Longitudinal change in memory performance as a strong endophenotype for Alzheimer's disease-Reference-Cited by-全球学者库

Longitudinal change in memory performance as a strong endophenotype for Alzheimer's disease

Published:2023-11-20 Issue: Volume: Page:
ISSN:1552-5260
Container-title:Alzheimer's & Dementia
language:en
Short-container-title:Alzheimer's & Dementia

Author:

Archer Derek B.¹²,Eissman Jaclyn M.¹²,Mukherjee Shubhabrata³,Lee Michael L.³,Choi Seo‐Eun³,Scollard Phoebe³,Trittschuh Emily H.⁴⁵,Mez Jesse B.⁶,Bush William S.⁷,Kunkle Brian W.⁸,Naj Adam C.⁹¹⁰,Gifford Katherine A.¹,Cuccaro Michael L.⁸,Pericak‐Vance Margaret A.⁸,Farrer Lindsay A.⁶¹¹¹²,Wang Li‐San¹⁰,Schellenberg Gerard D.¹⁰,Mayeux Richard P.¹³¹⁴¹⁵,Haines Jonathan L.⁷,Jefferson Angela L.¹,Kukull Walter A.¹⁶,Keene C. Dirk¹⁷,Saykin Andrew J.¹⁸¹⁹²⁰,Thompson Paul M.²¹,Martin Eden R.⁸,Bennett David A.²²,Barnes Lisa L.²²,Schneider Julie A.²²,Crane Paul K.³,Dumitrescu Logan¹²,Hohman Timothy J.¹²^ORCID, , ,

Affiliation:

1. Vanderbilt Memory & Alzheimer's Center Vanderbilt University Medical Center Nashville Tennessee USA

2. Vanderbilt Genetics Institute Vanderbilt University Medical Center Nashville Tennessee USA

3. Department of Medicine University of Washington Seattle Washington USA

4. Department of Psychiatry and Behavioral Sciences University of Washington School of Medicine Seattle Washington USA

5. VA Puget Sound Health Care System GRECC Seattle Washington USA

6. Department of Neurology Boston University Chobanian & Avedisian School of Medicine Boston Massachusetts USA

7. Cleveland Institute for Computational Biology Department of Population and Quantitative Health Sciences Case Western Reserve University Cleveland Ohio USA

8. John P. Hussman Institute for Human Genomics University of Miami Miller School of Medicine Miami Florida USA

9. Department of Biostatistics, Epidemiology, and Informatics University of Pennsylvania Perelman School of Medicine Philadelphia Pennsylvania USA

10. Penn Neurodegeneration Genomics Center Department of Pathology and Laboratory Medicine University of Pennsylvania Perelman School of Medicine Philadelphia Pennsylvania USA

11. Department of Biostatistics Boston University School of Public Health Boston Massachusetts USA

12. Department of Medicine (Biomedical Genetics) Boston University Chobanian & Avedisian School of Medicine Boston Massachusetts USA

13. Columbia University New York New York USA

14. The Taub Institute for Research on Alzheimer's Disease and The Aging Brain Columbia University New York New York USA

15. The Institute for Genomic Medicine Columbia University Medical Center and The New York Presbyterian Hospital New York New York USA

16. Department of Epidemiology School of Public Health University of Washington Seattle Washington USA

17. Department of Laboratory Medicine and Pathology University of Washington Seattle Washington USA

18. Department of Radiology and Imaging Services Indiana University School of Medicine Indianapolis Indiana USA

19. Department of Medical and Molecular Genetics School of Medicine Indiana University Indianapolis Indiana USA

20. Indiana Alzheimer's Disease Research Center Indiana University School of Medicine Indianapolis Indiana USA

21. Imaging Genetics Center Stevens Neuroimaging & Informatics Institute Keck School of Medicine University of Southern California Marina del Rey California USA

22. Rush Alzheimer's Disease Center Rush University Medical Center Chicago Illinois USA

Abstract

AbstractINTRODUCTIONAlthough 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.METHODSWe 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.RESULTSWe 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.DISCUSSIONWe 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.

Funder

National Institutes of Health

U.S. Department of Defense

Publisher

Wiley

Subject

Psychiatry and Mental health,Cellular and Molecular Neuroscience,Geriatrics and Gerontology,Neurology (clinical),Developmental Neuroscience,Health Policy,Epidemiology

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