty Cologne Germany

Division of Psychological Medicine and Clinical Neuroscience School of Medicine Cardiff University Cardiff UK

Dr John T Macdonald Foundation Department of Human Genetics University of Miami Miami FL USA

EpiMaCT Epidemiology of chronic diseases in tropical zone Inserm U1094 IRD UMR270 Université Limoges CHU Limoges Institute of Epidemiology and Tropical Neurology OmegaHealth Limoges France

Faculty of Medicine University of Lisbon Lisbon Portugal

Faculty of Medicine University of Oslo Oslo Norway

Fondazione IRCCS Istituto Neurologico Carlo Besta Milan Italy

Genetics of Neurodegenerative Diseases Unit IIB Sant Pau Barcelona Spain

Geriatrics Section Clinical Hospital University of Chile Santiago de Chile Chile

Geriatrics Service of the University Hospital Federal University of Minas Gerais Belo Horizonte Minas Geraes Brazil

German Center for Neurodegenerative Diseases Berlin Germany

German Center for Neurodegenerative Diseases Bonn Germany

German Center for Neurodegenerative Diseases Goettingen Germany

German Center for Neurodegenerative Diseases Magdeburg Germany

German Center for Neurodegenerative Diseases Munich Germany

Geroscience Center for Brain Health and Metabolism Santiago Chile

Gertrude H Sergievsky Center Columbia University New York NY USA

Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases San Antonio TX USA

Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases University of Texas Health Sciences Center San Antonio TX USA

Graduate School of Frontier Science University of Tokyo Tokyo Japan

Guangdong Provincial Key Laboratory of Brain Science Disease and Drug Development HKUST Shenzhen Research InstituteShenzhen Hong Kong Institute of Brain Science Shenzhen China

Gwangju Alzheimer's and Related Dementia Cohort Research Center Chosun University Gwangju Republic of Korea

High Institute of Biotechnology University of Monastir Monastir Tunisia

Hong Kong Center for Neurodegenerative Diseases Hong Kong China

Hôpital Broca Université de Paris EA 4468 APHP Paris France

Hospital Interzonal General de Agudos Eva Perón Buenos Aires Argentina

Institut de Recerca Biomedica de Lleida Lleida Spain

Institut du Cerveau Paris Brain Institute ICM Paris France

Institut du Cerveau Paris Brain Institute ICM Sorbonne Université CNRS APHP Hôpital de La Pitié Salpêtrière Inserm Paris France

Institute for Regenerative Medicine University of Zürich Zurich Switzerland

Institute for Stroke and Dementia Research University Hospital LMU Munich Munich Germany

Institute for Urban Public Health University Hospital Essen University Duisburg Essen Essen Germany

Institute of Biomedicine University of Eastern Finland Kuopio Finland

Institute of Clinical Medicine Neurology University of Eastern Finland Kuopio Finland

Institute of Clinical Medicine University of Oslo Oslo Norway

Institute of Cognitive Neurology and Dementia Research Otto von Guericke University Magdeburg Germany

Institute of Gerontology and Geriatrics Department of Medicine and Surgery University of Perugia Perugia Italy

Institute of Human Genetics University of Bonn School of Medicine and University Hospital Bonn Bonn Germany

Institute of Neurology Catholic University of the Sacred Heart Rome Italy

Institute of Psychiatry and Psychotherapy Charité Universitätsmedizin Berlin corporate member of Freie Universität Berlin Humboldt Universität zu Berlin and Berlin Institute of Health Berlin Germany

Institute of Social Medicine Occupational Health and Public Health University of Leipzig Leipzig Germany

Instituto de Biomedicina de Sevilla IBiS Hospital Universitario Virgen de Valme Sevilla Spain

Instituto de Investigacion Sanitaria 'Hospital la Paz' Madrid Spain

Instituto de Investigación Sanitaria del Principado de Asturias Oviedo Spain

Instituto Nacional de Geriatría Santiago Chile

Interdisciplinary Department of Medicine Geriatric Medicine and Memory Unit University of Bari A Moro Bari Italy

International Clinical Research Center St Anne's University Hospital Brno Brno Czech Republic

Interuniversity Center for Healthy Aging RED21993 Santiago de Chile Chile

IRCCS Fondazione Don Carlo Gnocchi Florence Italy

Krembil Brain Institute University Health Network Toronto Ontario Canada

Laboratorio de Genética Hospital Universitario Central de Asturias Oviedo Spain

Laboratory of Brain Aging and Neurodegeneration Fundacion Instituto Leloir IIBBA Buenos Aires Argentina

Laboratory of Genetics Immunology and Human Pathology Faculty of Science of Tunis University of Tunis El Manar Tunis Tunisia

Laboratory of Neurogenetics NIH Bethesda MD USA

Laboratory of Neuropsychiatry IRCCS Santa Lucia Foundation Rome Italy

Latin American Institute for Brain Health Universidad Adolfo Ibanez Santiago Chile

Massachusetts Veterans Epidemiology Research and Information Center VA Boston Healthcare System Boston MA USA

Medical Science Department iBiMED Aveiro Portugal

Memory and Neuropsychiatric Center Neurology Department Hospital del Salvador y Facultad de Medicina Universidad de Chile Santiago Chile

Molecular Markers Laboratory IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli Brescia Italy

Munich Cluster for Systems Neurology Munich Germany

National Institute of Science and Technology Neurotec R Federal University of Minas Geraes Belo Horizonte Minas Geraes Brazil

Neurodegenerative Diseases Unit Fondazione IRCCS Ca' Granda Ospedale Policlinico Milan Italy

NeuroGenomics and Informatics Center Washington University School of Medicine St Louis MO USA

Neurological Tissue Bank Biobanc Hospital Clinic FRCB IDIBAPS Barcelona Spain

Neurology Department Alzheimer's Disease and Other Cognitive Disorders Unit Hospital Clinic Barcelona Spain

Neurology IRCCS San Gerardo dei Tintori Monza and University of Milano Bicocca Milano Italy

Neurology Service Hospital del Salvador Santiago Chile

Neurology Service Marqués de Valdecilla University Hospital Santander Spain

Neurology Unit IRCCS Fondazione Policlinico Universitario A Gemelli Rome Italy

Neuroscience and Cell Death Research Groups Medical School and Genetic Institute Universidad Nacional de Colombia Bogota Colombia

Neuroscience Center Zurich University of Zurich and ETH Zurich Zurich Switzerland

Neurosciences Area Instituto Biogipuzkoa San Sebastian Spain

Niigata University Brain Research Institute Niigata Japan

Norwegian Centre for Ageing and Health Vestfold Hospital Trust Tønsberg Norway

Nuffield Department of Population Health Oxford University Oxford UK

Past Director Dementia Unit University of Parma Parma Italy

Pharmaceutical Sciences and Pharmacogenomics Graduate Program University of California San Francisco CA USA

Psychiatry Service of the University Hospital Federal University of Minas Gerais Belo Horizonte Minas Geraes Brazil

Public Health Nutrition Unit Institute of Nutrition and Food Technology University of Chile Santiago de Chile Chile

Research Center National Center for Geriatrics and Gerontology Obu Japan

Studies in Neuroscience and Complex Systems Unit CONICET HEC UNAJ Buenos Aires Argentina

Studies in Neuroscience and Complex Systems Unit CONICET HEC UNAJ Santiago Chile

The Germans Trias i Pujol Research Institute Badalona Spain

The John P Hussman Institute for Human Genomics University of Miami Miami FL USA

Translational Health Sciences Bristol Medical School University of Bristol Bristol UK

U1167 RID AGE facteurs de risque et déterminants moléculaires des maladies liées au vieillissement Université Lille Inserm CHU Lille Institut Pasteur de Lille Lille France

UK Dementia Research Institute Cardiff University Cardiff UK

Unidad de Investigación Epidemiológica y en Servicios de Salud Área Envejecimiento Centro Médico Nacional Siglo XXI Instituto Mexicano del Seguro Social Mexico City Mexico

Unidad de Trastornos del Movimiento Servicio de Neurología y Neurofisiología Instituto de Biomedicina de Sevilla Hospital Universitario Virgen del Rocío CSIC Universidad de Sevilla Seville Spain

Unit for Hereditary Dementias Theme Aging Karolinska University Hospital Solna Stockholm Sweden

Unitat de Genètica Molecular Institut de Biomedicina de València CSIC Valencia Spain

Unitat Trastorns Cognitius Hospital Universitari Santa Maria de Lleida Lleida Spain

Universidad Autónoma de Madrid Madrid Spain

Université Paris Saclay CEA Centre National de Recherche en Génomique Humaine Evry France

VA San Diego Healthcare System San Diego CA USA

Zurich Center for Integrative Human Physiology University of Zurich Zurich Switzerland

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