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Journal Articles Neurobiology of Aging Year : 2019

A comprehensive screening of copy number variability in dementia with Lewy bodies

Dena Hernandez
  • Function : Author
Elisabet Londos
  • Function : Author
Anne Braae
Vivianna van Deerlin
Geidy Serrano
  • Function : Author
Thomas Beach
  • Function : Author
Isabel Santana
  • Function : Author
Pau Pastor
Valentina Escott-Price
Dennis Dickson
Andrew Singleton
  • Function : Author
Rita Guerreiro

Abstract

The role of genetic variability in dementia with Lewy bodies (DLB) is now indisputable; however, data regarding copy number variation (CNV) in this disease has been lacking. Here, we used whole-genome genotyping of 1454 DLB cases and 1525 controls to assess copy number variability. We used 2 algorithms to confidently detect CNVs, performed a case-control association analysis, screened for candidate CNVs previously associated with DLB-related diseases, and performed a candidate gene approach to fully explore the data. We identified 5 CNV regions with a significant genome-wide association to DLB; 2 of these were only present in cases and absent from publicly available databases: one of the regions overlapped LAPTM4B, a known lysosomal protein, whereas the other overlapped the NME1 locus and SPAG9. We also identified DLB cases presenting rare CNVs in genes previously associated with DLB or related neurodegenerative diseases, such as SNCA, APP, and MAPT. To our knowledge, this is the first study reporting genome-wide CNVs in a large DLB cohort. These results provide preliminary evidence for the contribution of CNVs in DLB risk.

Dates and versions

hal-04556394 , version 1 (23-04-2024)

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Celia Kun-Rodrigues, Tatiana Orme, Susana Carmona, Dena Hernandez, Owen Ross, et al.. A comprehensive screening of copy number variability in dementia with Lewy bodies. Neurobiology of Aging, 2019, 75, pp.223.e1-223.e10. ⟨10.1016/j.neurobiolaging.2018.10.019⟩. ⟨hal-04556394⟩
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