Alzheimers Dement
| Autor: | Lori B. Chibnik, Céline Bellenguez, Philippe Amouyel, Andrew J. Saykin, Alden L. Gross, Shubhabrata Mukherjee, Stephen J. Newhouse, Paul K. Crane, Ryan Koesterer, Jorge L. Del-Aguila, Richard Sherva, Leanne Munsie, Ashley R. Winslow, David A. Bennett, Robert C. Green, Carole Dufouil, Richard Mayeux, John S. K. Kauwe, Carlos Cruchaga, Lindsay A. Farrer |
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| Přispěvatelé: | Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM) |
| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Apolipoprotein E Epidemiology Genome-wide association study Biology Article 03 medical and health sciences Cellular and Molecular Neuroscience Chromosome 15 0302 clinical medicine Developmental Neuroscience Alzheimer Disease Humans Cognitive Dysfunction Cognitive decline Gene Aged Genetic association Aged 80 and over Genetics Chromosome 7 (human) Health Policy Genetic Variation Psychiatry and Mental health 030104 developmental biology VINTAGE Chromosome 3 Disease Progression Female [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie Neurology (clinical) Geriatrics and Gerontology 030217 neurology & neurosurgery Genome-Wide Association Study |
| Zdroj: | Alzheimer's and Dementia Alzheimer's and Dementia, Elsevier, 2020, 16 (8), pp.1134-1145. ⟨10.1002/alz.12106⟩ Alzheimers Dement |
| ISSN: | 1552-5279 1552-5260 |
| DOI: | 10.1002/alz.12106 |
| Popis: | 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) e4 and e2 variants, do not have a major impact. |
| Databáze: | OpenAIRE |
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