학술논문

Longitudinal change in memory performance as a strong endophenotype for Alzheimer's disease.
Document Type
Academic Journal
Author
Archer DB; Vanderbilt Memory & Alzheimer's Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA.; Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, Tennessee, USA.; Eissman JM; Vanderbilt Memory & Alzheimer's Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA.; Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, Tennessee, USA.; Mukherjee S; Department of Medicine, University of Washington, Seattle, Washington, USA.; Lee ML; Department of Medicine, University of Washington, Seattle, Washington, 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 Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, Washington, USA.; VA Puget Sound Health Care System, GRECC, Seattle, Washington, USA.; Mez JB; Department of Neurology, Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts, USA.; Bush WS; Cleveland Institute for Computational Biology, Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, Ohio, USA.; Kunkle BW; John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA.; Naj AC; Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.; Penn Neurodegeneration Genomics Center, Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.; Gifford KA; Vanderbilt Memory & Alzheimer's Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA.; Cuccaro ML; John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA.; Pericak-Vance MA; John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA.; Farrer LA; Department of Neurology, Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts, USA.; Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA.; Department of Medicine (Biomedical Genetics), Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts, USA.; Wang LS; Penn Neurodegeneration Genomics Center, Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.; Schellenberg GD; Penn Neurodegeneration Genomics Center, Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.; Mayeux RP; Columbia University, New York, New York, USA.; The Taub Institute for Research on Alzheimer's Disease and The Aging Brain, Columbia University, New York, New York, USA.; The Institute for Genomic Medicine, Columbia University Medical Center and The New York Presbyterian Hospital, New York, New York, USA.; Haines JL; Cleveland Institute for Computational Biology, Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, Ohio, USA.; Jefferson AL; Vanderbilt Memory & Alzheimer's Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA.; Kukull WA; Department of Epidemiology, School of Public Health, University of Washington, Seattle, Washington, USA.; Keene CD; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA.; Saykin AJ; Department of Radiology and Imaging Services, Indiana University School of Medicine, Indianapolis, Indiana, USA.; Department of Medical and Molecular Genetics, School of Medicine, Indiana University, Indianapolis, Indiana, USA.; Indiana Alzheimer's Disease Research Center, Indiana University School of Medicine, Indianapolis, Indiana, USA.; Thompson PM; Imaging Genetics Center, Stevens Neuroimaging & Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, California, USA.; Martin ER; John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA.; Bennett DA; Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois, USA.; Barnes LL; Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois, USA.; Schneider JA; Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois, USA.; Crane PK; Department of Medicine, University of Washington, Seattle, Washington, USA.; Dumitrescu L; Vanderbilt Memory & Alzheimer's Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA.; Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, Tennessee, USA.; Hohman TJ; Vanderbilt Memory & Alzheimer's Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA.; Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Source
Publisher: John Wiley & Sons, Ltd Country of Publication: United States NLM ID: 101231978 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1552-5279 (Electronic) Linking ISSN: 15525260 NLM ISO Abbreviation: Alzheimers Dement Subsets: MEDLINE
Subject
Language
English
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.
(© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)