| Literature DB >> 30448004 |
Celia Kun-Rodrigues1, Tatiana Orme2, Susana Carmona2, Dena G Hernandez3, Owen A Ross4, John D Eicher5, Claire Shepherd6, Laura Parkkinen7, Lee Darwent8, Michael G Heckman9, Sonja W Scholz10, Juan C Troncoso11, Olga Pletnikova11, Ted Dawson12, Liana Rosenthal12, Olaf Ansorge7, Jordi Clarimon13, Alberto Lleo13, Estrella Morenas-Rodriguez13, Lorraine Clark14, Lawrence S Honig14, Karen Marder14, Afina Lemstra15, Ekaterina Rogaeva16, Peter St George-Hyslop17, Elisabet Londos18, Henrik Zetterberg19, Imelda Barber20, Anne Braae20, Kristelle Brown20, Kevin Morgan20, Claire Troakes21, Safa Al-Sarraj21, Tammaryn Lashley22, Janice Holton22, Yaroslau Compta23, Vivianna Van Deerlin24, Geidy E Serrano25, Thomas G Beach25, Suzanne Lesage26, Douglas Galasko27, Eliezer Masliah28, Isabel Santana29, Pau Pastor30, Monica Diez-Fairen30, Miquel Aguilar30, Pentti J Tienari31, Liisa Myllykangas32, Minna Oinas33, Tamas Revesz22, Andrew Lees22, Brad F Boeve34, Ronald C Petersen34, Tanis J Ferman35, Valentina Escott-Price36, Neill Graff-Radford37, Nigel J Cairns38, John C Morris38, Stuart Pickering-Brown39, David Mann39, Glenda M Halliday40, John Hardy1, John Q Trojanowski24, Dennis W Dickson4, Andrew Singleton41, David J Stone42, Rita Guerreiro43, Jose Bras44.
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.Entities:
Keywords: Copy number variants; Dementia with Lewy bodies; Genome-wide; MAPT; SNCA
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Year: 2018 PMID： 30448004 PMCID： PMC6541211 DOI： 10.1016/j.neurobiolaging.2018.10.019
Source DB: PubMed Journal: Neurobiol Aging ISSN： 0197-4580 Impact factor: 4.673