ArticleNature communications2025
Machine learning in Alzheimer's disease genetics.
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Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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9citing papers in PubMed
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Who cites it
9 citing papers in PubMed.
- Golgi dysfunction in Alzheimer disease: from human multiomic signatures to therapeutic targets.Experimental & molecular medicine · 2026Review
- Sex-dependent interferon signaling contributes to female-biased vulnerability in Alzheimer's disease.Journal of neuroinflammation · 2026Article
- Comparison and validation of multiple machine learning algorithms for predicting MDRO infection in catheter-related bloodstream patients: a multicenter cohort study.Microbiology spectrum · 2026Article
- Immunometabolism Reframes Alzheimer's Disease: From Systemic Dysmetabolism to Glial Rewiring.Cellular and molecular neurobiology · 2026Review
- Machine learning for Alzheimer's disease progression under extreme class imbalance.Frontiers in neuroscience · 2026Article
- Alzheimer's disease: genetic background in the era of next-generation sequencing technologies.Brain communications · 2026Review
- Identification of hidden subtypes in occupational health examinations and their biomedical characteristics using graph-enhanced deep representation learning.Frontiers in public health · 2026Article
- Leveraging a machine learning model to predict hospital readmission risk: integrating clinical and social determinants of health data.Frontiers in public health · 2026Article
- Unsupervised machine learning integrates genomic variants and EMR to unravel mechanisms of brain hemorrhage and epilepsy as early indicators of Alzheimer's in down syndrome.Alzheimer's research & therapy · 2025Article
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Authors and funding
113 authors.
Matthew Bracher-Smith *School of Medicine, Cardiff University, Cardiff, UK.ORCID http://orcid.org/0000-0002-0531-6309
Federico Melograna *BIO3 - Systems Medicine, Department of Human Genetics, KU Leuven, Leuven, Belgium.
Brittany Ulm *Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
Céline BellenguezUniv. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, LabEx DISTALZ - U1167-RID-AGE Facteurs de risque et déterminants moléculaires des maladies liées au vieillissement, Lille, France.ORCID http://orcid.org/0000-0002-1240-7874
Benjamin Grenier-BoleyUniv. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, LabEx DISTALZ - U1167-RID-AGE Facteurs de risque et déterminants moléculaires des maladies liées au vieillissement, Lille, France.
Diane DurouxBIO3 - Systems Genetics, GIGA-R Molecular and Computational Biology, University of Liege, Liege, Belgium.
Alejo J NevadoCentre for Artificial Intelligence in Precision Medicine, University of Oxford, Oxford, United Kingdom.
Peter HolmansCentre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neuroscience, School of Medicine, Cardiff University, Cardiff, UK.ORCID http://orcid.org/0000-0003-0870-9412
Betty M TijmsAlzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.ORCID http://orcid.org/0000-0002-2612-1797
Marc HulsmanAlzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.ORCID http://orcid.org/0000-0002-9889-3606
Itziar de RojasResearch Center and Memory Clinic, ACE Alzheimer Center Barcelona. Universitat Internacional de Catalunya, Catalunya, Spain.ORCID http://orcid.org/0000-0002-2148-381X
Rafael Campos-MartinDivision of Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.ORCID http://orcid.org/0000-0002-1395-8571
Sven van der LeeAlzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.ORCID http://orcid.org/0000-0003-1606-8643
Atahualpa CastilloCentre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neuroscience, School of Medicine, Cardiff University, Cardiff, UK.
Fahri KüçükaliComplex Genetics of Alzheimer's Disease Group, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium.ORCID http://orcid.org/0000-0002-3835-9639
Oliver PetersGerman Center for Neurodegenerative Diseases (DZNE), Berlin, Germany.ORCID http://orcid.org/0000-0003-0568-2998
Anja SchneiderGerman Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.ORCID http://orcid.org/0000-0001-9540-8700
Martin DichgansInstitute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, Munich, Germany.ORCID http://orcid.org/0000-0002-0654-387X
Dan RujescuDepartment of Psychiatry and Psychotherapy, Comprehensive Center for Clinical Neurosciences and Mental Health (C3NMH), Medical University of Vienna, Vienna, Austria.ORCID http://orcid.org/0000-0002-1432-313X
Norbert ScherbaumDepartment of Psychiatry and Psychotherapy, LVR-Klinikum Essen, University of Duisburg-Essen, Germany Medical Faculty, Essen, Germany.ORCID http://orcid.org/0000-0003-1759-6990
Jürgen DeckertDepartment of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital of Würzburg, Würzburg, Germany.
Steffi Riedel-HellerInstitute of Social Medicine, Occupational Health and Public Health, University of Leipzig, 04103, Leipzig, Germany.ORCID http://orcid.org/0000-0003-4321-6090
Lucrezia HausnerDepartment of Geriatric Psychiatry, Central Institute for Mental Health Mannheim, Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.ORCID http://orcid.org/0000-0001-9009-2356
Laura Molina-PorcelAlzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic of Barcelona, Fundació Recerca Clinic Barcelona- Institut d'Investigacions Biomèdiques August Pi i Sunyer (FRCB-IDIBAPS), and University of Barcelona, Barcelona, Spain.ORCID http://orcid.org/0000-0003-4068-8578
Emrah DüzelGerman Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany.
Timo GrimmerCenter for Cognitive Disorders, Department of Psychiatry and Psychotherapy, Technical University of Munich, School of Medicine and Health, Klinikum rechts der Isar, Munich, Germany.
Jens WiltfangDepartment of Psychiatry and Psychotherapy, University Medical Center Goettingen, Goettingen, Germany.ORCID http://orcid.org/0000-0003-1492-5330
Stefanie Heilmann-HeimbachInstitute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany.ORCID http://orcid.org/0000-0003-1057-465X
Susanne MoebusInstitute for Urban Public Health, University Hospital of University Duisburg-Essen, Essen, Germany.ORCID http://orcid.org/0000-0002-0072-5410
Thomas Tegos1st Department of Neurology, Medical school, Aristotle University of Thessaloniki, Thessaloniki, Makedonia, Greece.
Nikolaos ScarmeasTaub Institute for Research in Alzheimer's Disease and the Aging Brain, The Gertrude H. Sergievsky Center, Depatment of Neurology, Columbia University, New York, NY, USA.
Oriol Dols-IcardoSant Pau Memory Unit, Institut de Recerca Sant Pau, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.ORCID http://orcid.org/0000-0003-2656-8748
Fermin MorenoCIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain.ORCID http://orcid.org/0000-0001-5200-3164
Jordi Pérez-TurCIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain.ORCID http://orcid.org/0000-0002-9111-1712
María J BullidoCIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain.ORCID http://orcid.org/0000-0002-6477-1117
Pau PastorFundació Docència i Recerca MútuaTerrassa, Terrassa, Barcelona, Spain.ORCID http://orcid.org/0000-0002-7493-8777
Raquel Sánchez-ValleAlzheimer'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.
Victoria ÁlvarezLaboratorio de Genética. Hospital Universitario Central de Asturias, Oviedo, Spain.ORCID http://orcid.org/0000-0002-1916-2523
Mercè BoadaCIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain.ORCID http://orcid.org/0000-0003-2617-3009
Pablo García-GonzálezResearch Center and Memory clinic. ACE Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, Spain.ORCID http://orcid.org/0000-0003-0125-5403
Raquel PuertaResearch Center and Memory clinic. ACE Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, Spain.ORCID http://orcid.org/0000-0002-1191-5893
Pablo MirCIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain.ORCID http://orcid.org/0000-0003-1656-302X
Luis M RealUnidad Clínica de Enfermedades Infecciosas y Microbiología. Hospital Universitario de Valme, Sevilla, Spain.ORCID http://orcid.org/0000-0003-4932-7429
Gerard Piñol-RipollUnitat Trastorns Cognitius, Hospital Universitari Santa Maria de Lleida, Lleida, Spain.
Jose María García-AlbercaCIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain.ORCID http://orcid.org/0000-0003-2951-6644
Eloy Rodriguez-RodriguezCIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain.ORCID http://orcid.org/0000-0001-7742-677X
Hilkka SoininenInstitute of Clinical Medicine - Neurology, University of Eastern Finland, Kuopio, Finland.ORCID http://orcid.org/0000-0002-2785-9937
Sami HeikkinenInstitute of Biomedicine, University of Eastern Finland, Kuopio, Finland.ORCID http://orcid.org/0000-0002-6083-2402
Alexandre de MendonçaFaculty of Medicine, University of Lisbon, Lisbon, Portugal.
Shima MehrabianClinic of Neurology, UH "Alexandrovska", Medical University - Sofia, Sofia, Bulgaria.
Latchezar TraykovDepartment of Neurology, Medical University - Sofia, Sofia, Bulgaria.
Jakub HortMemory Clinic, Department of Neurology, Charles University, Second Faculty of Medicine and Motol University Hospital, Praha, Czech Republic.ORCID http://orcid.org/0000-0002-1080-3726
Martin VyhnalekMemory Clinic, Department of Neurology, Charles University, 2nd Faculty of Medicine and Motol University Hospital, Praha, Czech Republic.
Nicolai SandauDepartment of Clinical Biochemistry, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
Jesper Qvist ThomassenDepartment of Clinical Biochemistry, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.ORCID http://orcid.org/0000-0003-3484-9531
Yolande A L PijnenburgAlzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.
Henne HolstegeAlzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.ORCID http://orcid.org/0000-0002-7688-3087
John van SwietenDepartment of Neurology, ErasmusMC, Rotterdam, Netherlands.
Inez RamakersMaastricht University, Department of Psychiatry & Neuropsychologie, Alzheimer Center Limburg, Maastricht, the Netherlands.
Frans VerheyMaastricht University, Department of Psychiatry & Neuropsychologie, Alzheimer Center Limburg, Maastricht, the Netherlands.
Philip ScheltensAlzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.ORCID http://orcid.org/0000-0002-1046-6408
Caroline GraffUnit for Hereditary Dementias, Theme Aging, Karolinska University Hospital-Solna, 171 64, Stockholm, Sweden.
Goran PapenbergAging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet and Stockholm University, Stockholm, Sweden.
Vilmantas GiedraitisDept.of Public Health and Carins Sciences / Geriatrics, Uppsala University, Uppsala, Sweden.ORCID http://orcid.org/0000-0003-3423-2021
Julie WilliamsSchool of Medicine, Cardiff University, Cardiff, UK.ORCID http://orcid.org/0000-0002-4069-0259
Philippe AmouyelUniv. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, LabEx DISTALZ - U1167-RID-AGE Facteurs de risque et déterminants moléculaires des maladies liées au vieillissement, Lille, France.ORCID http://orcid.org/0000-0001-9088-234X
Anne BolandUniversité Paris-Saclay, CEA, Centre National de Recherche en Génomique Humaine, 91057, Evry, France.ORCID http://orcid.org/0000-0001-8789-5676
Jean-François DeleuzeUniversité Paris-Saclay, CEA, Centre National de Recherche en Génomique Humaine, 91057, Evry, France.
Gael NicolasUniv Rouen Normandie, Normandie Univ, Inserm U1245 and CHU Rouen, Department of Genetics and CNRMAJ, F-, 76000, Rouen, France.ORCID http://orcid.org/0000-0001-9391-7800
Carole DufouilInserm, Bordeaux Population Health Research Center, UMR 1219, Univ. Bordeaux, ISPED, CIC 1401-EC, Univ Bordeaux, Bordeaux, France.ORCID http://orcid.org/0000-0003-2442-4476
Florence PasquierUniv Lille Inserm 1171, CHU Clinical and Research Memory Research Centre (CMRR) of Distalz Lille France, Lille, France.ORCID http://orcid.org/0000-0001-9880-9788
Olivier HanonUniversité de Paris, EA 4468, APHP, Hôpital Broca, Paris, France.
Stéphanie DebetteUniversity Bordeaux, Inserm, Bordeaux Population Health Research Center, Bordeaux, France.ORCID http://orcid.org/0000-0001-8675-7968
Edna GrünblattDepartment of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, University of Zurich, Zurich, Switzerland.ORCID http://orcid.org/0000-0001-8505-7265
Julius PoppCHUV, Old Age Psychiatry, Department of Psychiatry, Lausanne, Switzerland.
Roberta GhidoniMolecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.ORCID http://orcid.org/0000-0002-7691-1957
Daniela GalimbertiNeurodegenerative Diseases Unit, Fondazione IRCCS Ca' Granda, Ospedale Policlinico, Milan, IT, Italy.ORCID http://orcid.org/0000-0002-9284-5953
Beatrice ArosioDepartment of Clinical Sciences and Community Health, University of Milan, 20122, Milan, Italy.ORCID http://orcid.org/0000-0002-0615-3580
Patrizia MecocciInstitute of Gerontology and Geriatrics, Department of Medicine and Surgery, University of Perugia, Perugia, Italy.ORCID http://orcid.org/0000-0003-0729-5246
Vincenzo SolfrizziInterdisciplinary Department of Medicine, Geriatric Medicine and Memory Unit, University of Bari "A. Moro", Bari, Italy.ORCID http://orcid.org/0000-0002-8524-0315
Lucilla ParnettiCentre for Memory Disturbances, Lab of Clinical Neurochemistry, Section of Neurology, University of Perugia, Perugia, Italy.ORCID http://orcid.org/0000-0001-5722-3967
Alessio SquassinaDepartment of Biomedical Sciences, Section of Neuroscience and Clinical Pharmacology, University of Cagliari, Cagliari, Italy.ORCID http://orcid.org/0000-0001-7415-7607
Lucio TremolizzoNeurology Unit, "San Gerardo" hospital, Monza and University of Milano-Bicocca, Milan, Italy.
Barbara BorroniMolecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.
Michael WagnerGerman Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.ORCID http://orcid.org/0000-0003-2589-6440
Benedetta NacmiasDepartment of Neuroscience, Psychology, Drug Research and Child Health University of Florence, Florence, Italy.ORCID http://orcid.org/0000-0001-9338-9040
Marco SpallazziDepartment of Medicine and Surgery, Unit of Neurology, University-Hospital of Parma, Parma, Italy.
Davide SeripaDepartment of Hematology and Stem Cell Transplant, Vito Fazzi Hospital, Lecce, Italy.
Innocenzo RaineroDepartment of Neuroscience "Rita Levi Montalcini", University of Torino, Torino, Italy.
Antonio DanieleDepartment of Neuroscience, Università Cattolica del Sacro Cuore, Rome, Italy.
Fabrizio PirasLaboratory of Neuropsychiatry, IRCCS Santa Lucia Foundation, Rome, Italy.ORCID http://orcid.org/0000-0003-3566-5494
Carlo MasulloInstitute of Neurology, Catholic University of the Sacred Heart, Rome, Italy.
Giacomina RossiUnit of Neurology V - Neuropathology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.ORCID http://orcid.org/0000-0001-6680-2725
Frank JessenGerman Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
Patrick KehoeTranslational Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.ORCID http://orcid.org/0000-0002-7542-1139
Tsolaki Magda1st Department of Neurology, Medical school, Aristotle University of Thessaloniki, Thessaloniki, Makedonia, Greece.ORCID http://orcid.org/0000-0002-2072-8010
Pascual Sánchez-JuanCIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain.
Kristel SleegersComplex Genetics of Alzheimer's Disease Group, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium.ORCID http://orcid.org/0000-0002-0283-2332
Martin IngelssonDept. of Public Health and Caring Sciences / Geriatrics, Uppsala University, Uppsala, Sweden.ORCID http://orcid.org/0000-0001-5466-8370
Mikko HiltunenInstitute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
Rebecca SimsCentre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neuroscience, School of Medicine, Cardiff University, Cardiff, UK.ORCID http://orcid.org/0000-0002-3885-1199
Wiesje van der FlierAlzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.ORCID http://orcid.org/0000-0001-8766-6224
Ole A AndreassenNORMENT Centre, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.ORCID http://orcid.org/0000-0002-4461-3568
Agustín RuizCIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain.ORCID http://orcid.org/0000-0003-2633-2495
Alfredo RamirezDivision of Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.ORCID http://orcid.org/0000-0003-4991-763X
EADB
Ruth Frikke-SchmidtDepartment of Clinical Biochemistry, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.ORCID http://orcid.org/0000-0003-4084-5027
Najaf AminNuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.ORCID http://orcid.org/0000-0002-8944-1771
Gennady RoshchupkinDepartment of Epidemiology, Erasmus MC, Rotterdam, The Netherlands.ORCID http://orcid.org/0000-0002-3403-2313
Jean-Charles LambertUniv. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, LabEx DISTALZ - U1167-RID-AGE Facteurs de risque et déterminants moléculaires des maladies liées au vieillissement, Lille, France.ORCID http://orcid.org/0000-0003-0829-7817
Kristel Van SteenBIO3 - Systems Medicine, Department of Human Genetics, KU Leuven, Leuven, Belgium. kristel.vansteen@uliege.be.ORCID http://orcid.org/0000-0001-9868-5033
Cornelia van DuijnNuffield Department of Population Health, University of Oxford, Oxford, United Kingdom. cornelia.vanduijn@ndph.ox.ac.uk.ORCID http://orcid.org/0000-0002-2374-9204
Valentina Escott-PriceSchool of Medicine, Cardiff University, Cardiff, UK. EscottPriceV@cardiff.ac.uk.ORCID http://orcid.org/0000-0003-1784-5483
Funding
RCUK | Medical Research Council (MRC) UK DRI-3206
Abstract
Traditional statistical approaches have advanced our understanding of the genetics of complex diseases, yet are limited to linear additive models. Here we applied machine learning (ML) to genome-wide data from 41,686 individuals in the largest European consortium on Alzheimer's disease (AD) to investigate the effectiveness of various ML algorithms in replicating known findings, discovering novel loci, and predicting individuals at risk. We utilised Gradient Boosting Machines (GBMs), biological pathway-informed Neural Networks (NNs), and Model-based Multifactor Dimensionality Reduction (MB-MDR) models. ML approaches successfully captured all genome-wide significant genetic variants identified in the training set and 22% of associations from larger meta-analyses. They highlight 6 novel loci which replicate in an external dataset, including variants which map to ARHGAP25, LY6H, COG7, SOD1 and ZNF597. They further identify novel association in AP4E1, refining the genetic landscape of the known SPPL2A locus. Our results demonstrate that machine learning methods can achieve predictive performance comparable to classical approaches in genetic epidemiology and have the potential to uncover novel loci that remain undetected by traditional GWAS. These insights provide a complementary avenue for advancing the understanding of AD genetics.
Indexed as
Alzheimer DiseaseMachine LearningAlgorithmsGenetic Predisposition to DiseaseGenome-Wide Association StudyGTPase-Activating ProteinsHumansNeural Networks, ComputerPolymorphism, Single NucleotideGTPase-Activating Proteins
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