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Genome-wide association study of rate of cognitive decline in Alzheimer's disease patients identifies novel genes and pathways.
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.
Afiliação
  • Sherva R; Department of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, Massachusetts, USA.
  • Gross A; Johns Hopkins Bloomberg School of Public Health, Johns Hopkins Center on Aging and Health, Baltimore, Maryland, USA.
  • Mukherjee S; Department of Medicine, University of Washington, Seattle, Washington, USA.
  • Koesterer R; Programs in Metabolism and Medical & Population Genetics, Broad Institute, Cambridge, Massachusetts, USA.
  • Amouyel P; Inserm, CHU Lille, Institute Pasteur de Lille, U1167 - RID-AGE - Risk factors and molecular determinants of age-related diseases; Institute Pasteur de Lille, University of Lille, Lille Cedex, France.
  • Bellenguez C; Institut Pasteur de Lille, Lille, France.
  • Dufouil C; DISTALZ Laboratory of Excellence (LabEx), University of Lille, Lille, France.
  • Bennett DA; Inserm, CHU Lille, Institute Pasteur de Lille, U1167 - RID-AGE - Risk factors and molecular determinants of age-related diseases; Institute Pasteur de Lille, University of Lille, Lille Cedex, France.
  • Chibnik L; Institut Pasteur de Lille, Lille, France.
  • Cruchaga C; DISTALZ Laboratory of Excellence (LabEx), University of Lille, Lille, France.
  • Del-Aguila J; Inserm Unit 1219 Bordeaux Population Health, CIC 1401-EC (Clinical Epidemiology), University of Bordeaux, ISPED (Bordeaux School of Public Health), Bordeaux University Hospital, Bordeaux, France.
  • Farrer LA; Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois, USA.
  • Mayeux R; Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, USA.
  • Munsie L; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
  • Winslow A; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
  • Newhouse S; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, Missouri, USA.
  • Saykin AJ; Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA.
  • Kauwe JSK; Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, Missouri, USA.
  • Crane PK; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, Missouri, USA.
  • Green RC; Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA.
Alzheimers Dement ; 16(8): 1134-1145, 2020 08.
Article em En | MEDLINE | ID: mdl-32573913
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doença de Alzheimer / Disfunção Cognitiva Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Aged / Aged80 / Female / Humans / Male Idioma: En Revista: Alzheimers Dement Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doença de Alzheimer / Disfunção Cognitiva Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Aged / Aged80 / Female / Humans / Male Idioma: En Revista: Alzheimers Dement Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Estados Unidos