Machine learning in Alzheimer’s disease genetics

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 inves...

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Main Authors:	Bracher-Smith, Matthew (Author) , Melograna, Federico (Author) , Ulm, Brittany (Author) , Bellenguez, Céline (Author) , Grenier-Boley, Benjamin (Author) , Duroux, Diane (Author) , Nevado, Alejo J. (Author) , Holmans, Peter (Author) , Tijms, Betty M. (Author) , Hulsman, Marc (Author) , Rojas, Itziar de (Author) , Campos Martín, Rafael (Author) , Lee, Sven J. van der (Author) , Castillo, Atahualpa (Author) , Küçükali, Fahri (Author) , Peters, Oliver Hubertus (Author) , Schneider, Anja (Author) , Dichgans, Martin (Author) , Rujescu, Dan (Author) , Scherbaum, Norbert (Author) , Deckert, Jürgen (Author) , Riedel-Heller, Steffi Gerlinde (Author) , Hausner, Lucrezia (Author) , Molina-Porcel, Laura (Author) , Düzel, Emrah (Author) , Grimmer, Timo (Author) , Wiltfang, Jens (Author) , Heilmann-Heimbach, Stefanie (Author) , Moebus, Susanne (Author) , Tegos, Thomas (Author) , Scarmeas, Nikolaos (Author) , Dols-Icardo, Oriol (Author) , Moreno, Fermin (Author) , Pérez-Tur, Jordi (Author) , Bullido, María J. (Author) , Pastor, Pau (Author) , Sánchez-Valle, Raquel (Author) , Álvarez, Victoria (Author) , Boada, Mercè (Author) , García-González, Pablo (Author) , Puerta, Raquel (Author) , Mir, Pablo (Author) , Real, Luis M. (Author) , Piñol-Ripoll, Gerard (Author) , García-Alberca, Jose María (Author) , Rodriguez-Rodriguez, Eloy (Author) , Soininen, Hilkka (Author) , Heikkinen, Sami (Author) , Mendonça, Alexandre de (Author) , Mehrabian, Shima (Author) , Traykov, Latchezar (Author) , Hort, Jakub (Author) , Vyhnalek, Martin (Author) , Sandau, Nicolai (Author) , Thomassen, Jesper Qvist (Author) , Pijnenburg, Yolande A. L. (Author) , Holstege, Henne (Author) , Swieten, John C. van (Author) , Ramakers, Inez (Author) , Verhey, Frans (Author) , Scheltens, Philip (Author) , Graff, Caroline (Author) , Papenberg, Goran (Author) , Giedraitis, Vilmantas (Author) , Williams, Julie (Author) , Amouyel, Philippe (Author) , Boland, Anne (Author) , Deleuze, Jean-François (Author) , Nicolas, Gaël (Author) , Dufouil, Carole (Author) , Pasquier, Florence (Author) , Hanon, Olivier (Author) , Debette, Stéphanie (Author) , Grünblatt, Edna (Author) , Popp, Julius Daniel (Author) , Ghidoni, Roberta (Author) , Galimberti, Daniela (Author) , Arosio, Beatrice (Author) , Mecocci, Patrizia (Author) , Solfrizzi, Vincenzo (Author) , Parnetti, Lucilla (Author) , Squassina, Alessio (Author) , Tremolizzo, Lucio (Author) , Borroni, Barbara (Author) , Wagner, Michael (Author) , Nacmias, Benedetta (Author) , Spallazzi, Marco (Author) , Seripa, Davide (Author) , Rainero, Innocenzo (Author) , Daniele, Antonio (Author) , Piras, Fabrizio (Author) , Masullo, Carlo (Author) , Rossi, Giacomina (Author) , Jessen, Frank (Author) , Kehoe, Patrick (Author) , Tsolaki, Magda (Author) , Sánchez-Juan, Pascual (Author) , Sleegers, Kristel (Author) , Ingelsson, Martin (Author) , Hiltunen, Mikko (Author) , Sims, Rebecca (Author) , Flier, Wiesje Maria van der (Author) , Andreassen, Ole A. (Author) , Ruiz, Agustín (Author) , Ramírez, Alfredo (Author) , Frikke-Schmidt, Ruth (Author) , Amin, Najaf (Author) , Roshchupkin, Gennady (Author) , Lambert, Jean-Charles (Author) , Steen, Kristel Van (Author) , Duijn, Cornelia van (Author) , Escott-Price, Valentina (Author) , Frölich, Lutz (Author)
Format:	Article (Journal)
Language:	English
Published:	22 July 2025
In:	Nature Communications Year: 2025, Volume: 16, Pages: 1-16
ISSN:	2041-1723
DOI:	10.1038/s41467-025-61650-z
Online Access:	Verlag, kostenfrei: https://pmc.ncbi.nlm.nih.gov/articles/PMC12280214/ Verlag, kostenfrei: https://www.nature.com/articles/s41467-025-61650-z Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s41467-025-61650-z
Author Notes:	Matthew Bracher-Smith, Federico Melograna, Brittany Ulm, Céline Bellenguez, Benjamin Grenier-Boley, Diane Duroux, Alejo J. Nevado, Peter Holmans, Betty M. Tijms, Marc Hulsman, Itziar de Rojas, Rafael Campos-Martin, Sven van der Lee, Atahualpa Castillo, Fahri Küçükali, Oliver Peters, Anja Schneider, Martin Dichgans, Dan Rujescu, Norbert Scherbaum, Jürgen Deckert, Steffi Riedel-Heller, Lucrezia Hausner, Laura Molina-Porcel, Emrah Düzel, Timo Grimmer, Jens Wiltfang, Stefanie Heilmann-Heimbach, Susanne Moebus, Thomas Tegos, Nikolaos Scarmeas, Oriol Dols-Icardo, Fermin Moreno, Jordi Pérez-Tur, María J. Bullido, Pau Pastor, Raquel Sánchez-Valle, Victoria Álvarez, Mercè Boada, Pablo García-González, Raquel Puerta, Pablo Mir, Luis M. Real, Gerard Piñol-Ripoll, Jose María García-Alberca, Eloy Rodriguez-Rodriguez, Hilkka Soininen, Sami Heikkinen, Alexandre de Mendonça, Shima Mehrabian, Latchezar Traykov, Jakub Hort, Martin Vyhnalek, Nicolai Sandau, Jesper Qvist Thomassen, Yolande A.L. Pijnenburg, Henne Holstege, John van Swieten, Inez Ramakers, Frans Verhey, Philip Scheltens, Caroline Graff, Goran Papenberg, Vilmantas Giedraitis, Julie Williams, Philippe Amouyel, Anne Boland, Jean-François Deleuze, Gael Nicolas, Carole Dufouil, Florence Pasquier, Olivier Hanon, Stéphanie Debette, Edna Grünblatt, Julius Popp, Roberta Ghidoni, Daniela Galimberti, Beatrice Arosio, Patrizia Mecocci, Vincenzo Solfrizzi, Lucilla Parnetti, Alessio Squassina, Lucio Tremolizzo, Barbara Borroni, Michael Wagner, Benedetta Nacmias, Marco Spallazzi, Davide Seripa, Innocenzo Rainero, Antonio Daniele, Fabrizio Piras, Carlo Masullo, Giacomina Rossi, Frank Jessen, Patrick Kehoe, Tsolaki Magda, Pascual Sánchez-Juan, Kristel Sleegers, Martin Ingelsson, Mikko Hiltunen, Rebecca Sims, Wiesje van der Flier, Ole A. Andreassen, Agustín Ruiz, Alfredo Ramirez, Ruth Frikke-Schmidt, Najaf Amin, Gennady Roshchupkin, Jean-Charles Lambert, Kristel Van Steen, Cornelia van Duijn & Valentina Escott-Price