A genome‐wide association meta‐analysis of all‐cause and vascular dementia
- Authors: Bernard Fongang, Muralidharan Sargurupremraj, Xueqiu Jian, Aniket Mishra, Vincent Damotte, Itziar de Rojas, Olivia Skrobot, Joshua C. Bis, Kang‐Hsien Fan, Erin Jacobsen, Gloria Hoi‐Yee Li, Jingyun Yang, Bizzarro Alessandra, Lauria Alessandra, Saima Hilal, Joyce Ruifen Chong, Yuek Ling Chai, M. J. Knol, Maria Pina Concas, Girotto Giorgia, Moeen Riaz, Chenglong Yu, Alexander Guojonsson, Paul Lacaze, Adam C Naj, Monica Gireud‐Goss, Yannick N. Wadop, Aicha Soumare, Vincent Bouteloup, Vilmundur Gudnason, Petronilla Battista, Aurora Santin, Beatrice Spedicati, Rodolfo Sardone, Lenore Launer, Jan Bressler, Rebecca F Gottesman, Quentin Le Grand, Ilana Caro, Gennady V. Roshchupkin, Hampton L. Leonard, Chaojie Yang, Traci M. Bartz, Constance Bordes, Paul M. Ridker, Mirjam I. Geerlings, Natalie C. Gasca, Ani Manichaikul, Mike A. Nalls, Stephen S. Rich, Carsten O. Schmidt, Stella Trompet, Jessica van Setten, Marion van Vugt, Hans J. Grabe, J Wouter Jukema, Ina L. Rissanen, Sylvia Wassertheil‐Smoller, M. Arfan Ikram, Eleanor M. Simonsick, W T. Longstreth, Daniel I. Chasman, Jerome I. Rotter, Naveed Sattar, David J Stott, Eric J Shiroma, Sigurdur Sigurdsson, Mohsen Ghanbari, Ulf Schminke, Eric Boerwinkle, Hugo J Aparicio, Alexa S Beiser, Jose R Romero, Vasileios Lioutas, Ruiqi Wang, Chloe Sarnowski, Alexander Teumer, Uwe Völker, Thomas H. Mosley, Marta Marquié, Pablo García‐González, Clàudia Olivé, Raquel Puerta, Amanda Cano, Oscar Sotolongo‐Grau, Sergi Valero, Vanesa Veronica Pytel, Maitée Rosende‐Roca, Montserrat Alegret, Lluís Tàrraga, Mercè Boada, Ángel Carracedo, Emilio Franco‐Macías, Gerard Piñol‐Ripoll, Guillermo Garcia‐Ribas, Jordi Pérez‐Tur, Jose Luís Royo, Jose María García‐Alberca, Luis Miguel Real, María Eugenia Sáez, María J. Bullido, Miguel Calero, Miguel Medina, Pablo Mir, Pascual Sánchez‐Juan, Pau Pastor, Victoria Álvarez, Benjamin Grenier‐Boley, Fahri Küçükali, Sven Van der Lee, Oliver Peters, Anja Schneider, Martin Dichgans, Dan Rujescu, Jürgen Deckert, Emrah Düzel, Jens Wiltfang, Michael Wagner, Timo Grimmer, Nikolaos Scarmeas, Fermin Moreno, Raquel Sánchez‐Valle, Luis M Real, Eloy Rodriguez‐Rodriguez, Adolfo Lopez de Munain, Alexandre de Mendonça, Jakub Hort, Caroline Graff, Goran Papenberg, Vilmantas Giedraitis, Børge G. Nordestgaard, Hilkka Soininen, Miia Kivipelto, Annakaisa Haapasalo, Gael Nicolas, Florence Pasquier, Olivier Hanon, Edna Grünblatt, Daniela Galimberti, Beatrice Arosio, Patrizia Mecocci, Alessio Squassina, Lucio Tremolizzo, Innocenzo Rainero, Davide Seripa, Julie Williams, Philippe Amouyel, Frank Jessen, Tsolaki Magda, Ruth Frikke‐Schmidt, Kristel Sleegers, Sebastiaan Engelborghs, Rik Vandenberghe, Martin Ingelsson, Giacomina Rossi, Mikko Hiltunen, Rebecca Sims, Magdalena Gugała‐Iwaniuk, Mitchell K. P. Lai, Venketasubramanian N, Boon‐Yeow Tan, Angelo Baldassare Cefalu', Nicola J Armstrong, Roberta Baschi, Regis bordet , Anne‐Marie Bordet, Henry Brodaty, Srdjan Djurovic, Grazia D'Onofrio, Margaret Esiri, Patrick Gelé, Teresa Juarez‐Cedillo, Raj Kalaria, Pekka Karhunen, Jan LACZO, Ondrej LERCH, Carlo Masullo, Karen A Mather, Vaclav MATOSKA, Susanna Melkas, Roberto Monastero, Katya Numbers, Francesco Panza, Tuomo M Polvikoski, Joe Quinn, Arvid Rongve, Perminder S Sachdev, Michela Scamosci, Anbupalam Thalamuthu, Anne Tybjærg‐Hansen, Martin VYHNALEK, Shawn K. Westaway, Amy E Martinsen, Anne Heidi Skogholt, Cristen J Willer, Eystein Stordal, Geir Bråthen, Jonas Bille Nielsen, Lars G Fritsche, Laurent F Thomas, Linda M Pedersen, Maiken E Gabrielsen, Ole Kristian Drange, Sigrid Botne Sando, Tore Wergeland Meisingset, Genevieve Chene, Wei Zhou, Christophe Tzourio, Adrienne Tin, Oscar L Lopez, Haan Mary, Allison E Aiello, Sigrid Børte, Ingunn Bosnes, Cornelia van Duijn, Ching‐Lung Cheung, David A Bennett, Christopher Chen, M. Ilyas Kamboh, Claudia Satizabal, M. Kamran Ikram, Hieab Adams, Yang Qiong, Gerard D. Schel
- Publication year: 2024
- Type: Articolo in rivista
- OA Link: http://hdl.handle.net/10447/665371
Abstract
INTRODUCTION: Dementia is a multifactorial disease with Alzheimer's disease (AD) and vascular dementia (VaD) pathologies making the largest contributions. Yet, most genome-wide association studies (GWAS) focus on AD. METHODS: We conducted a GWAS of all-cause dementia (ACD) and examined the genetic overlap with VaD. Our dataset includes 800,597 individuals, with 46,902 and 8702 cases of ACD and VaD, respectively. Known AD loci for ACD and VaD were replicated. Bioinformatic analyses prioritized genes that are likely functionally relevant and shared with closely related traits and risk factors. RESULTS: For ACD, novel loci identified were associated with energy transport (SEMA4D), neuronal excitability (ANO3), amyloid deposition in the brain (RBFOX1), and magnetic resonance imaging markers of small vessel disease (SVD; HBEGF). Novel VaD loci were associated with hypertension, diabetes, and neuron maintenance (SPRY2, FOXA2, AJAP1, and PSMA3). DISCUSSION: Our study identified genetic risks underlying ACD, demonstrating overlap with neurodegenerative processes, vascular risk factors, and cerebral SVD. Highlights: We conducted the largest genome-wide association study of all-cause dementia (ACD) and vascular dementia (VaD). Known genetic variants associated with AD were replicated for ACD and VaD. Functional analyses identified novel loci for ACD and VaD. Genetic risks of ACD overlapped with neurodegeneration, vascular risk factors, and cerebral small vessel disease.