The University of Southampton
University of Southampton Institutional Repository

Large-scale assessment of polyglutamine repeat expansions in Parkinson disease

Large-scale assessment of polyglutamine repeat expansions in Parkinson disease
Large-scale assessment of polyglutamine repeat expansions in Parkinson disease
Objectives: We aim to clarify the pathogenic role of intermediate size repeat expansions of SCA2, SCA3, SCA6, and SCA17 as risk factors for idiopathic Parkinson disease (PD).

Methods: We invited researchers from the Genetic Epidemiology of Parkinson's Disease Consortium to participate in the study. There were 12,346 cases and 8,164 controls genotyped, for a total of 4 repeats within the SCA2, SCA3, SCA6, and SCA17 genes. Fixed- and random-effects models were used to estimate the summary risk estimates for the genes. We investigated between-study heterogeneity and heterogeneity between different ethnic populations.

Results: We did not observe any definite pathogenic repeat expansions for SCA2, SCA3, SCA6, and SCA17 genes in patients with idiopathic PD from Caucasian and Asian populations. Furthermore, overall analysis did not reveal any significant association between intermediate repeats and PD. The effect estimates (odds ratio) ranged from 0.93 to 1.01 in the overall cohort for the SCA2, SCA3, SCA6, and SCA17 loci.

Conclusions: Our study did not support a major role for definite pathogenic repeat expansions in SCA2, SCA3, SCA6, and SCA17 genes for idiopathic PD. Thus, results of this large study do not support diagnostic screening of SCA2, SCA3, SCA6, and SCA17 gene repeats in the common idiopathic form of PD. Likewise, this largest multicentered study performed to date excludes the role of intermediate repeats of these genes as a risk factor for PD.
0028-3878
1283-1292
Wang, Lisa
2b3179cf-1d93-4501-b8d4-455e461cc049
Aasly, Jan O.
ba34e0cc-6c06-4c25-b9fe-99e13e6b343f
Annesi, Grazia
fdc98237-0073-4486-8ea3-d39e67d30077
Bardien, Soraya
540bdd32-7e2d-4ae7-926b-4b7d76117cff
Bozi, Maria
9f779e34-aa59-40fd-ac0b-957252f3db1c
Brice, Alexis
6e1e1879-5529-4c89-8b49-be6f5a4395fe
Carr, Jonathan
19791bd4-ea1d-4f5a-a53f-25c35aac6153
Chung, Sun J.
8d6045c1-e485-49e9-b789-b4c8beab7fdc
Clarke, Carl
25a03ef6-9ef6-429c-9180-5cbfa5504660
Crosiers, David
845edd17-d751-4277-8c49-ece0d3766a0f
Deutschländer, Angela
91be39fb-89be-4366-a8fa-d9cc68e7d37d
Eckstein, Gertrud
f922d4b5-2e8a-4cf8-9860-e5e046ac44c7
Farrer, Matthew J.
ac5c58ca-636a-46c7-96d0-7ef36dfe1d57
Goldwurm, Stefano
fce26faf-073d-46e8-a684-288d0ad07f71
Garraux, Gaetan
cc63b379-c680-413a-bf56-8f8d185ceecd
Hadjigeorgiou, Georgios M.
21ab37d2-3556-45c8-aa1e-bb10dcb4f119
Hicks, Andrew A.
b94e286b-b1ec-4a88-b691-e0c30a3d4078
Hattori, Nobutaka
9a587f54-060d-4d79-9984-c596511e7ac7
Klein, Christine
300d3d2d-55da-4c2c-84af-214134e1a424
Jeon, Beom
d7e07278-47a5-4aab-b0e9-670b93953ed0
Kim, Yun J.
c4a426e3-206d-4b0b-a6ee-6aae2bbf611d
Lesage, Suzanne
02db6af5-0012-4b04-bbc9-772e320d6b05
Lin, Juei-Jueng
869a4b86-9c55-4bf1-9a29-6067e27e5a1a
Lynch, Timothy
fc5a3b6d-ef8c-4649-ba3f-f0d5a9fa2844
Lichtner, Peter
5e76ecb9-64a0-408c-ad44-edcbe4a5d50a
Lang, Anthony E.
23b8a8a1-c908-45a8-91e3-6cb1bb713eef
Mok, Vincent
64852e30-79ba-4a07-852f-2c739cdd38e3
Jasinska-Myga, Barbara
fd01b5fb-74ed-48dc-b0b5-404ec5b3939c
Mellick, George D.
81b03925-3ca6-4b5c-8548-9dc575b49293
Morrison, Karen E.
f00890f0-2fde-4dbd-a73b-7422e1b0ede8
Opala, Grzegorz
68d6585a-419c-45c9-973f-0b26adccda06
Pihlstrøm, Lasse
ef3a96f9-8c69-4ed4-84be-cbb0c7e25b95
Pramstaller, Peter P.
bfe5327d-a3df-44ef-b163-258132286079
Park, Sung S.
fa6152df-2019-4c37-891e-5c5123611cd5
Quattrone, Aldo
0d64e33f-2a54-474b-bb28-385be83099c9
Rogaeva, Ekaterina
f9d53d18-eb3d-44d5-add8-dc35f288f6dd
Ross, Owen A.
4df0a0d1-c79d-4465-b4cd-85396219037c
Stefanis, Leonidas
a6f1880a-e589-4ffc-b274-dbc409f3e71d
Stockton, Joanne D.
ba080a47-af64-4752-9ff6-84c0fc8b08e2
Silburn, Peter A.
d8e2000b-3ef5-4916-834a-bdcefb5eebec
Theuns, Jessie
0114b2ca-1ca0-456d-a524-1ae4f064340f
Tan, Eng K.
d6b8cf80-72e4-477e-ab89-26c9cbeb38ab
Tomiyama, Hiroyuki
04ed7369-59de-4ea3-8d68-0d2f705076a7
Toft, Mathias
5d455743-c8f4-466e-bfef-24bc170468fb
Van Broeckhoven, Christine
db56ffb6-a7f9-45d1-9469-3e4cd8153779
Uitti, Ryan J.
aa64b8fa-0f20-4a38-a42e-96e7bb01797d
Wirdefeldt, Karin
14cf4d55-b8bb-4990-aab5-584662347f72
Wszolek, Zbigniew
08e4116b-a032-4d20-9277-0fa2b15a2a9f
Xiromerisiou, Georgia
11d4b090-d901-4f0f-904c-89d898067bc8
Yueh, Kuo-Chu
495a967a-1abf-4aaa-a0a8-69417cf43a6b
Zhao, Yi
158eb3aa-9a01-428f-9cda-663af36d6495
Gasser, Thomas
69ce9799-2571-4a90-a4a9-374418dc3286
Maraganore, Demetrius M.
f5824832-756b-4f0f-a247-9ba64fa180c2
Krüger, Rejko
2799ecf2-513d-43fb-bd37-a48e3694274d
Sharma, Manu
71761491-b70d-4fa9-86fa-e64e73a61290
Wang, Lisa
2b3179cf-1d93-4501-b8d4-455e461cc049
Aasly, Jan O.
ba34e0cc-6c06-4c25-b9fe-99e13e6b343f
Annesi, Grazia
fdc98237-0073-4486-8ea3-d39e67d30077
Bardien, Soraya
540bdd32-7e2d-4ae7-926b-4b7d76117cff
Bozi, Maria
9f779e34-aa59-40fd-ac0b-957252f3db1c
Brice, Alexis
6e1e1879-5529-4c89-8b49-be6f5a4395fe
Carr, Jonathan
19791bd4-ea1d-4f5a-a53f-25c35aac6153
Chung, Sun J.
8d6045c1-e485-49e9-b789-b4c8beab7fdc
Clarke, Carl
25a03ef6-9ef6-429c-9180-5cbfa5504660
Crosiers, David
845edd17-d751-4277-8c49-ece0d3766a0f
Deutschländer, Angela
91be39fb-89be-4366-a8fa-d9cc68e7d37d
Eckstein, Gertrud
f922d4b5-2e8a-4cf8-9860-e5e046ac44c7
Farrer, Matthew J.
ac5c58ca-636a-46c7-96d0-7ef36dfe1d57
Goldwurm, Stefano
fce26faf-073d-46e8-a684-288d0ad07f71
Garraux, Gaetan
cc63b379-c680-413a-bf56-8f8d185ceecd
Hadjigeorgiou, Georgios M.
21ab37d2-3556-45c8-aa1e-bb10dcb4f119
Hicks, Andrew A.
b94e286b-b1ec-4a88-b691-e0c30a3d4078
Hattori, Nobutaka
9a587f54-060d-4d79-9984-c596511e7ac7
Klein, Christine
300d3d2d-55da-4c2c-84af-214134e1a424
Jeon, Beom
d7e07278-47a5-4aab-b0e9-670b93953ed0
Kim, Yun J.
c4a426e3-206d-4b0b-a6ee-6aae2bbf611d
Lesage, Suzanne
02db6af5-0012-4b04-bbc9-772e320d6b05
Lin, Juei-Jueng
869a4b86-9c55-4bf1-9a29-6067e27e5a1a
Lynch, Timothy
fc5a3b6d-ef8c-4649-ba3f-f0d5a9fa2844
Lichtner, Peter
5e76ecb9-64a0-408c-ad44-edcbe4a5d50a
Lang, Anthony E.
23b8a8a1-c908-45a8-91e3-6cb1bb713eef
Mok, Vincent
64852e30-79ba-4a07-852f-2c739cdd38e3
Jasinska-Myga, Barbara
fd01b5fb-74ed-48dc-b0b5-404ec5b3939c
Mellick, George D.
81b03925-3ca6-4b5c-8548-9dc575b49293
Morrison, Karen E.
f00890f0-2fde-4dbd-a73b-7422e1b0ede8
Opala, Grzegorz
68d6585a-419c-45c9-973f-0b26adccda06
Pihlstrøm, Lasse
ef3a96f9-8c69-4ed4-84be-cbb0c7e25b95
Pramstaller, Peter P.
bfe5327d-a3df-44ef-b163-258132286079
Park, Sung S.
fa6152df-2019-4c37-891e-5c5123611cd5
Quattrone, Aldo
0d64e33f-2a54-474b-bb28-385be83099c9
Rogaeva, Ekaterina
f9d53d18-eb3d-44d5-add8-dc35f288f6dd
Ross, Owen A.
4df0a0d1-c79d-4465-b4cd-85396219037c
Stefanis, Leonidas
a6f1880a-e589-4ffc-b274-dbc409f3e71d
Stockton, Joanne D.
ba080a47-af64-4752-9ff6-84c0fc8b08e2
Silburn, Peter A.
d8e2000b-3ef5-4916-834a-bdcefb5eebec
Theuns, Jessie
0114b2ca-1ca0-456d-a524-1ae4f064340f
Tan, Eng K.
d6b8cf80-72e4-477e-ab89-26c9cbeb38ab
Tomiyama, Hiroyuki
04ed7369-59de-4ea3-8d68-0d2f705076a7
Toft, Mathias
5d455743-c8f4-466e-bfef-24bc170468fb
Van Broeckhoven, Christine
db56ffb6-a7f9-45d1-9469-3e4cd8153779
Uitti, Ryan J.
aa64b8fa-0f20-4a38-a42e-96e7bb01797d
Wirdefeldt, Karin
14cf4d55-b8bb-4990-aab5-584662347f72
Wszolek, Zbigniew
08e4116b-a032-4d20-9277-0fa2b15a2a9f
Xiromerisiou, Georgia
11d4b090-d901-4f0f-904c-89d898067bc8
Yueh, Kuo-Chu
495a967a-1abf-4aaa-a0a8-69417cf43a6b
Zhao, Yi
158eb3aa-9a01-428f-9cda-663af36d6495
Gasser, Thomas
69ce9799-2571-4a90-a4a9-374418dc3286
Maraganore, Demetrius M.
f5824832-756b-4f0f-a247-9ba64fa180c2
Krüger, Rejko
2799ecf2-513d-43fb-bd37-a48e3694274d
Sharma, Manu
71761491-b70d-4fa9-86fa-e64e73a61290

Wang, Lisa, Aasly, Jan O., Annesi, Grazia, Bardien, Soraya, Bozi, Maria, Brice, Alexis, Carr, Jonathan, Chung, Sun J., Clarke, Carl, Crosiers, David, Deutschländer, Angela, Eckstein, Gertrud, Farrer, Matthew J., Goldwurm, Stefano, Garraux, Gaetan, Hadjigeorgiou, Georgios M., Hicks, Andrew A., Hattori, Nobutaka, Klein, Christine, Jeon, Beom, Kim, Yun J., Lesage, Suzanne, Lin, Juei-Jueng, Lynch, Timothy, Lichtner, Peter, Lang, Anthony E., Mok, Vincent, Jasinska-Myga, Barbara, Mellick, George D., Morrison, Karen E., Opala, Grzegorz, Pihlstrøm, Lasse, Pramstaller, Peter P., Park, Sung S., Quattrone, Aldo, Rogaeva, Ekaterina, Ross, Owen A., Stefanis, Leonidas, Stockton, Joanne D., Silburn, Peter A., Theuns, Jessie, Tan, Eng K., Tomiyama, Hiroyuki, Toft, Mathias, Van Broeckhoven, Christine, Uitti, Ryan J., Wirdefeldt, Karin, Wszolek, Zbigniew, Xiromerisiou, Georgia, Yueh, Kuo-Chu, Zhao, Yi, Gasser, Thomas, Maraganore, Demetrius M., Krüger, Rejko and Sharma, Manu (2015) Large-scale assessment of polyglutamine repeat expansions in Parkinson disease. Neurology, 85 (15), 1283-1292. (doi:10.1212/WNL.0000000000002016). (PMID:26354989)

Record type: Article

Abstract

Objectives: We aim to clarify the pathogenic role of intermediate size repeat expansions of SCA2, SCA3, SCA6, and SCA17 as risk factors for idiopathic Parkinson disease (PD).

Methods: We invited researchers from the Genetic Epidemiology of Parkinson's Disease Consortium to participate in the study. There were 12,346 cases and 8,164 controls genotyped, for a total of 4 repeats within the SCA2, SCA3, SCA6, and SCA17 genes. Fixed- and random-effects models were used to estimate the summary risk estimates for the genes. We investigated between-study heterogeneity and heterogeneity between different ethnic populations.

Results: We did not observe any definite pathogenic repeat expansions for SCA2, SCA3, SCA6, and SCA17 genes in patients with idiopathic PD from Caucasian and Asian populations. Furthermore, overall analysis did not reveal any significant association between intermediate repeats and PD. The effect estimates (odds ratio) ranged from 0.93 to 1.01 in the overall cohort for the SCA2, SCA3, SCA6, and SCA17 loci.

Conclusions: Our study did not support a major role for definite pathogenic repeat expansions in SCA2, SCA3, SCA6, and SCA17 genes for idiopathic PD. Thus, results of this large study do not support diagnostic screening of SCA2, SCA3, SCA6, and SCA17 gene repeats in the common idiopathic form of PD. Likewise, this largest multicentered study performed to date excludes the role of intermediate repeats of these genes as a risk factor for PD.

Full text not available from this repository.

More information

e-pub ahead of print date: 9 September 2015
Published date: 13 October 2015
Organisations: Medical Education

Identifiers

Local EPrints ID: 398147
URI: http://eprints.soton.ac.uk/id/eprint/398147
ISSN: 0028-3878
PURE UUID: 7a08a05f-c375-4a3e-bcf7-95e80faae926
ORCID for Karen E. Morrison: ORCID iD orcid.org/0000-0003-0216-5717

Catalogue record

Date deposited: 19 Jul 2016 14:08
Last modified: 31 Jul 2019 00:30

Export record

Altmetrics

Contributors

Author: Lisa Wang
Author: Jan O. Aasly
Author: Grazia Annesi
Author: Soraya Bardien
Author: Maria Bozi
Author: Alexis Brice
Author: Jonathan Carr
Author: Sun J. Chung
Author: Carl Clarke
Author: David Crosiers
Author: Angela Deutschländer
Author: Gertrud Eckstein
Author: Matthew J. Farrer
Author: Stefano Goldwurm
Author: Gaetan Garraux
Author: Georgios M. Hadjigeorgiou
Author: Andrew A. Hicks
Author: Nobutaka Hattori
Author: Christine Klein
Author: Beom Jeon
Author: Yun J. Kim
Author: Suzanne Lesage
Author: Juei-Jueng Lin
Author: Timothy Lynch
Author: Peter Lichtner
Author: Anthony E. Lang
Author: Vincent Mok
Author: Barbara Jasinska-Myga
Author: George D. Mellick
Author: Grzegorz Opala
Author: Lasse Pihlstrøm
Author: Peter P. Pramstaller
Author: Sung S. Park
Author: Aldo Quattrone
Author: Ekaterina Rogaeva
Author: Owen A. Ross
Author: Leonidas Stefanis
Author: Joanne D. Stockton
Author: Peter A. Silburn
Author: Jessie Theuns
Author: Eng K. Tan
Author: Hiroyuki Tomiyama
Author: Mathias Toft
Author: Christine Van Broeckhoven
Author: Ryan J. Uitti
Author: Karin Wirdefeldt
Author: Zbigniew Wszolek
Author: Georgia Xiromerisiou
Author: Kuo-Chu Yueh
Author: Yi Zhao
Author: Thomas Gasser
Author: Demetrius M. Maraganore
Author: Rejko Krüger
Author: Manu Sharma

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×