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

dc.rights.licenseopenen_US
dc.contributor.authorSHERVA, R.
dc.contributor.authorGROSS, A.
dc.contributor.authorMUKHERJEE, S.
dc.contributor.authorKOESTERER, R.
dc.contributor.authorAMOUYEL, Philippe
dc.contributor.authorBELLENGUEZ, C.
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorDUFOUIL, Carole
dc.contributor.authorBENNETT, D. A.
dc.contributor.authorCHIBNIK, L.
dc.contributor.authorCRUCHAGA, C.
dc.contributor.authorDEL-AGUILA, J.
dc.contributor.authorFARRER, L. A.
dc.contributor.authorMAYEUX, R.
dc.contributor.authorMUNSIE, L.
dc.contributor.authorWINSLOW, A.
dc.contributor.authorNEWHOUSE, S.
dc.contributor.authorSAYKIN, A. J.
dc.contributor.authorKAUWE, J. S. K.
dc.contributor.authorCRANE, P. K.
dc.contributor.authorGREEN, R. C.
dc.date.accessioned2021-02-26T11:01:00Z
dc.date.available2021-02-26T11:01:00Z
dc.date.issued2020
dc.identifier.issn1552-5279 (Electronic) 1552-5260 (Linking)en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/26363
dc.description.abstractEnIntroduction 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.
dc.language.isoENen_US
dc.subjectVINTAGE
dc.title.enGenome-wide association study of rate of cognitive decline in Alzheimer's disease patients identifies novel genes and pathways
dc.title.alternativeAlzheimers Dementen_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1002/alz.12106en_US
dc.subject.halSciences du Vivant [q-bio]/Santé publique et épidémiologieen_US
dc.identifier.pubmed32573913en_US
bordeaux.journalAlzheimer's and Dementiaen_US
bordeaux.page1134-1145en_US
bordeaux.volume16en_US
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - U1219en_US
bordeaux.issue8en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.teamVINTAGEen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.identifierhal-03153338
hal.version1
hal.date.transferred2021-02-26T11:01:04Z
hal.exporttrue
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