Genome-wide association study of rate of cognitive decline in Alzheimer's disease patients identifies novel genes and pathways
Alzheimers Dement
Document type :
Article dans une revue scientifique: Article original
DOI :
Title :
Genome-wide association study of rate of cognitive decline in Alzheimer's disease patients identifies novel genes and pathways
Alzheimers Dement
Alzheimers Dement
Alternative title :
Alzheimers Dement
Author(s) :
Sherva, R. [Auteur]
Gross, A. [Auteur]
Mukherjee, S. [Auteur]
Koesterer, R. [Auteur]
Amouyel, P. [Auteur]
Bellenguez, C. [Auteur]
Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 [RID-AGE]
Dufouil, Carole [Auteur]
Bordeaux population health [BPH]
Bennett, D. A. [Auteur]
Chibnik, L. [Auteur]
Cruchaga, C. [Auteur]
Del-Aguila, J. [Auteur]
Farrer, L. A. [Auteur]
Mayeux, R. [Auteur]
Munsie, L. [Auteur]
Winslow, A. [Auteur]
Newhouse, S. [Auteur]
Saykin, A. J. [Auteur]
Kauwe, J. S. K. [Auteur]
Crane, P. K. [Auteur]
Green, R. C. [Auteur]
Gross, A. [Auteur]
Mukherjee, S. [Auteur]
Koesterer, R. [Auteur]
Amouyel, P. [Auteur]
Bellenguez, C. [Auteur]
Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 [RID-AGE]
Dufouil, Carole [Auteur]
Bordeaux population health [BPH]
Bennett, D. A. [Auteur]
Chibnik, L. [Auteur]
Cruchaga, C. [Auteur]
Del-Aguila, J. [Auteur]
Farrer, L. A. [Auteur]
Mayeux, R. [Auteur]
Munsie, L. [Auteur]
Winslow, A. [Auteur]
Newhouse, S. [Auteur]
Saykin, A. J. [Auteur]
Kauwe, J. S. K. [Auteur]
Crane, P. K. [Auteur]
Green, R. C. [Auteur]
Journal title :
Alzheimer's & dementia : the journal of the Alzheimer's Association
Pages :
1134-1145
Publisher :
Alzheimer's Association / Wiley
Publication date :
2020
ISSN :
1552-5260
Keyword(s) :
VINTAGE
HAL domain(s) :
Sciences du Vivant [q-bio]/Santé publique et épidémiologie
English abstract : [en]
IntroductionVariability 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.MethodsWe tested ...
Show more >IntroductionVariability 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.MethodsWe 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.ResultsSuggestive 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.DiscussionPathways 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.Show less >
Show more >IntroductionVariability 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.MethodsWe 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.ResultsSuggestive 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.DiscussionPathways 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.Show less >
Language :
Anglais
Peer reviewed article :
Oui
Audience :
Internationale
Popular science :
Non
ANR Project :
Collections :
Source :