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

Kun-Rodrigues, Celia ; Londos, Elisabet LU and Bras, Jose (2019) In Neurobiology of Aging 75. p.1-223
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... (More)
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. © 2018 (Less)
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author
author collaboration
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Copy number variants, Dementia with Lewy bodies, Genome-wide, MAPT, SNCA
in
Neurobiology of Aging
volume
75
pages
1 - 223
publisher
Elsevier
external identifiers
  • scopus:85056701141
  • pmid:30448004
ISSN
1558-1497
DOI
10.1016/j.neurobiolaging.2018.10.019
language
English
LU publication?
yes
additional info
Export Date: 29 November 2018 Article in Press
id
d63e62df-5250-441d-bdae-6d923eaeb794
date added to LUP
2018-11-29 08:26:32
date last changed
2020-02-19 05:13:46
@article{d63e62df-5250-441d-bdae-6d923eaeb794,
  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. © 2018},
  author       = {Kun-Rodrigues, Celia and Londos, Elisabet and Bras, Jose},
  issn         = {1558-1497},
  language     = {eng},
  pages        = {1--223},
  publisher    = {Elsevier},
  series       = {Neurobiology of Aging},
  title        = {A comprehensive screening of copy number variability in dementia with Lewy bodies},
  url          = {http://dx.doi.org/10.1016/j.neurobiolaging.2018.10.019},
  doi          = {10.1016/j.neurobiolaging.2018.10.019},
  volume       = {75},
  year         = {2019},
}