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

Kun-Rodrigues, Celia; Orme, Tatiana; Carmona, Susana; Hernandez, Dena G; Ross, Owen A; Eicher, John D; Shepherd, Claire; Parkkinen, Laura; Darwent, Lee; Heckman, Michael G; Scholz, Sonja W; Troncoso, Juan C; Pletnikova, Olga; Ansorge, Olaf; Clarimon, Jordi; Lleo, Alberto; Morenas-Rodriguez, Estrella; Clark, Lorraine; Honig, Lawrence S; Marder, Karen; Lemstra, Afina; Rogaeva, Ekaterina; St. George-Hyslop, Peter; Londos, Elisabet; Zetterberg, Henrik; Barber, Imelda; Braae, Anne; Brown, Kristelle; Morgan, Kevin; Troakes, Claire; Al-Sarraj, Safa; Lashley, Tammaryn; Holton, Janice; Compta, Yaroslau; Deerlin, Vivianna Van; Serrano, Geidy E; Beach, Thomas G; Lesage, Suzanne; Galasko, Douglas; Masliah, Eliezer; Santana, Isabel; Pastor, Pau; Diez-Fairen, Monica; Aguilar, Miquel; Tienari, Pentti J; Myllykangas, Liisa; Oinas, Minna; Revesz, Tamas; Lees, Andrew; Boeve, Brad F; Petersen, Ronald C; Ferman, Tanis J; Escott-Price, Valentina; Graff-Radford, Neill; Cairns, Nigel J; Morris, John C; Picke...

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 1,454 DLB cases and 1,525 controls to assess copy number variability. We used two 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 five CNV regions with a significant genome-wide association to DLB, two of these were only present in cases and absent from publicly available databases: one of the regions overlapped LAPTM4B, a known lysosomal protein; whilst the other overlapped the NME1 locus and SPAG9. We also identified DLB cases presenting CNVs in genes previously associated with DLB or related neurodegenerative diseases, namely SNCA and
MAPT. To our knowledge, this is the first study reporting genome-wide CNVs in a large DLB cohort.

Citation

Kun-Rodrigues, C., Orme, T., Carmona, S., Hernandez, D. G., Ross, O. A., Eicher, J. D., …Bras, J. (2019). A comprehensive screening of copy-number variability in dementia with Lewy bodies. Neurobiology of Aging, 75, 223.e1-223.e10. https://doi.org/10.1016/j.neurobiolaging.2018.10.019

• Journal Article Type: Article
• Acceptance Date: Oct 15, 2018
• Online Publication Date: Oct 24, 2018
• Publication Date: 2019-03
• Deposit Date: Nov 1, 2018
• Publicly Available Date: Oct 25, 2019
• Journal: Neurobiology of Aging
• Print ISSN: 0197-4580
• Electronic ISSN: 1558-1497
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 75
• Pages: 223.e1-223.e10
• DOI: https://doi.org/10.1016/j.neurobiolaging.2018.10.019
• Public URL: https://nottingham-repository.worktribe.com/output/1216046
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S019745801830383X
• Additional Information: This article is maintained by: Elsevier; Article Title: A comprehensive screening of copy number variability in dementia with Lewy bodies; Journal Title: Neurobiology of Aging; CrossRef DOI link to publisher maintained version: https://doi.org/10.1016/j.neurobiolaging.2018.10.019; Content Type: article; Copyright: © 2019 Elsevier Inc. All rights reserved.