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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Journal article |
| Idioma: | English |
| Publicado em: |
Elsevier
2018
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| _version_ | 1826285000818950144 |
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| author | 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 Clarimon, 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 |
| 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 Clarimon, 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 |
| author_sort | Kun-Rodrigues, C |
| collection | OXFORD |
| 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. |
| first_indexed | 2024-03-07T01:22:18Z |
| format | Journal article |
| id | oxford-uuid:90c523a4-4918-461c-8a0c-3a2c3fdf91a0 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T01:22:18Z |
| publishDate | 2018 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oxford-uuid:90c523a4-4918-461c-8a0c-3a2c3fdf91a02022-03-26T23:14:13ZA comprehensive screening of copy number variability in dementia with Lewy bodiesJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:90c523a4-4918-461c-8a0c-3a2c3fdf91a0EnglishSymplectic ElementsElsevier2018Kun-Rodrigues, COrme, TCarmona, SHernandez, DGRoss, OAEicher, JDShepherd, CParkkinen, LDarwent, LHeckman. MGScholz, SWTroncoso. JCPletnikova. ODawson, TRosenthal, LAnsorge, OClarimon, JLleo, AMorenas-Rodriguez, EClark, L Honig, LSMarder, KLemstra, ARogaeva, ESt George-Hyslop, P Londos, EZetterberg, HBarber, IBraae, ABrown, KMorgan, KTroakes, CAl-Sarraj, SLashley, THolton, JCompta, YVan Deerlin, VSerrano, GEBeach, TGLesage, SGalasko, DMasliah, ESantana, IPastor, P Diez-Fairen, MAguilar, MTienari, PJMyllykangas, LOinas, MRevesz, TThe 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. |
| spellingShingle | 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 Clarimon, 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 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 |
| 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_short | A comprehensive screening of copy number variability in dementia with Lewy bodies |
| title_sort | comprehensive screening of copy number variability in dementia with lewy bodies |
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