Titre :

Genome‐wide association study of rate of cognitive decline in Alzheimer's disease patients identifies novel genes and pathways

Auteur(s) :

Sherva, Richard [Auteur]
Gross, Alden [Auteur]
Mukherjee, Shubhabrata [Auteur]
Koesterer, Ryan [Auteur]
Amouyel, Philippe [Auteur]
Bellenguez, Celine [Auteur]
Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 [RID-AGE]
Dufouil, Carole [Auteur]
Bennett, David [Auteur]
Chibnik, Lori [Auteur]
Cruchaga, Carlos [Auteur]
Del-Aguila, Jorge [Auteur]
Farrer, Lindsay [Auteur]
Mayeux, Richard [Auteur]
Munsie, Leanne [Auteur]
Winslow, Ashley [Auteur]
Newhouse, Stephen [Auteur]
Saykin, Andrew [Auteur]
Kauwe, John S.K. [Auteur]
Crane, Paul [Auteur]
Green, Robert [Auteur]

Titre de la revue :

Alzheimer's & dementia : the journal of the Alzheimer's Association

Pagination :

1134-1145

Éditeur :

Alzheimer's Association / Wiley

Date de publication :

2020-08

ISSN :

1552-5260

Discipline(s) HAL :

Sciences du Vivant [q-bio]

Résumé en anglais : [en]

Abstract Introduction Variability exists in the disease trajectories of Alzheimer's disease (AD) patients. We performed a genome‐wide association study to examine rate of cognitive decline (ROD) in patients with AD. Methods ...
Lire la suite >Abstract Introduction Variability exists in the disease trajectories of Alzheimer's disease (AD) patients. We performed a genome‐wide association study to examine rate of cognitive decline (ROD) in patients with AD. Methods We tested for interactions between genetic variants and time since diagnosis to predict the ROD of a composite cognitive score in 3946 AD cases and performed pathway analysis on the top genes. Results Suggestive associations ( P < 1.0 × 10 −6 ) were observed on chromosome 15 in DNA polymerase‐γ (rs3176205, P = 1.11 × 10 −7 ), chromosome 7 (rs60465337, P = 4.06 × 10 −7 ) in contactin‐associated protein‐2, in RP11‐384F7.1 on chromosome 3 (rs28853947, P = 5.93 × 10 −7 ), family with sequence similarity 214 member‐A on chromosome 15 (rs2899492, P = 5.94 × 10 −7 ), and intergenic regions on chromosomes 16 (rs4949142, P = 4.02 × 10 −7 ) and 4 (rs1304013, P = 7.73 × 10 −7 ). Significant pathways involving neuronal development and function, apoptosis, memory, and inflammation were identified. Discussion Pathways related to AD, intelligence, and neurological function determine AD progression, while previously identified AD risk variants, including the apolipoprotein ( APOE ) ε4 and ε2 variants, do not have a major impact.Lire moins >

Langue :

Anglais

Comité de lecture :

Oui

Audience :

Internationale

Vulgarisation :

Non

Collections :

• Facteurs de risque et déterminants moléculaires des maladies liées au vieillissement (RID-AGE) - U1167

Source :

Harvested from HAL