RT Journal Article
T1 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.
A1 Moreno-Grau, Sonia
A1 de Rojas, Itziar
A1 Hernández, Isabel
A1 Quintela, Inés
A1 Montrreal, Laura
A1 Alegret, Montserrat
A1 Hernández-Olasagarre, Begoña
A1 Madrid, Laura
A1 González-Perez, Antonio
A1 Maroñas, Olalla
A1 Rosende-Roca, Maitée
A1 Mauleón, Ana
A1 Vargas, Liliana
A1 Lafuente, Asunción
A1 Abdelnour, Carla
A1 Rodríguez-Gómez, Octavio
A1 Gil, Silvia
A1 Santos-Santos, Miguel Ángel
A1 Espinosa, Ana
A1 Ortega, Gemma
A1 Sanabria, Ángela
A1 Pérez-Cordón, Alba
A1 Cañabate, Pilar
A1 Moreno, Mariola
A1 Preckler, Silvia
A1 Ruiz, Susana
A1 Aguilera, Nuria
A1 Pineda, Juan Antonio
A1 Macías, Juan
A1 Alarcón-Martín, Emilio
A1 Sotolongo-Grau, Oscar
A1 GR@ACE consortium, 
A1 DEGESCO consortium, 
A1 Alzheimer's Disease Neuroimaging Initiative, 
A1 Marquié, Marta
A1 Monté-Rubio, Gemma
A1 Valero, Sergi
A1 Benaque, Alba
A1 Clarimón, Jordi
A1 Bullido, Maria Jesus
A1 García-Ribas, Guillermo
A1 Pástor, Pau
A1 Sánchez-Juan, Pascual
A1 Álvarez, Victoria
A1 Piñol-Ripoll, Gerard
A1 García-Alberca, Jose Maria
A1 Royo, José Luis
A1 Franco, Emilio
A1 Mir, Pablo
A1 Calero, Miguel
A1 Medina, Miguel
A1 Rábano, Alberto
A1 Ávila, Jesús
A1 Antúnez, Carmen
A1 Real, Luis Miguel
A1 Orellana, Adelina
A1 Carracedo, Ángel
A1 Sáez, María Eugenia
A1 Tárraga, Lluís
A1 Boada, Mercè
A1 Ruiz, Agustín
K1 Alzheimer's disease
K1 Biological pathway
K1 Cerebral amyloid angiopathy
K1 GWAS
K1 Vascular pathology
AB Large variability among Alzheimer's disease (AD) cases might impact genetic discoveries and complicate dissection of underlying biological pathways. 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. 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. 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.
YR 2019
FD 2019-08-28
LK http://hdl.handle.net/10668/14463
UL http://hdl.handle.net/10668/14463
LA en
DS RISalud
RD Apr 12, 2025