Sex‐specific genetic architecture of late‐life memory performance-Reference-Cited by-同舟云学术

Sex‐specific genetic architecture of late‐life memory performance

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

Author:

Eissman Jaclyn M.¹²^ORCID,Archer Derek B.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,Cruchaga Carlos¹¹¹²,Pericak‐Vance Margaret A.⁸,Farrer Lindsay A.⁶¹³¹⁴,Wang Li‐San¹⁰,Schellenberg Gerard D.¹⁰,Mayeux Richard P.¹⁵¹⁶¹⁷,Haines Jonathan L.⁷,Jefferson Angela L.¹,Kukull Walter A.¹⁸,Keene C. Dirk¹⁹,Saykin Andrew J.²⁰²¹,Thompson Paul M.²²,Martin Eden R.⁸,Bennett David A.²³,Barnes Lisa L.²³,Schneider Julie A.²³,Crane Paul K.³,Hohman Timothy J.¹²,Dumitrescu Logan¹²,

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 Psychiatry Washington University School of Medicine St Louis Missouri USA

12. NeuroGenomics and Informatics Center Washington University School of Medicine St. Louis Missouri USA

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

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

15. Columbia University New York New York USA

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

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

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

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

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

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

22. Keck School of Medicine University of Southern California Los Angeles California USA

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

Abstract

AbstractBACKGROUNDWomen demonstrate a memory advantage when cognitively healthy yet lose this advantage to men in Alzheimer's disease. However, the genetic underpinnings of this sex difference in memory performance remain unclear.METHODSWe conducted the largest sex‐aware genetic study on late‐life memory to date (Nmales = 11,942; Nfemales = 15,641). Leveraging harmonized memory composite scores from four cohorts of cognitive aging and AD, we performed sex‐stratified and sex‐interaction genome‐wide association studies in 24,216 non‐Hispanic White and 3367 non‐Hispanic Black participants.RESULTSWe identified three sex‐specific loci (rs67099044—CBLN2, rs719070—SCHIP1/IQCJ‐SCHIP), including an X‐chromosome locus (rs5935633—EGL6/TCEANC/OFD1), that associated with memory. Additionally, we identified heparan sulfate signaling as a sex‐specific pathway and found sex‐specific genetic correlations between memory and cardiovascular, immune, and education traits.DISCUSSIONThis study showed memory is highly and comparably heritable across sexes, as well as highlighted novel sex‐specific genes, pathways, and genetic correlations that related to late‐life memory.Highlights

Demonstrated the heritable component of late‐life memory is similar across sexes.

Identified two genetic loci with a sex‐interaction with baseline memory.

Identified an X‐chromosome locus associated with memory decline in females.

Highlighted sex‐specific candidate genes and pathways associated with memory.

Revealed sex‐specific shared genetic architecture between memory and complex 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

Link

https://alz-journals.onlinelibrary.wiley.com/doi/pdf/10.1002/alz.13507

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