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Title: Genome-wide association analysis of dementia and its clinical endophenotypes reveal novel loci associated with Alzheimer's disease and three causality networks: The GR@ACE project.
Author: Moreno-Grau, Sonia
de Rojas, Itziar
Hernández, Isabel
Quintela, Inés
Montrreal, Laura
Alegret, Montserrat
Hernández-Olasagarre, Begoña
Madrid, Laura
González-Perez, Antonio
Maroñas, Olalla
Rosende-Roca, Maitée
Mauleón, Ana
Vargas, Liliana
Lafuente, Asunción
Abdelnour, Carla
Rodríguez-Gómez, Octavio
Gil, Silvia
Santos-Santos, Miguel Ángel
Espinosa, Ana
Ortega, Gemma
Sanabria, Ángela
Pérez-Cordón, Alba
Cañabate González, Mª del Pilar
Moreno, Mariola
Preckler, Silvia
Ruiz, Susana
Aguilera, Nuria
Pineda, Juan Antonio
Macías, Juan
Alarcón-Martín, Emilio
Sotolongo-Grau, Oscar
GR@ACE consortium
DEGESCO consortium
Alzheimer's Disease Neuroimaging Initiative
Marquié, Marta
Monté-Rubio, Gemma
Valero, Sergi
Benaque, Alba
Clarimón, Jordi
Bullido, María Jesús
García-Ribas, Guillermo
Pastor, Pau
Sánchez-Juan, Pascual
Álvarez, Victoria
Piñol-Ripoll, Gerard
García-Alberca, Jose Maria
Royo, José Luis
Franco, Emilio
Mir, Pablo
Calero, Miguel
Medina, Miguel
Rábano, Alberto
Ávila, Jesús
Antúnez, Carmen
Real, Luis Miguel
Orellana, Adelina
Carracedo Álvarez, Ángel
Saéz, Maria Eugenia
Tárrega, Lluís
Boada, Mercè
Ruiz, Agustí
Keywords: Malaltia d'Alzheimer
Malalties cerebrovasculars
Alzheimer's disease
Cerebrovascular disease
Issue Date: 28-Aug-2019
Publisher: Elsevier Masson
Abstract: Introduction: Large variability among Alzheimer's disease (AD) cases might impact genetic discoveries and complicate dissection of underlying biological pathways. Methods: Genome Research at Fundacio ACE (GR@ACE) is a genome-wide study of dementia and its clinical endophenotypes, defined based on AD's clinical certainty and vascular burden. We assessed the impact of known AD loci across endophenotypes to generate loci categories. We incorporated gene coexpression data and conducted pathway analysis per category. Finally, to evaluate the effect of heterogeneity in genetic studies, GR@ACE series were meta-analyzed with additional genome-wide association study data sets. Results: We classified known AD loci into three categories, which might reflect the disease clinical heterogeneity. Vascular processes were only detected as a causal mechanism in probable AD. The meta-analysis strategy revealed the ANKRD31-rs4704171 and NDUFAF6-rs10098778 and confirmed SCIMP-rs7225151 and CD33-rs3865444. Discussion: The regulation of vasculature is a prominent causal component of probable AD. GR@ACE meta-analysis revealed novel AD genetic signals, strongly driven by the presence of clinical heterogeneity in the AD series.
Note: Reproducció del document publicat a:
It is part of: Alzheimer's & Dementia, 2019, vol. 15, num. 10, p. 1333-1347
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ISSN: 1552-5260
Appears in Collections:Articles publicats en revistes (Antropologia Social)

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