A comprehensive screening of copy number variability in dementia with Lewy bodies
| Autor: | Sonja W. Scholz, Pentti J. Tienari, Dena G. Hernandez, Elisabet Londos, Alberto Lleó, Imelda Barber, Jose Bras, Owen A. Ross, Tanis J. Ferman, Tatiana Orme, Juan C. Troncoso, Andrew B. Singleton, John D. Eicher, John Hardy, Karen Marder, Tammaryn Lashley, Douglas Galasko, Liisa Myllykangas, Ted M. Dawson, Eliezer Masliah, David M. A. Mann, Ekaterina Rogaeva, Stuart Pickering-Brown, Monica Diez-Fairen, Claire Troakes, Peter St George-Hyslop, Nigel J. Cairns, Dennis W. Dickson, Lee Darwent, Thomas G. Beach, David J. Stone, Olga Pletnikova, Glenda M. Halliday, Jordi Clarimón, John Q. Trojanowski, Anne Braae, Claire E. Shepherd, Pau Pastor, Geidy E. Serrano, Susana Carmona, Minna Oinas, Andrew J. Lees, Afina W. Lemstra, Miquel Aguilar, Laura Parkkinen, Rita Guerreiro, Estrella Morenas-Rodríguez, Janice L. Holton, Olaf Ansorge, Tamas Revesz, Vivianna M. Van Deerlin, Neill R. Graff-Radford, Safa Al-Sarraj, Kristelle Brown, Valentina Escott-Price, Suzanne Lesage, Lawrence S. Honig, Celia Kun-Rodrigues, John C. Morris, Ronald C. Petersen, Henrik Zetterberg, Kevin Morgan, Brad F. Boeve, Lorraine N. Clark, Isabel Santana, Yaroslau Compta, Liana S. Rosenthal, Michael G. Heckman |
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| Přispěvatelé: | Neurology, Amsterdam Neuroscience - Neurodegeneration, Department of Neurosciences, Research Programme for Molecular Neurology, Pentti Tienari / Principal Investigator, Neurologian yksikkö, Research Programs Unit, Clinicum, Department of Pathology, Liisa Tellervo Myllykangas / Principal Investigator, Medicum, Neurokirurgian yksikkö, HUS Neurocenter |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Aging Candidate gene ALPHA-SYNUCLEIN Dementia with Lewy bodies Genome-wide association study Variações do Número de Cópias de DNA 3124 Neurology and psychiatry 0302 clinical medicine RARE genetics [Lewy Body Disease] genetics [Adaptor Proteins Signal Transducing] PURINE METABOLISM MAPT GENE MAPT GLUCOCEREBROSIDASE MUTATIONS Genome-wide Copy-number variation genetics [Genetic Predisposition to Disease] SNAPSHOT GENETICS SYNUCLEIN GENE DUPLICATION Aged 80 and over Oncogene Proteins Genome General Neuroscience 3. Good health ALZHEIMERS-DISEASE genetics [Membrane Proteins] genetics [Polymorphism Single Nucleotide] Medical genetics Female Lewy Body Disease medicine.medical_specialty Doença por Corpos de Lewy DNA Copy Number Variations genetics [DNA Copy Number Variations] Computational biology Biology Polymorphism Single Nucleotide behavioral disciplines and activities Article 03 medical and health sciences mental disorders medicine Humans Genetic Predisposition to Disease ddc:610 Genetic variability GENOME-WIDE ASSOCIATION Genotyping PARKINSON-DISEASE Genetic association Adaptor Proteins Signal Transducing Copy number variants Membrane Proteins genetics [Oncogene Proteins] medicine.disease nervous system diseases Proteínas Oncogénicas 030104 developmental biology SNCA Neurology (clinical) Geriatrics and Gerontology Predisposição Genética para Doença 030217 neurology & neurosurgery Developmental Biology Genome-Wide Association Study |
| Zdroj: | Kun-Rodrigues, C, Orme, T, Carmona, S, Hernandez, D G, 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 2019, ' A comprehensive screening of copy number variability in dementia with Lewy bodies ', Neurobiology of Aging, vol. 75, pp. 223.e1-223.e10 . https://doi.org/10.1016/j.neurobiolaging.2018.10.019 Neurobiology of aging 75, 223.e1-223.e10 (2019). doi:10.1016/j.neurobiolaging.2018.10.019 Neurobiology of Aging, 75, 223.e1-223.e10. Elsevier Inc. NEUROBIOLOGY OF AGING r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau instname |
| ISSN: | 0197-4580 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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