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Machine learning in Alzheimer's disease genetics
M. Bracher-Smith, F. Melograna, B. Ulm, C. Bellenguez, B. Grenier-Boley, D. Duroux, AJ. Nevado, P. Holmans, BM. Tijms, M. Hulsman, I. de Rojas, R. Campos-Martin, SV. der Lee, A. Castillo, F. Küçükali, O. Peters, A. Schneider, M. Dichgans, D....
Jazyk angličtina Země Anglie, Velká Británie
Typ dokumentu časopisecké články
Grantová podpora
UK DRI-3206
RCUK | Medical Research Council (MRC)
NLK
Directory of Open Access Journals
od 2015
Free Medical Journals
od 2010
PubMed Central
od 2012
Europe PubMed Central
od 2012
ProQuest Central
od 2019-01-01
Open Access Digital Library
od 2015-01-01
Open Access Digital Library
od 2015-01-01
Medline Complete (EBSCOhost)
od 2012-11-01
Health & Medicine (ProQuest)
od 2019-01-01
ROAD: Directory of Open Access Scholarly Resources
od 2010
Springer Nature OA/Free Journals
od 2010-12-01
Springer Nature - nature.com Journals - Fully Open Access
od 2010-12-01
- MeSH
- algoritmy MeSH
- Alzheimerova nemoc * genetika MeSH
- celogenomová asociační studie MeSH
- genetická predispozice k nemoci MeSH
- jednonukleotidový polymorfismus MeSH
- lidé MeSH
- neuronové sítě MeSH
- proteiny aktivující GTPasu genetika MeSH
- strojové učení * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
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.
ACE Alzheimer Center Barcelona Universitat Internacional de Catalunya Barcelona Spain
Alzheimer Research Center and Memory Clinic Andalusian Institute for Neuroscience Málaga Spain
Alzheimer's Centre Reina Sofia CIEN Foundation ISCIII 28031 Madrid Spain
BIO3 Systems Genetics GIGA R Molecular and Computational Biology University of Liege Liege Belgium
BIO3 Systems Medicine Department of Human Genetics KU Leuven Leuven Belgium
Centre for Artificial Intelligence in Precision Medicine University of Oxford Oxford United Kingdom
Centro de Biología Molecular Severo Ochoa Madrid Spain
CHU de Bordeaux Pole santé publique Bordeaux France
CHUV Old Age Psychiatry Department of Psychiatry Lausanne Switzerland
Clinic of Neurology UH Alexandrovska Medical University Sofia Sofia Bulgaria
Complex Genetics of Alzheimer's Disease Group VIB Center for Molecular Neurology VIB Antwerp Belgium
Department of Biomedical Sciences University of Antwerp Antwerp Belgium
Department of Clinical and Experimental Sciences University of Brescia Brescia Italy
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 University of Copenhagen Copenhagen Denmark
Department of Clinical Sciences and Community Health University of Milan 20122 Milan Italy
Department of Epidemiology Erasmus MC Rotterdam The Netherlands
Department of Epidemiology ErasmusMC Rotterdam The Netherlands
Department of Geriatric Psychiatry University Hospital of Psychiatry Zürich Zürich Switzerland
Department of Hematology and Stem Cell Transplant Vito Fazzi Hospital Lecce Italy
Department of Medicine and Surgery Unit of Neurology University Hospital of Parma Parma Italy
Department of Neurology Bordeaux University Hospital Bordeaux France
Department of Neurology ErasmusMC Rotterdam Netherlands
Department of Neurology Hospital Universitario Donostia San Sebastian Spain
Department of Neurology Medical University Sofia Sofia Bulgaria
Department of Neuroscience Rita Levi Montalcini University of Torino Torino Italy
Department of Neuroscience Università Cattolica del Sacro Cuore Rome Italy
Department of Psychiatry and Psychotherapy University Medical Center Goettingen Goettingen Germany
Department of Radiology and Nuclear Medicine Erasmus MC Rotterdam The Netherlands
Dept of Biomedical Surgical and Dental Sciences University of Milan Milan IT Italy
Dept of Public Health and Caring Sciences Geriatrics Uppsala University Uppsala Sweden
Dept of Public Health and Carins Sciences Geriatrics Uppsala University Uppsala Sweden
Estudios en Neurociencias y Sistemas Complejos CONICET HEC UNAJ Buenos Aires Argentina
Faculty of Medicine University of Lisbon Lisbon Portugal
Fundació Docència i Recerca MútuaTerrassa Terrassa Barcelona Spain
Geriatric Unit Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico 20122 Milan Italy
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
Institut de Recerca Biomedica de Lleida Lleida Spain
Institute for Stroke and Dementia Research University Hospital LMU Munich Munich Germany
Institute for Urban Public Health University Hospital of 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 Neurology Catholic University of the Sacred Heart Rome Italy
Instituto de Investigacion Sanitaria 'Hospital la Paz' Madrid Spain
Instituto de Investigación Sanitaria del Principado de Asturias Asturias Spain
International Clinical Research Center St Anne's University Hospital Brno Brno Czech Republic
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 Neuropsychiatry IRCCS Santa Lucia Foundation Rome Italy
Medical Science Department iBiMED Aveiro Portugal
Munich Cluster for Systems Neurology Munich Germany
Networking Research Center on Neurodegenerative Diseases Instituto de Salud Carlos 3 Madrid Spain
Neurodegenerative Diseases Unit Fondazione IRCCS Ca' Granda Ospedale Policlinico Milan IT Italy
Neurological Tissue Bank Biobank Hospital Clinic FRCB IDIBAPS Barcelona Spain
Neurology Service Marqués de Valdecilla University Hospital Santander Spain
Neurology Unit IRCCS Fondazione Policlinico Universitario A Gemelli Rome Italy
Neurology Unit San Gerardo hospital Monza and University of Milano Bicocca Milan Italy
Neuroscience Center Zurich University of Zurich and ETH Zurich Zurich Switzerland
Neurosciences Area Instituto Biogipuzkoa San Sebastian Spain
NORMENT Centre Division of Mental Health and Addiction Oslo University Hospital Oslo Norway
Nuffield Department of Population Health University of Oxford Oxford United Kingdom
Old Age Psychiatry Department of Psychiatry Lausanne University Hospital Lausanne Switzerland
School of Medicine Cardiff University Cardiff UK
Translational Health Sciences Bristol Medical School University of Bristol Bristol UK
Unit of Neurology 5 Neuropathology Fondazione IRCCS Istituto Neurologico Carlo Besta Milan Italy
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 de Paris EA 4468 APHP Hôpital Broca Paris France
Université Paris Saclay CEA Centre National de Recherche en Génomique Humaine 91057 Evry France
University Bordeaux Inserm Bordeaux Population Health Research Center Bordeaux France
Zurich Center for Integrative Human Physiology University of Zurich Zurich Switzerland
Citace poskytuje Crossref.org
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
- $a Papenberg, Goran $u Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet and Stockholm University, Stockholm, Sweden
- 700 1_
- $a Giedraitis, Vilmantas $u Dept.of Public Health and Carins Sciences / Geriatrics, Uppsala University, Uppsala, Sweden $1 https://orcid.org/0000000334232021
- 700 1_
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- 700 1_
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- 700 1_
- $a Boland, Anne $u Université Paris-Saclay, CEA, Centre National de Recherche en Génomique Humaine, 91057, Evry, France $1 https://orcid.org/0000000187895676
- 700 1_
- $a Deleuze, Jean-François $u Université Paris-Saclay, CEA, Centre National de Recherche en Génomique Humaine, 91057, Evry, France
- 700 1_
- $a Nicolas, Gael $u Univ Rouen Normandie, Normandie Univ, Inserm U1245 and CHU Rouen, Department of Genetics and CNRMAJ, F-, 76000, Rouen, France $1 https://orcid.org/0000000193917800
- 700 1_
- $a Dufouil, Carole $u Inserm, Bordeaux Population Health Research Center, UMR 1219, Univ. Bordeaux, ISPED, CIC 1401-EC, Univ Bordeaux, Bordeaux, France $u CHU de Bordeaux, Pole santé publique, Bordeaux, France $1 https://orcid.org/0000000324424476
- 700 1_
- $a Pasquier, Florence $u Univ Lille Inserm 1171, CHU Clinical and Research Memory Research Centre (CMRR) of Distalz Lille France, Lille, France $1 https://orcid.org/0000000198809788
- 700 1_
- $a Hanon, Olivier $u Université de Paris, EA 4468, APHP, Hôpital Broca, Paris, France
- 700 1_
- $a Debette, Stéphanie $u University Bordeaux, Inserm, Bordeaux Population Health Research Center, Bordeaux, France $u Department of Neurology, Bordeaux University Hospital, Bordeaux, France $1 https://orcid.org/0000000186757968
- 700 1_
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- 700 1_
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- 700 1_
- $a Ghidoni, Roberta $u Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy $1 https://orcid.org/0000000276911957
- 700 1_
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- 700 1_
- $a Arosio, Beatrice $u Department of Clinical Sciences and Community Health, University of Milan, 20122, Milan, Italy $u Geriatric Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122, Milan, Italy $1 https://orcid.org/0000000206153580
- 700 1_
- $a Mecocci, Patrizia $u Institute of Gerontology and Geriatrics, Department of Medicine and Surgery, University of Perugia, Perugia, Italy $u Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden $1 https://orcid.org/0000000307295246
- 700 1_
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- 700 1_
- $a Parnetti, Lucilla $u Centre for Memory Disturbances, Lab of Clinical Neurochemistry, Section of Neurology, University of Perugia, Perugia, Italy $1 https://orcid.org/0000000157223967
- 700 1_
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- 700 1_
- $a Tremolizzo, Lucio $u Neurology Unit, "San Gerardo" hospital, Monza and University of Milano-Bicocca, Milan, Italy
- 700 1_
- $a Borroni, Barbara $u Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy $u Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
- 700 1_
- $a Wagner, Michael $u German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany $u Department of Cognitive Disorders and Old Age Psychiatry, University Hospital Bonn, Medical Faculty, Bonn, Germany $1 https://orcid.org/0000000325896440
- 700 1_
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- 700 1_
- $a Spallazzi, Marco $u Department of Medicine and Surgery, Unit of Neurology, University-Hospital of Parma, Parma, Italy
- 700 1_
- $a Seripa, Davide $u Department of Hematology and Stem Cell Transplant, Vito Fazzi Hospital, Lecce, Italy
- 700 1_
- $a Rainero, Innocenzo $u Department of Neuroscience "Rita Levi Montalcini", University of Torino, Torino, Italy
- 700 1_
- $a Daniele, Antonio $u Department of Neuroscience, Università Cattolica del Sacro Cuore, Rome, Italy $u Neurology Unit, IRCCS Fondazione Policlinico Universitario A. Gemelli, Rome, Italy
- 700 1_
- $a Piras, Fabrizio $u Laboratory of Neuropsychiatry, IRCCS Santa Lucia Foundation, Rome, Italy $1 https://orcid.org/0000000335665494
- 700 1_
- $a Masullo, Carlo $u Institute of Neurology, Catholic University of the Sacred Heart, Rome, Italy
- 700 1_
- $a Rossi, Giacomina $u Unit of Neurology V - Neuropathology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy $1 https://orcid.org/0000000166802725
- 700 1_
- $a Jessen, Frank $u German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany $u Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany $u Cluster of Excellence Cellular Stress Responses in Aging-associated Diseases (CECAD), University of Cologne, Cologne, Germany
- 700 1_
- $a Kehoe, Patrick $u Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK $1 https://orcid.org/0000000275421139
- 700 1_
- $a Magda, Tsolaki $u 1st Department of Neurology, Medical school, Aristotle University of Thessaloniki, Thessaloniki, Makedonia, Greece $u Laboratory of Genetics, Immunology and Human Pathology, Faculty of Science of Tunis, University of Tunis El Manar, 2092, Tunis, Tunisia $1 https://orcid.org/0000000220728010
- 700 1_
- $a Sánchez-Juan, Pascual $u CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain $u Alzheimer's Centre Reina Sofia-CIEN Foundation-ISCIII, 28031, Madrid, Spain
- 700 1_
- $a Sleegers, Kristel $u Complex Genetics of Alzheimer's Disease Group, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium $u Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium $1 https://orcid.org/0000000202832332
- 700 1_
- $a Ingelsson, Martin $u Dept. of Public Health and Caring Sciences / Geriatrics, Uppsala University, Uppsala, Sweden $u Krembil Brain Institute, University Health Network, Toronto, Ontario, Canada $u Tanz Centre for Research in Neurodegenerative Diseases, Departments of Medicine and Laboratory Medicine & Pathobiology, University of Toronto, Toronto, Ontario, Canada $1 https://orcid.org/0000000154668370
- 700 1_
- $a Hiltunen, Mikko $u Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland
- 700 1_
- $a Sims, Rebecca $u Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neuroscience, School of Medicine, Cardiff University, Cardiff, UK $1 https://orcid.org/0000000238851199
- 700 1_
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- 700 1_
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- 700 1_
- $a Ruiz, Agustín $u CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain $u Research Center and Memory clinic Fundació ACE, Institut Català de Neurociències Aplicades, Universitat Internacional de Catalunya, Barcelona, Spain $u Biggs Institute for Alzheimer's and Neurodegenerative Diseases, University of Texas Health Science Center, San Antonio, Texas, USA $1 https://orcid.org/0000000326332495
- 700 1_
- $a Ramirez, Alfredo $u Division of Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany $u German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany $u Department of Cognitive Disorders and Old Age Psychiatry, University Hospital Bonn, Medical Faculty, Bonn, Germany $u Department of Psychiatry & Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, San Antonio, TX, USA $u Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Disease (CECAD), University of Cologne, Cologne, Germany $1 https://orcid.org/000000034991763X
- 700 1_
- $a Frikke-Schmidt, Ruth $u Department of Clinical Biochemistry, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark $u Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark $1 https://orcid.org/0000000340845027
- 700 1_
- $a Amin, Najaf $u Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom $1 https://orcid.org/0000000289441771
- 700 1_
- $a Roshchupkin, Gennady $u Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands $u Department of Radiology and Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands $1 https://orcid.org/0000000234032313
- 700 1_
- $a Lambert, Jean-Charles $u Univ. 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 $1 https://orcid.org/0000000308297817
- 700 1_
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- 700 1_
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- 700 1_
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