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Somatic Loss of the Y Chromosome and Alzheimer’s Disease Risk

Ellen Palmer, Penelope Benchek, Nicholas Wheeler, View ORCID ProfileSandra Smeiszek, View ORCID ProfileAdam C. Naj, Jonathan L. Haines, Margaret A. Pericak-Vance, Lars A. Forsberg, Holly N. Cukier, Yeunjoo Song, View ORCID ProfileWilliam S. Bush
doi: https://doi.org/10.1101/2022.11.14.516433
Ellen Palmer
1Cleveland Institute for Computational Biology, Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH
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Penelope Benchek
1Cleveland Institute for Computational Biology, Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH
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Nicholas Wheeler
1Cleveland Institute for Computational Biology, Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH
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Sandra Smeiszek
1Cleveland Institute for Computational Biology, Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH
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  • ORCID record for Sandra Smeiszek
Adam C. Naj
2Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Philadelphia, Pennsylvania, USA
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Jonathan L. Haines
1Cleveland Institute for Computational Biology, Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH
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Margaret A. Pericak-Vance
3John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA
4John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, Florida, USA
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Lars A. Forsberg
5Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, 75108 Uppsala, Sweden
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Holly N. Cukier
3John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA
4John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, Florida, USA
6Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, USA
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Yeunjoo Song
1Cleveland Institute for Computational Biology, Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH
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William S. Bush
1Cleveland Institute for Computational Biology, Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH
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  • ORCID record for William S. Bush
  • For correspondence: wsb36@case.edu
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Abstract

Mosaic loss of the Y chromosome (LOY) is a somatic, age-related event that has been previously associated with a variety of diseases of aging. A prior study of European cohorts demonstrated an association between LOY and Alzheimer’s Disease and more recent molecular studies have shown that LOY can also occur within microglia, suggesting a potential functional role in AD pathogenesis. In this study, we further validate the association between LOY and AD via prospective analyses of 1,447 males, and perform Mendelian Randomization analysis on 10,013 males across 26 US cohorts. Significant results from these analyses provide further evidence for a role of LOY in the development of Alzheimer’s Disease.

Competing Interest Statement

L.A.F. is cofounder and shareholder of Cray Innovation AB. The remaining authors declare no competing interests.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted November 16, 2022.
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Somatic Loss of the Y Chromosome and Alzheimer’s Disease Risk
Ellen Palmer, Penelope Benchek, Nicholas Wheeler, Sandra Smeiszek, Adam C. Naj, Jonathan L. Haines, Margaret A. Pericak-Vance, Lars A. Forsberg, Holly N. Cukier, Yeunjoo Song, William S. Bush
bioRxiv 2022.11.14.516433; doi: https://doi.org/10.1101/2022.11.14.516433
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Somatic Loss of the Y Chromosome and Alzheimer’s Disease Risk
Ellen Palmer, Penelope Benchek, Nicholas Wheeler, Sandra Smeiszek, Adam C. Naj, Jonathan L. Haines, Margaret A. Pericak-Vance, Lars A. Forsberg, Holly N. Cukier, Yeunjoo Song, William S. Bush
bioRxiv 2022.11.14.516433; doi: https://doi.org/10.1101/2022.11.14.516433

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