Transferability of European-derived Alzheimer's disease polygenic risk scores across multiancestry populations.
| Title: | Transferability of European-derived Alzheimer's disease polygenic risk scores across multiancestry populations. |
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| Authors: | Nicolas A; 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. dr.aude.nicolas.deydier@gmail.com.; Institut du Cerveau - Paris Brain Institute - ICM, Sorbonne Université, CNRS, APHP Hôpital de La Pitié Salpêtrière, Inserm, Paris, France. dr.aude.nicolas.deydier@gmail.com.; Sherva R; Behavioral Sciences Division, National Center for PTSD, VA Boston Healthcare System, Boston, MA, USA.; Department of Medicine (Biomedical Genetics), Boston University, Boston, MA, USA.; Grenier-Boley B; 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.; Kim Y; BK FOUR Department of Integrative Biological Sciences, Chosun University, Gwangju, Republic of Korea.; Kikuchi M; Graduate School of Frontier Science, University of Tokyo, Tokyo, Japan.; Timsina J; Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.; NeuroGenomics and Informatics Center, Washington University School of Medicine, St. Louis, MO, USA.; de Rojas I; ACE Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, Spain.; CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain.; Dalmasso MC; Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital Cologne, Division of Neurogenetics and Molecular Psychiatry, University of Cologne, Cologne, Germany.; Studies in Neuroscience and Complex Systems Unit (ENyS) CONICET-HEC-UNAJ, Santiago, Chile.; Zhou X; Division of Life Science, State Key Laboratory of Molecular Neuroscience, Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Kowloon, China.; Hong Kong Center for Neurodegenerative Diseases, Hong Kong, China.; Guangdong Provincial Key Laboratory of Brain Science, Disease and Drug Development, HKUST Shenzhen Research InstituteShenzhen-Hong Kong Institute of Brain Science, Shenzhen, China.; Le Guen Y; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.; Institut du Cerveau, Paris Brain Institute - ICM, Paris, France.; Arboleda-Bustos CE; Neuroscience and Cell Death Research Groups, Medical School and Genetic Institute, Universidad Nacional de Colombia, Bogota, Colombia.; Camargos Bicalho MA; Department of Clinical Medicine, Federal University of Minas Gerais (UFMG) Belo Horizonte, Minas Geraes, Brazil.; National Institute of Science and Technology (INCT) Neurotec R, Federal University of Minas Geraes Belo Horizonte, Minas Geraes, Brazil.; Geriatrics Service of the University Hospital, Federal University of Minas Gerais Belo Horizonte, Minas Geraes, Brazil.; Guerchet M; 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.; van der Lee S; Department of Neurology, Alzheimer Center Amsterdam, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands.; Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije University, Amsterdam, the Netherlands.; Goss M; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, San Antonio, TX, USA.; Castillo A; Division of Psychological Medicine and Clinical Neuroscience, School of Medicine, Cardiff University, Cardiff, UK.; Bellenguez C; 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.; Küçükali F; Complex Genetics of Alzheimer's Disease Group, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium.; Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.; Satizabal CL; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, San Antonio, TX, USA.; Boston University and the NHLBI's Framingham Heart Study, Boston, MA, USA.; Department of Neurology, Boston University School of Medicine, Boston, MA, USA.; Fongang B; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, San Antonio, TX, USA.; Department of Biochemistry and Structural Biology, University of Texas Health Science Center, San Antonio, TX, USA.; Department of Population Health Sciences, University of Texas Health Science Center, San Antonio, TX, USA.; Yang Q; Boston University and the NHLBI's Framingham Heart Study, Boston, MA, USA.; Department of Neurology, Boston University School of Medicine, Boston, MA, USA.; Peters O; German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany.; 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.; Schneider A; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.; Department for Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Bonn, Germany.; Dichgans M; Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, Munich, Germany.; German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.; Rujescu D; Department of Psychiatry and Comprehensive Center of Neuroscience and Mental Health, Medical University of Vienna, Vienna, Austria.; Scherbaum N; Department of Psychiatry and Psychotherapy, LVR-University Hospital Essen, Medical Faculty of the University of Duisburg-Essen, Essen, Germany.; Deckert J; Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital of Würzburg, Würzburg, Germany.; Riedel-Heller S; Institute of Social Medicine, Occupational Health and Public Health, University of Leipzig, Leipzig, Germany.; Hausner L; Department of Geriatric Psychiatry, Central Institute for Mental Health Mannheim, Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.; Molina-Porcel L; Neurological Tissue Bank - Biobanc, Hospital Clinic, FRCB, IDIBAPS, Barcelona, Spain.; Neurology Department, Alzheimer's Disease and Other Cognitive Disorders Unit, Hospital Clinic, Barcelona, Spain.; Düzel E; German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany.; Institute of Cognitive Neurology and Dementia Research (IKND), Otto-von-Guericke University, Magdeburg, Germany.; Grimmer T; Department of Psychiatry and Psychotherapy, Center for Cognitive Disorders, Technical University of Munich, School of Medicine, Munich, Germany.; Wiltfang J; Department of Psychiatry and Psychotherapy, University Medical Center Goettingen, Goettingen, Germany.; German Center for Neurodegenerative Diseases (DZNE), Goettingen, Germany.; Medical Science Department, iBiMED, Aveiro, Portugal.; Heilmann-Heimbach S; Institute of Human Genetics, University of Bonn, School of Medicine and University Hospital Bonn, Bonn, Germany.; Moebus S; Institute for Urban Public Health, University Hospital Essen, University Duisburg-Essen, Essen, Germany.; Tegos T; First Department of Neurology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece.; Scarmeas N; First Department of Neurology, Aiginition Hospital, National and Kapodistrian University of Athens Medical School, Athens, Greece.; Depatment of Neurology, Columbia University, New York, NY, USA.; Dols-Icardo O; CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain.; Genetics of Neurodegenerative Diseases Unit IIB Sant Pau, Barcelona, Spain.; Moreno F; CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain.; Department of Neurology, Hospital Universitario Donostia, San Sebastian, Spain.; Neurosciences Area, Instituto Biogipuzkoa, San Sebastian, Spain.; Pérez-Tur J; CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain.; Unitat de Genètica Molecular, Institut de Biomedicina de València-CSIC, Valencia, Spain.; Bullido MJ; CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain.; Centro de Biología Molecular Severo Ochoa (UAM-CSIC), Madrid, Spain.; Instituto de Investigacion Sanitaria 'Hospital la Paz' (IdIPaz), Madrid, Spain.; Universidad Autónoma de Madrid, Madrid, Spain.; Pastor P; Department of Neurology, Unit of Neurodegenerative Diseases, University Hospital Germans Trias i Pujol, Badalona, Spain.; The Germans Trias i Pujol Research Institute (IGTP), Badalona, Spain.; Sánchez-Valle R; 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.; Álvarez V; Laboratorio de Genética, Hospital Universitario Central de Asturias, Oviedo, Spain.; Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain.; Cao H; Division of Life Science, State Key Laboratory of Molecular Neuroscience, Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Kowloon, China.; Ip NY; Division of Life Science, State Key Laboratory of Molecular Neuroscience, Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Kowloon, China.; Hong Kong Center for Neurodegenerative Diseases, Hong Kong, China.; Guangdong Provincial Key Laboratory of Brain Science, Disease and Drug Development, HKUST Shenzhen Research InstituteShenzhen-Hong Kong Institute of Brain Science, Shenzhen, China.; Fu AKY; Division of Life Science, State Key Laboratory of Molecular Neuroscience, Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Kowloon, China.; Hong Kong Center for Neurodegenerative Diseases, Hong Kong, China.; Guangdong Provincial Key Laboratory of Brain Science, Disease and Drug Development, HKUST Shenzhen Research InstituteShenzhen-Hong Kong Institute of Brain Science, Shenzhen, China.; Ip FCF; Hong Kong Center for Neurodegenerative Diseases, Hong Kong, China.; Guangdong Provincial Key Laboratory of Brain Science, Disease and Drug Development, HKUST Shenzhen Research InstituteShenzhen-Hong Kong Institute of Brain Science, Shenzhen, China.; Olivar N; Center of Neuropsychiatry and Behavior Neurology, School of Medicine, University of Buenos Aires, Buenos Aires, Argentina.; Muchnik C; Center of Neuropsychiatry and Behavior Neurology, School of Medicine, University of Buenos Aires, Buenos Aires, Argentina.; Cuesta C; Hospital Interzonal General de Agudos-Eva Perón, Buenos Aires, Argentina.; Campanelli L; Laboratory of Brain Aging and Neurodegeneration. Fundacion Instituto Leloir-IIBBA, Buenos Aires, Argentina.; Solis P; Studies in Neuroscience and Complex Systems Unit-CONICET-HEC-UNAJ, Buenos Aires, Argentina.; Politis DG; Hospital Interzonal General de Agudos-Eva Perón, Buenos Aires, Argentina.; Kochen S; Studies in Neuroscience and Complex Systems Unit-CONICET-HEC-UNAJ, Buenos Aires, Argentina.; Brusco LI; Center of Neuropsychiatry and Behavior Neurology, School of Medicine, University of Buenos Aires, Buenos Aires, Argentina.; Boada M; ACE Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, Spain.; CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain.; García-González P; ACE Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, Spain.; Puerta R; ACE Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, Spain.; Mir P; CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain.; Unidad de Trastornos del Movimiento, Servicio de Neurología y Neurofisiología Instituto de Biomedicina de Sevilla (IBiS)Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain.; Real LM; CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain.; Instituto de Biomedicina de Sevilla, IBiS/Hospital Universitario Virgen de Valme, Sevilla, Spain.; Depatamento de Bioquímica Médica, Biología Molecular e Inmunología, Facultad de Medicina, Universidad de Sevilla, Sevilla, Spain.; Piñol-Ripoll G; Unitat Trastorns Cognitius, Hospital Universitari Santa Maria de Lleida, Lleida, Spain.; Institut de Recerca Biomedica de Lleida (IRBLLeida), Lleida, Spain.; García-Alberca JM; CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain.; Alzheimer Research Center and Memory Clinic, Andalusian Institute for Neuroscience, Málaga, Spain.; Royo JL; Depatamento de Especialidades Quirúrgicas, Bioquímica e Inmunología, Facultad de Medicina, Universidad de Málaga, Málaga, Spain.; Rodriguez-Rodriguez E; CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain.; Neurology Service, Marqués de Valdecilla University Hospital (University of Cantabria and IDIVAL), Santander, Spain.; Soininen H; Institute of Clinical Medicine-Neurology, University of Eastern Finland, Kuopio, Finland.; Heikkinen S; Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.; de Mendonça A; Faculty of Medicine, University of Lisbon, Lisbon, Portugal.; Mehrabian S; Clinic of Neurology, UH Alexandrovska, Medical University, Sofia, Bulgaria.; Traykov L; Department of Neurology, UH Alexandrovska, Medical University, Sofia, Bulgaria.; Hort J; Department of Neurology, Memory Clinic, Charles University, Second Faculty of Medicine and Motol University Hospital, Brno, Czech Republic.; International Clinical Research Center, St. Anne's University Hospital Brno, Brno, Czech Republic.; Vyhnalek M; Department of Neurology, Memory Clinic, Charles University, Second Faculty of Medicine and Motol University Hospital, Brno, Czech Republic.; International Clinical Research Center, St. Anne's University Hospital Brno, Brno, Czech Republic.; Rasmussen KL; Department of Clinical Biochemistry, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.; Thomassen JQ; Department of Clinical Biochemistry, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.; Pijnenburg YAL; Department of Neurology, Alzheimer Center Amsterdam, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands.; Holstege H; Department of Neurology, Alzheimer Center Amsterdam, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands.; Department of Clinical Genetics, VU University Medical Centre, Amsterdam, the Netherlands.; van Swieten JC; Alzheimer Center, Department of Neurology, Erasmus MR, Rotterdam, the Netherlands.; Seelaar H; Alzheimer Center, Department of Neurology, Erasmus MR, Rotterdam, the Netherlands.; Claassen JAHR; Department of Geriatrics, Radboud University Medical Center, Research Institute for Medical Innovation, Rotterdam, the Netherlands.; Department of Cardiovascular Sciences, University of Leicester, Leicester, UK.; Jansen WJ; Department of Psychiatry and Neuropsychology, Maastricht University, Alzheimer Center Limburg, Maastricht, the Netherlands.; Ramakers I; Department of Psychiatry and Neuropsychology, Maastricht University, Alzheimer Center Limburg, Maastricht, the Netherlands.; Verhey F; Department of Psychiatry and Neuropsychology, Maastricht University, Alzheimer Center Limburg, Maastricht, the Netherlands.; van der Lugt A; Department of Radiology, ErasmusMC, Rotterdam, the Netherlands.; Scheltens P; Department of Neurology, Alzheimer Center Amsterdam, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands.; Ortega-Rojas J; Neuroscience and Cell Death Research Groups, Medical School and Genetic Institute, Universidad Nacional de Colombia, Bogota, Colombia.; Concha Mera AG; Neuroscience and Cell Death Research Groups, Medical School and Genetic Institute, Universidad Nacional de Colombia, Bogota, Colombia.; Mahecha MF; Neuroscience and Cell Death Research Groups, Medical School and Genetic Institute, Universidad Nacional de Colombia, Bogota, Colombia.; Pardo R; Neuroscience and Cell Death Research Groups, Medical School and Genetic Institute, Universidad Nacional de Colombia, Bogota, Colombia.; Arboleda G; Neuroscience and Cell Death Research Groups, Medical School and Genetic Institute, Universidad Nacional de Colombia, Bogota, Colombia.; Bahrami S; Division of Mental Health and Addiction, NORMENT Centre, Oslo University Hospital, Oslo, Norway.; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.; Fominykh V; Division of Mental Health and Addiction, NORMENT Centre, Oslo University Hospital, Oslo, Norway.; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.; Selbæk G; Norwegian Centre for Ageing and Health, Vestfold Hospital Trust, Tønsberg, Norway.; Faculty of Medicine, University of Oslo, Oslo, Norway.; Department of Geriatric Medicine, Oslo University Hospital, Oslo, Norway.; Graff C; Unit for Hereditary Dementias, Theme Aging, Karolinska University Hospital-Solna, Stockholm, Sweden.; Papenberg G; Department of Neurobiology, Care Sciences and Society, Aging Research Center, Karolinska Institutet and Stockholm University, Stockholm, Sweden.; Giedraitis V; Department of Public Health and Carins Sciences/Geriatrics, Uppsala University, Uppsala, Sweden.; Boland A; Université Paris-Saclay, CEA, Centre National de Recherche en Génomique Humaine (CNRGH), Evry, France.; Deleuze JF; Université Paris-Saclay, CEA, Centre National de Recherche en Génomique Humaine (CNRGH), Evry, France.; de Marco LA; National Institute of Science and Technology (INCT) Neurotec R, Federal University of Minas Geraes Belo Horizonte, Minas Geraes, Brazil.; Department of Surgery, Federal University of Minas Gerais (UFMG) Belo Horizonte, Minas Geraes, Brazil.; de Moraes EN; Department of Clinical Medicine, Federal University of Minas Gerais (UFMG) Belo Horizonte, Minas Geraes, Brazil.; Geriatrics Service of the University Hospital, Federal University of Minas Gerais Belo Horizonte, Minas Geraes, Brazil.; de Mattos Viana B; National Institute of Science and Technology (INCT) Neurotec R, Federal University of Minas Geraes Belo Horizonte, Minas Geraes, Brazil.; Department of Psychiatry, Federal University of Minas Gerais (UFMG) Belo Horizonte, Minas Geraes, Brazil.; Psychiatry Service of the University Hospital, Federal University of Minas Gerais, Belo Horizonte, Minas Geraes, Brazil.; Túlio Gualberto Cintra M; Department of Clinical Medicine, Federal University of Minas Gerais (UFMG) Belo Horizonte, Minas Geraes, Brazil.; Geriatrics Service of the University Hospital, Federal University of Minas Gerais Belo Horizonte, Minas Geraes, Brazil.; Juarez-Cedillo T; Unidad de Investigación Epidemiológica y en Servicios de Salud, Área Envejecimiento, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico.; Griswold AJ; The John P. Hussman Institute for Human Genomics, University of Miami, Miami, FL, USA.; Forund T; Department of Medical and Molecular Genetics, Indiana University, Indianapolis, IN, USA.; Haines J; Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, USA.; Farrer L; Department of Medicine (Biomedical Genetics), Boston University, Boston, MA, USA.; Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.; Department of Epidemiology, Boston University, Boston, MA, USA.; Department of Neurology, Boston University, Boston, MA, USA.; Department of Ophthalmology, Boston University, Boston, MA, USA.; DeStefano A; Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.; Wijsman E; Department of Medicine (Medical Genetics), University of Washington, Seattle, WA, USA.; Department of Biostatistics, University of Washington, Seattle, WA, USA.; Department of Genome Sciences, University of Washington, Seattle, WA, USA.; Mayeux R; Department of Neurology, Taub Institute on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, USA.; Gertrude H. Sergievsky Center, Columbia University, New York, NY, USA.; Pericak-Vance M; The John P. Hussman Institute for Human Genomics, University of Miami, Miami, FL, USA.; Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami, Miami, FL, USA.; Kunkle B; The John P. Hussman Institute for Human Genomics, University of Miami, Miami, FL, USA.; Goate A; Department of Neuroscience, Mount Sinai School of Medicine, New York, NY, USA.; Schellenberg GD; Department of Pathology and Laboratory Medicine, Penn Neurodegeneration Genomics Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.; Vardarajan B; Department of Neurology, Taub Institute on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, USA.; Gertrude H. Sergievsky Center, Columbia University, New York, NY, USA.; Department of Neurology, Columbia University, New York, NY, USA.; Wang LS; Department of Pathology and Laboratory Medicine, Penn Neurodegeneration Genomics Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.; Leung YY; Department of Pathology and Laboratory Medicine, Penn Neurodegeneration Genomics Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.; Dalgard CL; Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.; Center for Military Precision Health, The American Genome Center, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.; Nicolas G; Department of Genetics and CNR-MAJ, Université Rouen Normandie, Normandie Université, Inserm U1245 and CHU Rouen, Rouen, France.; Wallon D; Department of Genetics and CNR-MAJ, Université Rouen Normandie, Normandie Université, Inserm U1245 and CHU Rouen, Rouen, France.; Dufouil C; Bordeaux Population Health Research Center, Inserm, UMR 1219, Université Bordeaux, ISPED, CIC 1401-EC, Université Bordeaux, Bordeaux, France.; CHU de Bordeaux, Pole Santé Publique, Bordeaux, France.; Pasquier F; CHU Clinical and Research Memory Research Centre (CMRR) of Distalz Lille France, Université Lille Inserm 1171, Paris, France.; Hanon O; Hôpital Broca, Université de Paris, EA 4468, APHP, Paris, France.; Debette S; Bordeaux Population Health Research Center, University Bordeaux, Inserm, Bordeaux, France.; Department of Neurology, Bordeaux University Hospital, Bordeaux, France.; Grünblatt E; Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, University of Zurich, Zurich, Switzerland.; Neuroscience Center Zurich, University of Zurich and ETH Zurich, Zurich, Switzerland.; Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland.; Popp J; Department of Psychiatry, Old Age Psychiatry, Lausanne University Hospital, Lausanne, Switzerland.; Department of Geriatric Psychiatry, University Hospital of Psychiatry Zürich, Zurich, Switzerland.; Institute for Regenerative Medicine, University of Zürich, Zurich, Switzerland.; Angel B; Public Health Nutrition Unit, Institute of Nutrition and Food Technology, University of Chile, Santiago de Chile, Chile.; Interuniversity Center for Healthy Aging RED21993, Santiago de Chile, Chile.; Gloger S; Biomedica Research Group, Centro de Estudios Clínicos, Santiago, Chile.; Departamento de Psiquiatría y Salud Mental, Campus Oriente, Facultad de MedicinaUniversidad de Chile, Santiago, Chile.; Chacon MV; Biomedica Research Group, Centro de Estudios Clínicos, Santiago, Chile.; Aranguiz R; Biomedica Research Group, Centro de Estudios Clínicos, Santiago, Chile.; Instituto Nacional de Geriatría, Santiago, Chile.; Department of Neurology and Psychiatry, Clínica Alemana, Santiago, Chile.; Orellana P; Geroscience Center for Brain Health and Metabolism, Santiago, Chile.; Latin American Institute for Brain Health (BrainLat), Universidad Adolfo Ibanez, Santiago, Chile.; Slachevsky A; Geroscience Center for Brain Health and Metabolism, Santiago, Chile.; Memory and Neuropsychiatric Center (CMYN) Neurology Department, Hospital del Salvador y Facultad de Medicina, Universidad de Chile, Santiago, Chile.; Gonzalez-Billault C; Public Health Nutrition Unit, Institute of Nutrition and Food Technology, University of Chile, Santiago de Chile, Chile.; Geroscience Center for Brain Health and Metabolism, Santiago, Chile.; Albala C; Public Health Nutrition Unit, Institute of Nutrition and Food Technology, University of Chile, Santiago de Chile, Chile.; Interuniversity Center for Healthy Aging RED21993, Santiago de Chile, Chile.; Fuentes P; Geriatrics Section Clinical Hospital University of Chile, Santiago de Chile, Chile.; Neurology Service Hospital del Salvador, Santiago, Chile.; Sachdev P; Centre for Healthy Brain Ageing School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia.; Mather KA; Centre for Healthy Brain Ageing School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia.; Hauger RL; Center of Excellence for Stress and Mental Health (CESAMH), VA San Diego Healthcare System, San Diego, CA, USA.; Center for Behavior Genetics of Aging, University of California San Diego, La Jolla, CA, USA.; Merritt V; VA San Diego Healthcare System, San Diego, CA, USA.; Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.; Center of Excellence for Stress and Mental Health, VA San Diego Healthcare System, San Diego, CA, USA.; Panizzon M; Center for Behavior Genetics of Aging, University of California San Diego, La Jolla, CA, USA.; Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.; Center of Excellence for Stress and Mental Health, VA San Diego Healthcare System, San Diego, CA, USA.; Zhang R; Behavioral Sciences Division, National Center for PTSD, VA Boston Healthcare System, Boston, MA, USA.; Gaziano JM; Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston, MA, USA.; Division of Aging, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.; Ghidoni R; Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.; Galimberti D; Neurodegenerative Diseases Unit, Fondazione IRCCS Ca' Granda, Ospedale Policlinico, Milan, Italy.; Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy.; Arosio B; Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.; Mecocci P; Institute of Gerontology and Geriatrics, Department of Medicine and Surgery, University of Perugia, Perugia, Italy.; Department of Neurobiology, Care Sciences and Society, Division of Clinical Geriatrics, Karolinska Institutet, Stockholm, Sweden.; Solfrizzi V; Interdisciplinary Department of Medicine, Geriatric Medicine and Memory Unit, University of Bari A. Moro, Bari, Italy.; Parnetti L; Centre for Memory Disturbances, Laboratory of Clinical Neurochemistry, Section of Neurology, University of Perugia, Perugia, Italy.; Squassina A; Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy.; Tremolizzo L; Neurology, IRCCS San Gerardo dei Tintori, Monza and University of Milano-Bicocca, Milano, Italy.; Borroni B; Deaprtment of Clinical and Experimental Sciences, University of Brescia Italy, Brescia, Italy.; Department of Continuity of Care and Frailty, ASST Spedali Civili Brescia, Brescia, Italy.; Nacmias B; Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy.; IRCCS Fondazione Don Carlo Gnocchi, Florence, Italy.; Caffarra P; Past Director Dementia Unit University of Parma, Parma, Italy.; Seripa D; Department of Hematology and Stem Cell Transplant, Vito Fazzi Hospital, Lecce, Italy.; Rainero I; Department of Neuroscience Rita Levi Montalcini, University of Torino, Turin, Italy.; Daniele A; Department of Neuroscience, Università Cattolica del Sacro Cuore, Rome, Italy.; Neurology Unit, IRCCS Fondazione Policlinico Universitario A. Gemelli, Rome, Italy.; Piras F; Laboratory of Neuropsychiatry, IRCCS Santa Lucia Foundation, Rome, Italy.; Leonard HL; Center for Alzheimer's and Related Dementias, NIH, Bethesda, MD, USA.; DataTecnica LLC, Washington, DC, USA.; Yokoyama JS; DataTecnica LLC, Washington, DC, USA.; Department of Neurology, Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, CA, USA.; Pharmaceutical Sciences and Pharmacogenomics Graduate Program, University of California, San Francisco, CA, USA.; Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA.; Nalls MA; Center for Alzheimer's and Related Dementias, NIH, Bethesda, MD, USA.; DataTecnica LLC, Washington, DC, USA.; Laboratory of Neurogenetics, NIH, Bethesda, MD, USA.; Miyashita A; Niigata University, Brain Research Institute, Niigata, Japan.; Hara N; Niigata University, Brain Research Institute, Niigata, Japan.; Ozaki K; Research Center, National Center for Geriatrics and Gerontology, Obu, Japan.; Niida S; Research Center, National Center for Geriatrics and Gerontology, Obu, Japan.; Williams J; Division of Psychological Medicine and Clinical Neuroscience, School of Medicine, Cardiff University, Cardiff, UK.; UK Dementia Research Institute, Cardiff University, Cardiff, UK.; Masullo C; Institute of Neurology, Catholic University of the Sacred Heart, Rome, Italy.; Amouyel P; 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.; Preux PM; 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.; Mbelesso P; 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.; Department of Neurology, Amitié Hospital, Bangui, Central African Republic.; Bandzouzi B; Department of Neurology, Brazzaville University Hospital, Brazzaville, Republic of Congo.; Saykin A; Department of Medical and Molecular Genetics, Indiana University, Indianapolis, IN, USA.; Department of Radiology, Indiana University, Indianapolis, IN, USA.; Jessen F; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.; Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.; Cluster of Excellence Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.; Kehoe PG; Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.; Van Duijn C; Department of Epidemiology, ErasmusMC, Rotterdam, the Netherlands.; Nuffield Department of Population Health, Oxford University, Oxford, UK.; Ben Salem N; High Institute of Biotechnology, University of Monastir, Monastir, Tunisia.; Frikke-Schmidt R; Department of Clinical Biochemistry, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.; Cherni L; High Institute of Biotechnology, University of Monastir, Monastir, Tunisia.; Laboratory of Genetics, Immunology and Human Pathology, Faculty of Science of Tunis, University of Tunis El Manar, Tunis, Tunisia.; Greicius MD; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.; Tsolaki M; First Department of Neurology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece.; Laboratory of Genetics, Immunology and Human Pathology, Faculty of Science of Tunis, University of Tunis El Manar, Tunis, Tunisia.; Sánchez-Juan P; CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain.; Alzheimer's Centre Reina Sofia-CIEN Foundation-ISCIII, Madrid, Spain.; Romano Silva MA; National Institute of Science and Technology (INCT) Neurotec R, Federal University of Minas Geraes Belo Horizonte, Minas Geraes, Brazil.; Department of Psychiatry, Federal University of Minas Gerais (UFMG) Belo Horizonte, Minas Geraes, Brazil.; Porter T; Centre for Precision Health, Edith Cowan University, Perth, Western Australia, Australia.; Collaborative Genomics and Translation Group, School of Medical and Health Sciences, Edith Cowan University, Perth, Western Australia, Australia.; Curtin Health Innovation Research Institute, Curtin University, Perth, Western Australia, Australia.; Laws SM; Centre for Precision Health, Edith Cowan University, Perth, Western Australia, Australia.; Collaborative Genomics and Translation Group, School of Medical and Health Sciences, Edith Cowan University, Perth, Western Australia, Australia.; Curtin Health Innovation Research Institute, Curtin University, Perth, Western Australia, Australia.; Sleegers K; Complex Genetics of Alzheimer's Disease Group, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium.; Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.; Ingelsson M; Department of Public Health and Caring Sciences/Geriatrics, Uppsala University, Uppsala, Sweden.; Krembil Brain Institute, University Health Network, Toronto, Ontario, Canada.; Departments of Medicine and Laboratory Medicine and Pathobiology, Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada.; Dartigues JF; Bordeaux Population Health Research Center, INSERM, Bordeaux UMR 1219, Bordeaux, France.; Seshadri S; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, San Antonio, TX, USA.; Boston University and the NHLBI's Framingham Heart Study, Boston, MA, USA.; Department of Neurology, Boston University School of Medicine, Boston, MA, USA.; Rossi G; Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.; Morelli L; Laboratory of Brain Aging and Neurodegeneration. Fundacion Instituto Leloir-IIBBA, Buenos Aires, Argentina.; Hiltunen M; Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.; Sims R; Division of Psychological Medicine and Clinical Neuroscience, School of Medicine, Cardiff University, Cardiff, UK.; van der Flier W; Department of Neurology, Alzheimer Center Amsterdam, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands.; Andreassen OA; Division of Mental Health and Addiction, NORMENT Centre, Oslo University Hospital, Oslo, Norway.; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.; Arboleda H; Neuroscience and Cell Death Research Groups, Medical School and Genetic Institute, Universidad Nacional de Colombia, Bogota, Colombia.; Cruchaga C; Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.; NeuroGenomics and Informatics Center, Washington University School of Medicine, St. Louis, MO, USA.; Escott-Price V; UK Dementia Research Institute, Cardiff University, Cardiff, UK.; Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Cardiff, UK.; Ruiz A; ACE Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, Spain.; CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain.; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, University of Texas Health Sciences Center, San Antonio, TX, USA.; Lee KH; BK FOUR Department of Integrative Biological Sciences, Chosun University, Gwangju, Republic of Korea.; Department of Biomedical Science, Chosun University, Gwangju, Republic of Korea.; Gwangju Alzheimer's and Related Dementia (GARD) Cohort Research Center, Chosun University, Gwangju, Republic of Korea.; Ikeuchi T; Niigata University, Brain Research Institute, Niigata, Japan.; Ramirez A; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, University of Texas Health Sciences Center, San Antonio, TX, USA.; Division of Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, University of Cologne, Medical Faculty, Cologne, Germany.; German Center for Neurodegenerative Diseases (DZNE Bonn), Bonn, Germany.; Department of Old Age Psychiatry and Cognitive Disorders, University Hospital Bonn, University of Bonn, Bonn, Germany.; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Disease (CECAD), University of Cologne, Cologne, Germany.; Gim J; BK FOUR Department of Integrative Biological Sciences, Chosun University, Gwangju, Republic of Korea.; Department of Biomedical Science, Chosun University, Gwangju, Republic of Korea.; Gwangju Alzheimer's and Related Dementia (GARD) Cohort Research Center, Chosun University, Gwangju, Republic of Korea.; Logue M; Behavioral Sciences Division, National Center for PTSD, VA Boston Healthcare System, Boston, MA, USA.; Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.; Department of Psychiatry, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, USA.; Biomedical Genetics/Department of Medicine, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, USA.; Lambert JC; 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. jean-charles.lambert@pasteur-lille.fr. |
| Corporate Authors: | EADB |
| Source: | Nature genetics [Nat Genet] 2025 Jul; Vol. 57 (7), pp. 1598-1610. Date of Electronic Publication: 2025 Jun 18. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Nature Pub. Co Country of Publication: United States NLM ID: 9216904 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1546-1718 (Electronic) Linking ISSN: 10614036 NLM ISO Abbreviation: Nat Genet Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: New York, NY : Nature Pub. Co., c1992- |
| MeSH Terms: | Alzheimer Disease*/genetics ; Alzheimer Disease*/epidemiology ; Alzheimer Disease*/cerebrospinal fluid ; Multifactorial Inheritance*/genetics ; White People*/genetics ; Genetic Predisposition to Disease*; Europe/epidemiology ; Apolipoproteins E/genetics ; Biomarkers/cerebrospinal fluid ; Humans ; Genome-Wide Association Study ; Female ; Risk Factors ; Male ; Polymorphism, Single Nucleotide ; Aged ; Genetic Risk Score |
| Abstract: | 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.; (© 2025. The Author(s).) |
| Competing Interests: | Competing interests: S.v.d.L. is a recipient of funding from ABOARD, which is a public–private partnership financed by ZonMW (no. 73305095007) and Health–Holland, Topsector Life Sciences & Health (PPP-allowance; no. LSHM20106). C.C. has received research support from GSK and EISAI. The study’s funders had no role in the collection, analysis or interpretation of data; in the writing of the report or in the decision to submit the paper for publication. C.C. is an advisory board member for Vivid Genomics and Circular Genomics and owns stock. L.M.-P. received personal fees from Biogen for consulting activities unrelated to the submitted work. T.G. received consulting fees from AbbVie, Alector, Anavex, Biogen, Cogthera, Eli Lilly, Functional Neuromodulation, Grifols, Iqvia, Janssen, Noselab, Novo Nordisk, NuiCare, Orphanzyme, Roche Diagnostics, Roche Pharma, UCB and Vivoryon; lecture fees from Biogen, Eisai, Grifols, Medical Tribune, Novo Nordisk, Roche Pharma, Schwabe and Synlab; and has received grants to his institution from Biogen, Eisai and Roche Diagnostics. O.A.A. is a consultant to Cortechs and Precision Health AS, and has received speaker’s honoraria from Lundbeck, Sunovion, Otsuka and Janssen. The other authors declare no competing interests. |
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| Grant Information: | R01 HL105756 United States HL NHLBI NIH HHS; UG3 AG090675 United States AG NIA NIH HHS; P30 AG059305 United States AG NIA NIH HHS; P30 AG066546 United States AG NIA NIH HHS; I01 BX005749 United States BX BLRD VA; K01 NS126489 United States NS NINDS NIH HHS |
| Contributed Indexing: | Investigator: S Moreno-Grau; N Amin; PA Holmans; L Kleineidam; D Aarsland; P Garcia-Gonzalez; C Abdelnour; E Alarcón-Martín; D Alcolea; M Alegret; I Alvarez; NJ Armstrong; T Anthoula; I Appollonio; M Arcaro; S Archetti; A Arias Pastor; L Athanasiu; H Bailly; N Banaj; M Baquero; AB Pastor; S Bellini; C Berr; C Besse; V Bessi; G Binetti; A Bizarro; R Blesa; S Boschi; P Bossù; G Bråthen; C Bresner; H Brodaty; KJ Brookes; D Buiza-Rueda; K Bûrger; V Burholt; M Calero; G Chene; Á Carracedo; R Cecchetti; L Cervera-Carles; C Charbonnier; C Chillotti; S Ciccone; J Clarimon; C Clark; E Conti; A Corma-Gómez; GM Giuffrè; C Custodero; D Daian; E Dardiotis; PP de Deyn; T Del Ser; N Denning; J Diehl-Schmid; M Diez-Fairen; PD Rossi; S Djurovic; E Duron; S Engelborghs; A Espinosa; M Ewers; T Fabrizio; SF Nielsen; L Farotti; C Fenoglio; M Fernández-Fuertes; CB Ferreira; E Ferri; B Fin; P Fischer; T Fladby; K Fließbach; J Fortea; TM Foroud; S Fostinelli; NC Fox; E Franco-Macías; A Frank-García; L Froelich; JM García-Alberca; S Garcia-Madrona; G Garcia-Ribas; I Giegling; G Giorgio; O Goldhardt; A González-Pérez; G Grande; E Green; T Guetta-Baranes; A Haapasalo; G Hadjigeorgiou; H Hampel; J Hardy; AM Hartmann; J Harwood; S Helisalmi; MT Heneka; I Hernández; MJ Herrmann; P Hoffmann; C Holmes; R Huerto Vilas; M Hulsman; GJ Biessels; C Johansson; L Kilander; AK Ståhlbom; M Kivipelto; A Koivisto; J Kornhuber; MH Kosmidis; C Lage; EJ Laukka; A Lauria; J Lehtisalo; O Lerch; A Lleó; A López-de Munain; S Love; M Löwemark; L Luckcuck; J Macías; CA MacLeod; W Maier; F Mangialasche; M Spallazzi; M Marquié; R Marshall; AM Montes; C Martínez Rodríguez; S Mead; M Medina; A Meggy; S Mendoza; M Menéndez-González; M Mol; L Montrreal; K Morgan; MM Möthen; T Ngandu; BG Nordestgaard; R Olaso; A Orellana; M Orsini; G Ortega; A Padovani; A Pérez-Cordón; P Pericard; JA Pineda; C Pisanu; T Polak; D Posthuma; J Priller; O Quenez; I Quintela; A Rábano; MJT Reinders; P Riederer; N Roberto; A Rongve; IR Allende; M Rosende-Roca; JL Royo; E Rubino; ME Sáez; P Sakka; I Saltvedt; Á Sanabria; M Bernal Sánchez-Arjona; F Sanchez-Garcia; P Sánchez-Juan; SB Sando; M Scamosci; E Scarpini; M Scherer; M Schmid; JM Schott; AA Shadrin; O Skrobot; A Solomon; S Sorbi; O Sotolongo-Grau; A Spottke; E Stordal; JP Tartan; L Tárraga; N Tesí; A Thalamuthu; T Thomas; A Tybjærg-Hansen; A Uitterlinden; A Ullgren; I Ulstein; S Valero; C Van Broeckhoven; J Van Dongen; R Vandenberghe; JS Vidal; J Vogelgsang; M Wagner; L Weinhold; G Windle; B Woods; M Yannakoulia; M Zulaica |
| Substance Nomenclature: | 0 (Apolipoproteins E); 0 (Biomarkers) |
| Entry Date(s): | Date Created: 20250618 Date Completed: 20250722 Latest Revision: 20260501 |
| Update Code: | 20260501 |
| PubMed Central ID: | PMC12283339 |
| DOI: | 10.1038/s41588-025-02227-w |
| PMID: | 40533518 |
| Database: | MEDLINE |
Journal Article