A comprehensive screening of copy number variability in dementia with Lewy bodies
Celia Kun-Rodrigues
(1, 2)
,
Tatiana Orme
(1, 2)
,
Susana Carmona
(1, 2)
,
Dena Hernandez
,
Owen Ross
(3)
,
John Eicher
(4)
,
Claire Shepherd
(5, 6)
,
Laura Parkkinen
(7)
,
Lee Darwent
(2)
,
Michael Heckman
(3)
,
Sonja Scholz
(8, 9)
,
Juan Troncoso
(9)
,
Olga Pletnikova
(9)
,
Ted Dawson
(9)
,
Liana Rosenthal
(9)
,
Olaf Ansorge
(7)
,
Jordi Clarimon
(10, 11)
,
Alberto Lleo
(10, 11)
,
Estrella Morenas-Rodriguez
(10, 11)
,
Lorraine Clark
(12)
,
Lawrence Honig
(12)
,
Karen Marder
(12)
,
Afina Lemstra
(13)
,
Ekaterina Rogaeva
(14, 15)
,
Peter St George-Hyslop
(14, 15)
,
Elisabet Londos
(16)
,
Henrik Zetterberg
(2, 17)
,
Imelda Barber
(18)
,
Anne Braae
(18)
,
Kristelle Brown
(18)
,
Kevin Morgan
(18)
,
Claire Troakes
(19)
,
Safa Al-Sarraj
(19)
,
Tammaryn Lashley
(1)
,
Janice Holton
(1)
,
Yaroslau Compta
(1)
,
Vivianna van Deerlin
(20)
,
Geidy Serrano
,
Thomas Beach
,
Suzanne Lesage
(21)
,
Douglas Galasko
(22)
,
Eliezer Masliah
(22)
,
Isabel Santana
,
Pau Pastor
(23)
,
Monica Diez-Fairen
(23)
,
Miquel Aguilar
(23)
,
Pentti Tienari
(24)
,
Liisa Myllykangas
(25, 24)
,
Minna Oinas
(25, 24)
,
Tamas Revesz
(1)
,
Andrew Lees
(1)
,
Brad Boeve
(26)
,
Ronald Petersen
(26)
,
Tanis Ferman
(3)
,
Valentina Escott-Price
(27)
,
Neill Graff-Radford
(3)
,
Nigel Cairns
(28)
,
John Morris
(28)
,
Stuart Pickering-Brown
(29)
,
David Mann
(29)
,
Glenda Halliday
(6, 5)
,
John Hardy
(1)
,
John Trojanowski
(20)
,
Dennis Dickson
(3)
,
Andrew Singleton
,
David Stone
(4)
,
Rita Guerreiro
(2)
,
Jose Bras
(1, 2)
1
UCL Queen Square Institute of Neurology
2 UK DRI - UK Dementia Research Institute
3 Mayo Clinic [Jacksonville]
4 Merck Research Laboratories
5 NeuRA - Neuroscience Research Australia
6 UNSW - University of New South Wales [Sydney]
7 Nuffield Department of Clinical Neurosciences [Oxford]
8 NINDS - National Institute of Neurological Disorders and Stroke [Bethesda]
9 Johns Hopkins University School of Medicine [Baltimore]
10 Hospital de la Santa Creu i Sant Pau
11 CIBERNED - Centro de Investigacion Biomédica en Red sobre Enfermedades Neurodegenerativas
12 Columbia University [New York]
13 VU University Medical Center [Amsterdam]
14 Tanz Center Research in Neurodegenerative Diseases [Toronto]
15 University of Toronto
16 Lund University
17 Institute of Neuroscience and Physiology [Göteborg]
18 School of Life Sciences
19 King‘s College London
20 Perelman School of Medicine
21 ICM - Institut du Cerveau = Paris Brain Institute
22 UC San Diego - University of California [San Diego]
23 Hospital Universitario Mutua de Terrassa
24 Helsingin yliopisto = Helsingfors universitet = University of Helsinki
25 HUS - Helsinki University Hospital [Finland]
26 Mayo Clinic [Rochester]
27 Cardiff University
28 Washington University School of Medicine in St. Louis
29 University of Manchester [Manchester]
2 UK DRI - UK Dementia Research Institute
3 Mayo Clinic [Jacksonville]
4 Merck Research Laboratories
5 NeuRA - Neuroscience Research Australia
6 UNSW - University of New South Wales [Sydney]
7 Nuffield Department of Clinical Neurosciences [Oxford]
8 NINDS - National Institute of Neurological Disorders and Stroke [Bethesda]
9 Johns Hopkins University School of Medicine [Baltimore]
10 Hospital de la Santa Creu i Sant Pau
11 CIBERNED - Centro de Investigacion Biomédica en Red sobre Enfermedades Neurodegenerativas
12 Columbia University [New York]
13 VU University Medical Center [Amsterdam]
14 Tanz Center Research in Neurodegenerative Diseases [Toronto]
15 University of Toronto
16 Lund University
17 Institute of Neuroscience and Physiology [Göteborg]
18 School of Life Sciences
19 King‘s College London
20 Perelman School of Medicine
21 ICM - Institut du Cerveau = Paris Brain Institute
22 UC San Diego - University of California [San Diego]
23 Hospital Universitario Mutua de Terrassa
24 Helsingin yliopisto = Helsingfors universitet = University of Helsinki
25 HUS - Helsinki University Hospital [Finland]
26 Mayo Clinic [Rochester]
27 Cardiff University
28 Washington University School of Medicine in St. Louis
29 University of Manchester [Manchester]
Susana Carmona
- Fonction : Auteur
- PersonId : 1377657
- ORCID : 0000-0002-9522-7771
Dena Hernandez
- Fonction : Auteur
Claire Shepherd
- Fonction : Auteur
- PersonId : 1377658
- ORCID : 0000-0002-0399-3218
Sonja Scholz
- Fonction : Auteur
- PersonId : 1275782
- ORCID : 0000-0002-6623-0429
Tammaryn Lashley
- Fonction : Auteur
- PersonId : 1354359
- ORCID : 0000-0001-7389-0348
Vivianna van Deerlin
- Fonction : Auteur
- PersonId : 1215607
- ORCID : 0000-0002-7400-9097
Geidy Serrano
- Fonction : Auteur
Thomas Beach
- Fonction : Auteur
Isabel Santana
- Fonction : Auteur
Pau Pastor
- Fonction : Auteur
- PersonId : 1377660
- ORCID : 0000-0002-2573-6378
Valentina Escott-Price
- Fonction : Auteur
- PersonId : 1305604
- ORCID : 0000-0003-1784-5483
Dennis Dickson
- Fonction : Auteur
- PersonId : 1144849
- ORCID : 0000-0001-7189-7917
- IdRef : 090949390
Andrew Singleton
- Fonction : Auteur
Rita Guerreiro
- Fonction : Auteur
- PersonId : 1377661
- ORCID : 0000-0001-5879-3486
Jose Bras
- Fonction : Auteur
- PersonId : 1359609
- ORCID : 0000-0001-8186-0333
Résumé
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.