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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 Cardiel, 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 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 Tárraga, Lluís Boada, Mercè Ruiz, Agustín |
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: https://doi.org/10.1016/j.jalz.2019.06.4950 |
It is part of: | Alzheimer's & Dementia, 2019, vol. 15, num. 10, p. 1333-1347 |
URI: | http://hdl.handle.net/2445/170945 |
Related resource: | https://doi.org/10.1016/j.jalz.2019.06.4950 |
ISSN: | 1552-5260 |
Appears in Collections: | Articles publicats en revistes (Antropologia Social) |
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