Genome‐wide association study of rate of cognitive decline in Alzheimer's disease patients identifies novel genes and pathways. Issue 8 (23rd June 2020)

• Record Type: Journal Article
• Authors: Sherva, Richard; Gross, Alden; Mukherjee, Shubhabrata; Koesterer, Ryan; Amouyel, Philippe; Bellenguez, Celine; Dufouil, Carole; Bennett, David A.; Chibnik, Lori; Cruchaga, Carlos; del‐Aguila, Jorge; Farrer, Lindsay A.; Mayeux, Richard; Munsie, Leanne; Winslow, Ashley; Newhouse, Stephen; Saykin, Andrew J.; Kauwe, John S.K.; Crane, Paul K.; Green, Robert C.
• Is Part Of: Alzheimer's & dementia. Volume 16:Issue 8(2020)
• Page Start: 1134
• Page End: 1145
• Publication Date: 2020-06-23
• Subjects: cognitive decline -- disease progression -- genetic association -- pathway analysis; Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.12106
• Languages: English
• ISSNs: 1552-5260

Abstract

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.