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

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 algorit...

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Detalles Bibliográficos
Autores: Kun-Rodrigues, C, Orme, T, Carmona, S, Hernandez, DG, Ross, OA, Eicher, JD, Shepherd, C, Parkkinen, L, Darwent, L, Heckman, MG, Scholz, SW, Troncoso, JC, Pletnikova, O, Dawson, T, Rosenthal, L, Ansorge, O, Clarimonm, J, Lleo, A, Morenas-Rodriguez, E, Clark, L, Honig, LS, Marder, K, Lemstra, A, Rogaeva, E, St George-Hyslop, P, Londos, E, Zetterberg, H, Barber, I, Braae, A, Brown, K, Morgan, K, Troakes, C, Al-Sarraj, S, Lashley, T, Holton, J, Compta, Y, Van Deerlin, V, Serrano, GE, Beach, TG, Lesage, S, Galasko, D, Masliah, E, Santana, I, Pastor, P, Diez-Fairen, M, Aguilar, M, Tienari, PJ, Myllykangas, L, Oinas, M, Revesz, T, Lees, A, Boeve, BF, Petersen, RC, Ferman, TJ, Escott-Price, V, Graff-Radford, N, Cairns, NJ, Morris, JC, Pickering-Brown, S, Mann, D, Halliday, GM, Hardy, J, Trojanowski, JQ, Dickson, DW, Singleton, A, Stone, DJ, Guerreiro, R, Bras, J
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Institución:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
Repositorio:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
OAI Identifier:oai:iibsantpau.fundanetsuite.com:p2981
Acceso en línea:https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=2981
http://hdl.handle.net/10400.4/2247
Access Level:acceso abierto
Palabra clave:Dementia with Lewy bodies
Copy number variants
MAPT
SNCA
Genome-wide
Descripción
Sumario: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. (C) 2019 Elsevier Inc. All rights reserved.

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