A comprehensive screening of copy number variability in dementia with Lewy bodies.
Neurobiol Aging
; 75: 223.e1-223.e10, 2019 03.
Article
em En
| MEDLINE
| ID: mdl-30448004
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.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Proteínas Oncogênicas
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Predisposição Genética para Doença
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Doença por Corpos de Lewy
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Variações do Número de Cópias de DNA
Tipo de estudo:
Diagnostic_studies
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Screening_studies
Limite:
Aged80
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article