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...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| 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 |
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A comprehensive screening of copy number variability in dementia with Lewy bodiesKun-Rodrigues, COrme, TCarmona, SHernandez, DGRoss, OAEicher, JDShepherd, CParkkinen, LDarwent, LHeckman, MGScholz, SWTroncoso, JCPletnikova, ODawson, TRosenthal, LAnsorge, OClarimonm, JLleo, AMorenas-Rodriguez, EClark, LHonig, LSMarder, KLemstra, ARogaeva, ESt George-Hyslop, PLondos, EZetterberg, HBarber, IBraae, ABrown, KMorgan, KTroakes, CAl-Sarraj, SLashley, THolton, JCompta, YVan Deerlin, VSerrano, GEBeach, TGLesage, SGalasko, DMasliah, ESantana, IPastor, PDiez-Fairen, MAguilar, MTienari, PJMyllykangas, LOinas, MRevesz, TLees, ABoeve, BFPetersen, RCFerman, TJEscott-Price, VGraff-Radford, NCairns, NJMorris, JCPickering-Brown, SMann, DHalliday, GMHardy, JTrojanowski, JQDickson, DWSingleton, AStone, DJGuerreiro, RBras, JDementia with Lewy bodiesCopy number variantsMAPTSNCAGenome-wideThe 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.ELSEVIER SCIENCE INC2019info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=2981http://hdl.handle.net/10400.4/2247NEUROBIOLOGY OF AGINGISSN: 01974580ISSNe: 15581497reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pauinstname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)Inglésinfo:eu-repo/semantics/openAccessoai:iibsantpau.fundanetsuite.com:p29812026-06-14T12:41:47Z |
| dc.title.none.fl_str_mv |
A comprehensive screening of copy number variability in dementia with Lewy bodies |
| title |
A comprehensive screening of copy number variability in dementia with Lewy bodies |
| spellingShingle |
A comprehensive screening of copy number variability in dementia with Lewy bodies Kun-Rodrigues, C Dementia with Lewy bodies Copy number variants MAPT SNCA Genome-wide |
| title_short |
A comprehensive screening of copy number variability in dementia with Lewy bodies |
| title_full |
A comprehensive screening of copy number variability in dementia with Lewy bodies |
| title_fullStr |
A comprehensive screening of copy number variability in dementia with Lewy bodies |
| title_full_unstemmed |
A comprehensive screening of copy number variability in dementia with Lewy bodies |
| title_sort |
A comprehensive screening of copy number variability in dementia with Lewy bodies |
| dc.creator.none.fl_str_mv |
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 |
| author |
Kun-Rodrigues, C |
| author_facet |
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 |
| author_role |
author |
| author2 |
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 |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
Dementia with Lewy bodies Copy number variants MAPT SNCA Genome-wide |
| topic |
Dementia with Lewy bodies Copy number variants MAPT SNCA Genome-wide |
| description |
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. |
| publishDate |
2019 |
| dc.date.none.fl_str_mv |
2019 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
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article |
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publishedVersion |
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https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=2981 http://hdl.handle.net/10400.4/2247 |
| url |
https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=2981 http://hdl.handle.net/10400.4/2247 |
| dc.language.none.fl_str_mv |
Inglés |
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Inglés |
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info:eu-repo/semantics/openAccess |
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openAccess |
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ELSEVIER SCIENCE INC |
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ELSEVIER SCIENCE INC |
| dc.source.none.fl_str_mv |
NEUROBIOLOGY OF AGING ISSN: 01974580 ISSNe: 15581497 reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau instname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau) |
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Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau) |
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r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau |
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r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau |
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