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Title | Genome-wide association study of rate of cognitive decline in Alzheimer's disease patients identifies novel genes and pathways. |
Publication Type | Journal Article |
Year of Publication | 2020 |
Authors | Sherva R, Gross A, Mukherjee S, Koesterer R, Amouyel P, Bellenguez C, Dufouil C, Bennett DA, Chibnik L, Cruchaga C, Del-Aguila J, Farrer LA, Mayeux R, Munsie L, Winslow A, Newhouse S, Saykin AJ, Kauwe JSK, Crane PK, Green RC |
Corporate Authors | Alzheimer's Disease Genetics Consortium |
Journal | Alzheimers Dement |
Volume | 16 |
Issue | 8 |
Pagination | 1134-1145 |
Date Published | 08/2022 |
ISSN | 1552-5279 |
Keywords | Aged, Aged, 80 and over, Alzheimer Disease, Cognitive Dysfunction, Disease Progression, Female, Genetic Variation, Genome-Wide Association Study, Humans, Male |
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 ) were observed on chromosome 15 in DNA polymerase-γ (rs3176205, P = 1.11 × 10 ), chromosome 7 (rs60465337,P = 4.06 × 10 ) in contactin-associated protein-2, in RP11-384F7.1 on chromosome 3 (rs28853947, P = 5.93 × 10 ), family with sequence similarity 214 member-A on chromosome 15 (rs2899492, P = 5.94 × 10 ), and intergenic regions on chromosomes 16 (rs4949142, P = 4.02 × 10 ) and 4 (rs1304013, P = 7.73 × 10 ). 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. |
DOI | 10.1002/alz.12106 |
Alternate Journal | Alzheimers Dement |
PubMed ID | 32573913 |
PubMed Central ID | PMC7924136 |
Grant List | R01 AG064877 / AG / NIA NIH HHS / United States R01 AG057777 / AG / NIA NIH HHS / United States R01 AG067501 / AG / NIA NIH HHS / United States P50 AG008702 / AG / NIA NIH HHS / United States R01 AG015801 / AG / NIA NIH HHS / United States RF1AG053303 / NH / NIH HHS / United States R01 AG042437 / AG / NIA NIH HHS / United States P30 AG010161 / AG / NIA NIH HHS / United States R01AG05777 / NH / NIH HHS / United States RF1 AG044546 / AG / NIA NIH HHS / United States R01AG044546 / NH / NIH HHS / United States P01AG003991 / NH / NIH HHS / United States P30AG10161 / NH / NIH HHS / United States P01 AG026276 / NH / NIH HHS / United States P30 AG066444 / AG / NIA NIH HHS / United States U01 AG058922 / AG / NIA NIH HHS / United States R01 AG044546 / AG / NIA NIH HHS / United States U24 AG021886 / AG / NIA NIH HHS / United States U01 AG052411 / AG / NIA NIH HHS / United States U01 AG032984 / AG / NIA NIH HHS / United States RF1 AG053303 / AG / NIA NIH HHS / United States P01 AG003991 / AG / NIA NIH HHS / United States P50 AG005681 / AG / NIA NIH HHS / United States U24 AG056270 / AG / NIA NIH HHS / United States P01 AG026276 / AG / NIA NIH HHS / United States R01 AG017917 / AG / NIA NIH HHS / United States RF1 AG058501 / AG / NIA NIH HHS / United States K25 AG055620 / AG / NIA NIH HHS / United States RF1 AG054023 / AG / NIA NIH HHS / United States R01AG058501 / NH / NIH HHS / United States U01AG052411 / NH / NIH HHS / United States R01AG042437 / NH / NIH HHS / United States R01AG15819 / NH / NIH HHS / United States U19 AG066567 / AG / NIA NIH HHS / United States U01AG058922 / NH / NIH HHS / United States R01AG17917 / NH / NIH HHS / United States P50 AG05681 / NH / NIH HHS / United States R01 AG015819 / AG / NIA NIH HHS / United States |