Portal de investigación
Machine learning in Alzheimer's disease genetics
Fecha de publicación:
Autores de IIS La Fe
Participantes ajenos a IIS La Fe
- Bracher-Smith, Matthew
- Ulm, Brittany
- Bellenguez, Celine
- Grenier-Boley, Benjamin
- Duroux, Diane
- Nevado, Alejo J.
- Holmans, Peter
- Tijms, Betty M.
- de Rojas, Itziar
- Campos-Martin, Rafael
- van der Lee, Sven
- Castillo, Atahualpa
- Kucukali, Fahri
- Peters, Oliver
- Schneider, Anja
- Dichgans, Martin
- Rujescu, Dan
- Scherbaum, Norbert
- Deckert, Juergen
- Riedel-Heller, Steffi
- Hausner, Lucrezia
- Molina-Porcel, Laura
- Duezel, Emrah
- Grimmer, Timo
- Wiltfang, Jens
- Heilmann-Heimbach, Stefanie
- Moebus, Susanne
- Tegos, Thomas
- Scarmeas, Nikolaos
- Dols-Icardo, Oriol
- Moreno, Fermin
- Bullido, Maria J.
- Pastor, Pau
- Alvarez, Victoria
- Rodriguez-Rodriguez, Eloy
- Soininen, Hilkka
- de Mendonca, Alexandre
- Mehrabian, Shima
- Hort, Jakub
- Vyhnalek, Martin
- Sandau, Nicolai
- Thomassen, Jesper Qvist
- Pijnenburg, Yolande A. L.
- Holstege, Henne
- van Swieten, John
- Ramakers, Inez
- Verhey, Frans
- Scheltens, Philip
- Graff, Caroline
- Papenberg, Goran
- Giedraitis, Vilmantas
- Williams, Julie
- Amouyel, Philippe
- Boland, Anne
- Deleuze, Jean-Francois
- Nicolas, Gael
- Dufouil, Carole
- Pasquier, Florence
- Hanon, Olivier
- Debette, Stephanie
- Gruenblatt, Edna
- Popp, Julius
- Solfrizzi, Vincenzo
- Parnetti, Lucilla
- Squassina, Alessio
- Tremolizzo, Lucio
- Borroni, Barbara
- Nacmias, Benedetta
- Spallazzi, Marco
- Seripa, Davide
- Rainero, Innocenzo
- Jessen, Frank
- Kehoe, Patrick
- Magda, Tsolaki
- Sanchez-Juan, Pascual
- Sleegers, Kristel
- Ingelsson, Martin
- Hiltunen, Mikko
- Sims, Rebecca
- van der Flier, Wiesje
- Andreassen, Ole A.
- Ruiz, Agustin
- Ramirez, Alfredo
- Frikke-Schmidt, Ruth
- Amin, Najaf
- Roshchupkin, Gennady
- Lambert, Jean-Charles
- Van Steen, Kristel
- van Duijn, Cornelia
- Escott-Price, Valentina
- Jansen, Iris
- Andrade, Victor
- Fernandez, Victoria
- Dalmasso, Maria-Carolina
- Kleineidam, Luca
- Ahmad, Shahzad
- Aarsland, Dag
- Cano, Amanda
- Abdelnour, Carla
- Alarcon-Martin, Emilio
- Alcolea, Daniel
- Alegret, Montserrat
- Alvarez, Ignacio
- Armstrong, Nicola J.
- Anthoula, Tsolaki
- Appollonio, Ildebrando
- Arcaro, Marina
- Archetti, Silvana
- Arias Pastor, Alfonso
- Athanasiu, Lavinia
- Bailly, Henri
- Banaj, Nerisa
- Belen Pastor, Ana
- Berr, Claudine
- Besse, Celine
- Bessi, Valentina
- Binetti, Giuliano
- Bellini, Sonia
- Bizarro, Alessandra
- Blesa, Rafael
- Boada, Merce
- Boschi, Silvia
- Bossu, Paola
- Brathen, Geir
- Bresner, Catherine
- Brodaty, Henry
- Brookes, Keeley J.
- Buiza-Rueda, Dolores
- Burger, Katharina
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- Calero, Miguel
- Chene, Genevieve
- Carracedo, Angel
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- Ciccone, Simona
- Claassen, Jurgen A. H. R.
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- Clark, Christopher
- Conti, Elisa
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- Giuffre, Guido Maria
- Custodero, Carlo
- Daian, Delphine
- Dardiotis, Efthimios
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- de Deyn, Peter Paul
- del Ser, Teodoro
- Denning, Nicola
- Diehl-Schmid, Janine
- Diez-Fairen, Monica
- Rossi, Paolo Dionigi
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- Farotti, Lucia
- Fenoglio, Chiara
- Fernandez-Fuertes, Marta
- Ferreira, Catarina B.
- Ferri, Evelyn
- Fin, Bertrand
- Fischer, Peter
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- Fliessbach, Klaus
- Fortea, Juan
- Foroud, TatianaM.
- Fostinelli, Silvia
- Fox, Nick C.
- Franco-Macias, Emlio
- Frank-Garcia, Ana
- Froelich, Lutz
- Garcia-Gonzalez, Pablo
- Garcia-Madrona, Sebastian
- Garcia-Ribas, Guillermo
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- Giorgio, Giaccone
- Goldhardt, Oliver
- Gonzalez-Perez, Antonio
- Grande, Giulia
- Green, Emma
- Grunblatt, Edna
- Guetta-Baranes, Tamar
- Haapasalo, Annakaisa
- Hadjigeorgiou, Georgios
- Hampel, Harald
- Hardy, John
- Hartmann, Annette M.
- Leonenko, Ganna
- Harwood, Janet
- Helisalmi, Seppo
- Heneka, Michael T.
- Hernandez, Isabel
- Herrmann, Martin J.
- Hoffmann, Per
- Holmes, Clive
- Vilas, Raquel Huerto
- Hulsman, Marc
- Biessels, Geert Jan
- Johansson, Charlotte
- Kilander, Lena
- Stahlbom, Anne Kinhult
- Kivipelto, Miia
- Koivisto, Anne
- Kornhuber, Johannes
- Kosmidis, Mary H.
- Lage, Carmen
- Laukka, Erika J.
- Lauria, Alessandra
- Lehtisalo, Jenni
- Lerch, Ondrej
- Lleo, Alberto
- de Munain, Adolfo Lopez
- Love, Seth
- Lowemark, Malin
- Luckcuck, Lauren
- Macias, Juan
- MacLeod, Catherine A.
- Maier, Wolfgang
- Mangialasche, Francesca
- Marco, Spallazzi
- Marquie, Marta
- Marshall, Rachel
- Martin Montes, Angel
- Martinez Rodriguez, Carmen
- Mead, Simon
- Medina, Miguel
- Meggy, Alun
- Mendoza, Silvia
- Menendez-Gonzalez, Manuel
- Mol, Merel
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- Morgan, Kevin
- Nothen, Markus M.
- Ngandu, Tiia
- Nordestgaard, Borge G.
- Olaso, Robert
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- Orsini, Michela
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- Pineda, Juan A.
- Pisanu, Claudia
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- Quintela, Ines
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- Reinders, Marcel J. T.
- Riederer, Peter
- Olive, Claudia
- Rongve, Arvid
- Rosas Allende, Irene
- Rosende-Roca, Maitee
- Luis Royo, Jose
- Rubino, Elisa
- Eugenia Saez, Maria
- Sakka, Paraskevi
- Saltvedt, Ingvild
- Garcia-Gutierrez, Fernando
- Sanchez-Arjona, Maria Bernal
- Sanchez-Garcia, Florentino
- Sanchez-Valle, Raquel
- Sando, Sigrid B.
- Scamosci, Michela
- Scarpini, Elio
- Scherer, Martin
- Schmid, Matthias
- Schott, Jonathan M.
- Selbaek, Geir
- Shadrin, Alexey A.
- Skrobot, Olivia
- Solomon, Alina
- Sorbi, Sandro
- Sotolongo-Grau, Oscar
- Spottke, Annika
- Stordal, Eystein
- Miguel, Andrea
- Tarraga, Lluis
- Tesi, Niccolo
- Thalamuthu, Anbupalam
- Thomas, Tegos
- Traykov, Latchezar
- Tybjaerg-Hansen, Anne
- Uitterlinden, Andre
- Ullgren, Abbe
- Ulstein, Ingun
- Valero, Sergi
- Van Broeckhoven, Christine
- Van Dongen, Jasper
- van Rooij, Jeroen
- Vandenberghe, Rik
- Vidal, Jean-Sebastian
- Vita, Maria Gabriella
- Vogelgsang, Jonathan
- Wagner, Michael
- Wallon, David
- Weinhold, Leonie
- Windle, Gill
- Woods, Bob
- Yannakoulia, Mary
- Zulaica, Miren
- Ghanbari, Mohsen
- Sachdev, Perminder
- Mather, Karen
- Ikram, Mohammad Arfan
- Melograna, Federico
- Heikkinen, Sami
- Arosio, Beatrice
- Masullo, Carlo
- Real, Luis M.
- Pinol-Ripoll, Gerard
- Galimberti, Daniela
- Piras, Fabrizio
- Garcia-Alberca, Jose Maria
- Mecocci, Patrizia
- Rossi, Giacomina
- Ghidoni, Roberta
- Daniele, Antonio
- EADB
Grupos
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.
©TheAuthor(s)2025,correctedpublication2025
Datos de la publicación
- ISSN/ISSNe:
- 2041-1723, 2041-1723
- Tipo:
- Article
- Páginas:
- -
- PubMed:
- 40691194
- Factor de Impacto:
- 4,846 SCImago ℠
- Cuartil:
- Q1 SCImago ℠
Nature Communications NATURE PORTFOLIO
Citas Recibidas en Web of Science: 8
Documentos
- No hay documentos
Filiaciones
Keywords
- GENOME-WIDE ASSOCIATION; MULTIFACTOR DIMENSIONALITY REDUCTION; RISK LOCI; METAANALYSIS; EPISTASIS; PROTEIN; AGE
Cita
Bracher M,Ulm B,Bellenguez C,Grenier B,Duroux D,Nevado AJ,Holmans P,Tijms BM,de Rojas I,Campos R,van der Lee S,Castillo A,Kucukali F,Peters O,Schneider A,Dichgans M,Rujescu D,Scherbaum N,Deckert J,Riedel S,Hausner L,Molina L,Duezel E,Grimmer T,Wiltfang J,Heilmann S,Moebus S,Tegos T,Scarmeas N,Dols O,Moreno F,PEREZ J,Bullido MJ,Pastor P,Alvarez V,Rodriguez E,Soininen H,de Mendonca A,Mehrabian S,Hort J,Vyhnalek M,Sandau N,Thomassen JQ,Pijnenburg YL,Holstege H,van J,Ramakers I,Verhey F,Scheltens P,Graff C,Papenberg G,Giedraitis V,Williams J,Amouyel P,Boland A,Deleuze J,Nicolas G,Dufouil C,Pasquier F,Hanon O,Debette S,Gruenblatt E,Popp J,Solfrizzi V,Parnetti L,Squassina A,Tremolizzo L,Borroni B,Nacmias B,Spallazzi M,Seripa D,Rainero I,Jessen F,Kehoe P,Magda T,Sanchez P,Sleegers K,Ingelsson M,Hiltunen M,Sims R,van der Flier W,Andreassen OA,Ruiz A,Ramirez A,Frikke R,Amin N,Roshchupkin G,Lambert J,Van K,van C,Escott V,Jansen I,Andrade V,Fernandez V,Dalmasso M,Kleineidam L,Ahmad S,Aarsland D,Cano A,Abdelnour C,Alarcon E,Alcolea D,Alegret M,Alvarez I,Armstrong NJ,Anthoula T,Appollonio I,Arcaro M,Archetti S,Arias A,Athanasiu L,Bailly H,Banaj N,BAQUERO M,Belen A,Berr C,Besse C,Bessi V,Binetti G,Bellini S,Bizarro A,Blesa R,Boada M,Boschi S,Bossu P,Brathen G,Bresner C,Brodaty H,Brookes KJ,Buiza D,Burger K,Burholt V,Calero M,Chene G,Carracedo A,Cecchetti R,Cervera L,Charbonnier C,Chillotti C,Ciccone S,Claassen JHR,Clarimon J,Clark C,Conti E,Corma A,Giuffre GM,Custodero C,Daian D,Dardiotis E,Dartigues J,de Deyn PP,del Ser T,Denning N,Diehl J,Diez M,Rossi PD,Djurovic S,Duron E,Engelborghs S,Blazquez J,Ewers M,Fabrizio T,Nielsen SF,Farotti L,Fenoglio C,Fernandez M,Ferreira CB,Ferri E,Fin B,Fischer P,Fladby T,Fliessbach K,Fortea J,Foroud T,Fostinelli S,Fox NC,Franco E,Frank A,Froelich L,Garcia P,Garcia S,Garcia G,Giegling I,Giorgio G,Goldhardt O,Gonzalez A,Grande G,Green E,Grunblatt E,Guetta T,Haapasalo A,Hadjigeorgiou G,Hampel H,Hardy J,Hartmann AM,Leonenko G,Harwood J,Helisalmi S,Heneka MT,Hernandez I,Herrmann MJ,Hoffmann P,Holmes C,Vilas RH,Hulsman M,Biessels GJ,Johansson C,Kilander L,Stahlbom AK,Kivipelto M,Koivisto A,Kornhuber J,Kosmidis MH,Lage C,Laukka EJ,Lauria A,Lehtisalo J,Lerch O,Lleo A,de Munain AL,Love S,Lowemark M,Luckcuck L,Macias J,MacLeod CA,Maier W,Mangialasche F,Marco S,Marquie M,Marshall R,Martin A,Martinez C,Mead S,Medina M,Meggy A,Mendoza S,Menendez M,Mol M,Montrreal L,Morgan K,Nothen MM,Ngandu T,Nordestgaard BG,Olaso R,Orellana A,Orsini M,Capdevila M,Padovani A,Paolo C,Martinez M,Pericard P,Pineda JA,Pisanu C,Polak T,Posthuma D,Priller J,Puerta R,Quenez O,Quintela I,Rabano A,Reinders MJT,Riederer P,Olive C,Rongve A,Rosas I,Rosende M,Luis J,Rubino E,Eugenia M,Sakka P,Saltvedt I,Garcia F,Sanchez MB,Sanchez F,Sanchez R,Sando SB,Scamosci M,Scarpini E,Scherer M,Schmid M,Schott JM,Selbaek G,Shadrin AA,Skrobot O,Solomon A,Sorbi S,Sotolongo O,Spottke A,Stordal E,Miguel A,Tarraga L,Tesi N,Thalamuthu A,Thomas T,Traykov L,Tybjaerg A,Uitterlinden A,Ullgren A,Ulstein I,Valero S,Van C,Van J,van J,Vandenberghe R,Vidal J,Vita MG,Vogelgsang J,Wagner M,Wallon D,Weinhold L,Windle G,Woods B,Yannakoulia M,Zulaica M,Ghanbari M,Sachdev P,Mather K,Ikram MA,Melograna F,Heikkinen S,Arosio B,Masullo C,Real LM,Pinol G,Galimberti D,Piras F,Garcia JM,Mecocci P,Rossi G,MIR P,Ghidoni R,Daniele A,E. Machine learning in Alzheimer's disease genetics. Nat. Commun. 2025. 16. (1):6726. IF:18,100. (1).