Advanced

Genetic analysis implicates APOE, SNCA and suggests lysosomal dysfunction in the etiology of Dementia with Lewy Bodies.

Bras, Jose; Guerreiro, Rita; Darwent, Lee; Parkkinen, Laura; Ansorge, Olaf; Escott-Price, Valentina; Hernandez, Dena G; Nalls, Michael A; Clark, Lorraine and Honig, Lawrence, et al. (2014) In Human Molecular Genetics 23(23). p.6139-6146
Abstract
Clinical and neuropathological similarities between Dementia with Lewy Bodies (DLB), ParkinsonÕs and AlzheimerÕs diseases (PD and AD, respectively) suggest that these disorders may share etiology. To test this hypothesis we have performed an association study of 54 genomic regions, previously implicated in PD or AD, in a large cohort of DLB cases and controls. The cohort comprised 788 DLB cases and 2624 controls. To minimize the issue of potential misdiagnosis, we have also performed the analysis including only neuropathologically proven DLB cases (667 cases). Results show that the APOE is a strong genetic risk factor for DLB, confirming previous findings, and that the SNCA and SCARB2 loci are also associated after study-wise Bonferroni... (More)
Clinical and neuropathological similarities between Dementia with Lewy Bodies (DLB), ParkinsonÕs and AlzheimerÕs diseases (PD and AD, respectively) suggest that these disorders may share etiology. To test this hypothesis we have performed an association study of 54 genomic regions, previously implicated in PD or AD, in a large cohort of DLB cases and controls. The cohort comprised 788 DLB cases and 2624 controls. To minimize the issue of potential misdiagnosis, we have also performed the analysis including only neuropathologically proven DLB cases (667 cases). Results show that the APOE is a strong genetic risk factor for DLB, confirming previous findings, and that the SNCA and SCARB2 loci are also associated after study-wise Bonferroni correction, although these have a different association profile than the associations reported for the same loci in PD. We have previously shown that the p.N370S variant in GBA is associated with DLB, which, together with the findings at the SCARB2 locus, suggests a role for lysosomal dysfunction in this disease. These results indicate that DLB has a unique genetic risk profile when compared to the two most common neurodegenerative diseases and that the lysosome may play an important role in the etiology of this disorder. We make all these data available. (Less)
Please use this url to cite or link to this publication:
author
, et al. (More)
(Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Human Molecular Genetics
volume
23
issue
23
pages
6139 - 6146
publisher
Oxford University Press
external identifiers
  • pmid:24973356
  • wos:000346777400001
  • scopus:84908296281
ISSN
0964-6906
DOI
10.1093/hmg/ddu334
language
English
LU publication?
yes
id
0368d600-7e27-4d26-95e8-35d4379ea189 (old id 4523673)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/24973356?dopt=Abstract
date added to LUP
2014-07-08 11:37:39
date last changed
2017-11-12 03:05:24
@article{0368d600-7e27-4d26-95e8-35d4379ea189,
  abstract     = {Clinical and neuropathological similarities between Dementia with Lewy Bodies (DLB), ParkinsonÕs and AlzheimerÕs diseases (PD and AD, respectively) suggest that these disorders may share etiology. To test this hypothesis we have performed an association study of 54 genomic regions, previously implicated in PD or AD, in a large cohort of DLB cases and controls. The cohort comprised 788 DLB cases and 2624 controls. To minimize the issue of potential misdiagnosis, we have also performed the analysis including only neuropathologically proven DLB cases (667 cases). Results show that the APOE is a strong genetic risk factor for DLB, confirming previous findings, and that the SNCA and SCARB2 loci are also associated after study-wise Bonferroni correction, although these have a different association profile than the associations reported for the same loci in PD. We have previously shown that the p.N370S variant in GBA is associated with DLB, which, together with the findings at the SCARB2 locus, suggests a role for lysosomal dysfunction in this disease. These results indicate that DLB has a unique genetic risk profile when compared to the two most common neurodegenerative diseases and that the lysosome may play an important role in the etiology of this disorder. We make all these data available.},
  author       = {Bras, Jose and Guerreiro, Rita and Darwent, Lee and Parkkinen, Laura and Ansorge, Olaf and Escott-Price, Valentina and Hernandez, Dena G and Nalls, Michael A and Clark, Lorraine and Honig, Lawrence and Marder, Karen and van der Flier, Wiesje and Lemstra, Afina and Scheltens, Philip and Rogaeva, Ekaterina and St George-Hyslop, Peter and Londos, Elisabet and Zetterberg, Henrik and Ortega-Cubero, Sara and Pastor, Pau and Ferman, Tanis J and Graff-Radford, Neill R and Ross, Owen A and Barber, Imelda and Braae, Anne and Brown, Kristelle and Morgan, Kevin and Maetzler, Walter and Berg, Daniela and Troakes, Claire and Al-Sarraj, Safa and Lashley, Tammaryn and Compta, Yarko and Revesz, Tamas and Lees, Andrew and Cairns, Nigel and Halliday, Glenda M and Mann, David and Pickering-Brown, Stuart and Dickson, Dennis and Singleton, Andrew and Hardy, John},
  issn         = {0964-6906},
  language     = {eng},
  number       = {23},
  pages        = {6139--6146},
  publisher    = {Oxford University Press},
  series       = {Human Molecular Genetics},
  title        = {Genetic analysis implicates APOE, SNCA and suggests lysosomal dysfunction in the etiology of Dementia with Lewy Bodies.},
  url          = {http://dx.doi.org/10.1093/hmg/ddu334},
  volume       = {23},
  year         = {2014},
}