Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/12785
Título
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.
Autor(es)
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, Pilar | Moreno, Mariola | Preckler, Silvia | Ruiz, Susana | Aguilera, Nuria | Pineda, Juan Antonio | Macías, Juan | Alarcón-Martín, Emilio | Sotolongo-Grau, Oscar | Marquié, Marta | Monté-Rubio, Gemma | Valero, Sergi | Benaque, Alba | Clarimón, Jordi | Bullido, Maria Jesus | García-Ribas, Guillermo | Pástor, Pau | Sánchez-Juan, Pascual | Álvarez, Victoria | Piñol-Ripoll, Gerard | García-Alberca, Jose Maria | Royo, José Luis | Franco, Emilio | Mir, Pablo | Calero, Miguel ISCIII | Medina, Miguel | Rábano, Alberto | Ávila, Jesús | Antúnez, Carmen | Real, Luis Miguel | Orellana, Adelina | Carracedo, Ángel | Sáez, María Eugenia | Tárraga, Lluís | Boada, Mercè | Ruiz, Agustín
Fecha de publicación
2019
Cita
Alzheimers Dement . 2019 Oct;15(10):1333-1347.
Idioma
Inglés
Tipo de documento
journal article
Resumen
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.
Palabras clave
MESH
Endophenotypes | Genetic Loci | Genome-Wide Association Study | Aged | Alzheimer Disease | Dementia | Female | Genetic Predisposition to Disease | Humans | Male | Middle Aged | Polymorphism, Single Nucleotide | Spain
Versión en línea
DOI
Aparece en las colecciones
- Investigación > ISCIII > Unidad Funcional de Investigación de Enfermedades Crónicas (UFIEC)
- Investigación > IIS > IDIVAL - Instituto de Investigación Marqués de Valdecilla (Cantabria)
- Investigación > IIS > IRB LÉRIDA - Instituto de Investigación Biomédica de Lérida (Cataluña)
- Investigación > IIS > ISPA - Instituto de Investigación Sanitaria del Principado de Asturias (Asturias)
- Investigación > IIS > IBIS - Instituto de Biomedicina de Sevilla (Andalucía)
- Investigación > IIS > IdiPAZ - Instituto de Investigación Sanitaria Hospital La Paz (Madrid)
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