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Longitudinal change in memory performance as a strong endophenotype for Alzheimer's disease.
Archer, Derek B; Eissman, Jaclyn M; Mukherjee, Shubhabrata; Lee, Michael L; Choi, Seo-Eun; Scollard, Phoebe; Trittschuh, Emily H; Mez, Jesse B; Bush, William S; Kunkle, Brian W; Naj, Adam C; Gifford, Katherine A; Cuccaro, Michael L; Pericak-Vance, Margaret A; Farrer, Lindsay A; Wang, Li-San; Schellenberg, Gerard D; Mayeux, Richard P; Haines, Jonathan L; Jefferson, Angela L; Kukull, Walter A; Keene, C Dirk; Saykin, Andrew J; Thompson, Paul M; Martin, Eden R; Bennett, David A; Barnes, Lisa L; Schneider, Julie A; Crane, Paul K; Dumitrescu, Logan; Hohman, Timothy J.
Afiliação
  • Archer DB; Vanderbilt Memory & Alzheimer's Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
  • Eissman JM; Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
  • Mukherjee S; Vanderbilt Memory & Alzheimer's Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
  • Lee ML; Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
  • Choi SE; Department of Medicine, University of Washington, Seattle, Washington, USA.
  • Scollard P; Department of Medicine, University of Washington, Seattle, Washington, USA.
  • Trittschuh EH; Department of Medicine, University of Washington, Seattle, Washington, USA.
  • Mez JB; Department of Medicine, University of Washington, Seattle, Washington, USA.
  • Bush WS; Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, Washington, USA.
  • Kunkle BW; VA Puget Sound Health Care System, GRECC, Seattle, Washington, USA.
  • Naj AC; Department of Neurology, Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts, USA.
  • Gifford KA; Cleveland Institute for Computational Biology, Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, Ohio, USA.
  • Cuccaro ML; Vanderbilt Memory & Alzheimer's Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
  • Schellenberg GD; John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA.
  • Mayeux RP; John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA.
  • Haines JL; Department of Neurology, Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts, USA.
  • Jefferson AL; Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA.
  • Kukull WA; Department of Medicine (Biomedical Genetics), Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts, USA.
  • Keene CD; Penn Neurodegeneration Genomics Center, Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
  • Saykin AJ; Penn Neurodegeneration Genomics Center, Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
  • Thompson PM; Columbia University, New York, New York, USA.
  • Martin ER; The Taub Institute for Research on Alzheimer's Disease and The Aging Brain, Columbia University, New York, New York, USA.
  • Bennett DA; The Institute for Genomic Medicine, Columbia University Medical Center and The New York Presbyterian Hospital, New York, New York, USA.
  • Barnes LL; Cleveland Institute for Computational Biology, Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, Ohio, USA.
  • Schneider JA; Vanderbilt Memory & Alzheimer's Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
  • Crane PK; Department of Epidemiology, School of Public Health, University of Washington, Seattle, Washington, USA.
  • Dumitrescu L; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA.
  • Hohman TJ; Department of Radiology and Imaging Services, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Alzheimers Dement ; 20(2): 1268-1283, 2024 Feb.
Article em En | MEDLINE | ID: mdl-37985223
ABSTRACT

INTRODUCTION:

Although large-scale genome-wide association studies (GWAS) have been conducted on AD, few have been conducted on continuous measures of memory performance and memory decline.

METHODS:

We conducted a cross-ancestry GWAS on memory performance (in 27,633 participants) and memory decline (in 22,365 participants; 129,201 observations) by leveraging harmonized cognitive data from four aging cohorts.

RESULTS:

We found high heritability for two ancestry backgrounds. Further, we found a novel ancestry locus for memory decline on chromosome 4 (rs6848524) and three loci in the non-Hispanic Black ancestry group for memory performance on chromosomes 2 (rs111471504), 7 (rs4142249), and 15 (rs74381744). In our gene-level analysis, we found novel genes for memory decline on chromosomes 1 (SLC25A44), 11 (BSX), and 15 (DPP8). Memory performance and memory decline shared genetic architecture with AD-related traits, neuropsychiatric traits, and autoimmune traits.

DISCUSSION:

We discovered several novel loci, genes, and genetic correlations associated with late-life memory performance and decline. HIGHLIGHTS Late-life memory has high heritability that is similar across ancestries. We discovered four novel variants associated with late-life memory. We identified four novel genes associated with late-life memory. Late-life memory shares genetic architecture with psychiatric/autoimmune traits.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doença de Alzheimer Limite: Humans Idioma: En Revista: Alzheimers Dement Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doença de Alzheimer Limite: Humans Idioma: En Revista: Alzheimers Dement Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos