Journal Article

DZNE-2020-06767

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png A comprehensive screening of copy number variability in dementia with Lewy bodies.

Kun-Rodrigues, C. ; Orme, T. ; Carmona, S. ; Hernandez, D. G.DZNE* ; Ross, O. A. ; Eicher, J. D. ; Shepherd, C. ; Parkkinen, L. ; Darwent, L. ; Heckman, M. G. ; Scholz, S. W. ; Troncoso, J. C. ; Pletnikova, O. ; Dawson, T. ; Rosenthal, L. ; Ansorge, O. ; Clarimon, J. ; Lleo, A. ; Morenas-Rodriguez, E. ; Clark, L. ; Honig, L. S. ; 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, G. E. ; Beach, T. G. ; Lesage, S. ; Galasko, D. ; Masliah, E. ; Santana, I. ; Pastor, P. ; Diez-Fairen, M. ; Aguilar, M. ; Tienari, P. J. ; Myllykangas, L. ; Oinas, M. ; Revesz, T. ; Lees, A. ; Boeve, B. F. ; Petersen, R. C. ; Ferman, T. J. ; Escott-Price, V. ; Graff-Radford, N. ; Cairns, N. J. ; Morris, J. C. ; Pickering-Brown, S. ; Mann, D. ; Halliday, G. M. ; Hardy, J. ; Trojanowski, J. Q. ; Dickson, D. W. ; Singleton, A. ; Stone, D. J. ; Guerreiro, R. ; Bras, J. (Corresponding author)

2019
Elsevier Science Amsterdam [u.a.]

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Please use a persistent id in citations: doi:10.1016/j.neurobiolaging.2018.10.019

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.

Keyword(s): Adaptor Proteins, Signal Transducing: genetics (MeSH) ; Aged, 80 and over (MeSH) ; DNA Copy Number Variations: genetics (MeSH) ; Female (MeSH) ; Genetic Predisposition to Disease: genetics (MeSH) ; Genome (MeSH) ; Genome-Wide Association Study (MeSH) ; Humans (MeSH) ; Lewy Body Disease: genetics (MeSH) ; Male (MeSH) ; Membrane Proteins: genetics (MeSH) ; Oncogene Proteins: genetics (MeSH) ; Polymorphism, Single Nucleotide: genetics (MeSH) ; Adaptor Proteins, Signal Transducing ; Membrane Proteins ; Oncogene Proteins

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Contributing Institute(s):

1. Genome Biology of Neurodegenerative Diseases (AG Heutink)

Research Program(s):

1. 345 - Population Studies and Genetics (POF3-345) (POF3-345)

Appears in the scientific report 2019

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Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF >= 5 ; JCR ; Nationallizenz ; SCOPUS ; Web of Science Core Collection

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