Large-scale assessment of polyglutamine repeat expansions in Parkinson disease

Lisa Wang, Jan O. Aasly, Grazia Annesi, Soraya Bardien, Maria Bozi, Alexis Brice, Jonathan Carr, Sun J. Chung, Carl Clarke, David Crosiers, Angela Deutschländer, Gertrud Eckstein, Matthew J. Farrer, Stefano Goldwurm, Gaetan Garraux, Georgios M. Hadjigeorgiou, Andrew A. Hicks, Nobutaka Hattori, Christine Klein, Beom Jeon & 35 others Yun J. Kim, Suzanne Lesage, Juei Jueng Lin, Timothy Lynch, Peter Lichtner, Anthony E. Lang, Vincent Mok, Barbara Jasinska-Myga, George D. Mellick, Karen E. Morrison, Grzegorz Opala, Lasse PihlstrØm, Peter P. Pramstaller, Sung S. Park, Aldo Quattrone, Ekaterina Rogaeva, Owen A Ross, Leonidas Stefanis, Joanne D. Stockton, Peter A. Silburn, Jessie Theuns, Eng K. Tan, Hiroyuki Tomiyama, Mathias Toft, Christine Van Broeckhoven, Ryan J. Uitti, Karin Wirdefeldt, Zbigniew K Wszolek, Georgia Xiromerisiou, Kuo Chu Yueh, Yi Zhao, Thomas Gasser, Demetrius M. Maraganore, Rejko Krüger, Manu Sharma

Research output: Contribution to journalArticle

13 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1283-1292
Number of pages10
JournalNeurology
Volume85
Issue number15
DOIs
StatePublished - Oct 13 2015

Fingerprint

Parkinson Disease
Genes
Molecular Epidemiology
polyglutamine
Population
Odds Ratio
Research Personnel

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Wang, L., Aasly, J. O., Annesi, G., Bardien, S., Bozi, M., Brice, A., ... Sharma, M. (2015). Large-scale assessment of polyglutamine repeat expansions in Parkinson disease. Neurology, 85(15), 1283-1292. https://doi.org/10.1212/WNL.0000000000002016

Large-scale assessment of polyglutamine repeat expansions in Parkinson disease. / 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 K; Xiromerisiou, Georgia; Yueh, Kuo Chu; Zhao, Yi; Gasser, Thomas; Maraganore, Demetrius M.; Krüger, Rejko; Sharma, Manu.

In: Neurology, Vol. 85, No. 15, 13.10.2015, p. 1283-1292.

Research output: Contribution to journalArticle

Wang, L, Aasly, JO, Annesi, G, Bardien, S, Bozi, M, Brice, A, Carr, J, Chung, SJ, Clarke, C, Crosiers, D, Deutschländer, A, Eckstein, G, Farrer, MJ, Goldwurm, S, Garraux, G, Hadjigeorgiou, GM, Hicks, AA, Hattori, N, Klein, C, Jeon, B, Kim, YJ, Lesage, S, Lin, JJ, Lynch, T, Lichtner, P, Lang, AE, Mok, V, Jasinska-Myga, B, Mellick, GD, Morrison, KE, Opala, G, PihlstrØm, L, Pramstaller, PP, Park, SS, Quattrone, A, Rogaeva, E, Ross, OA, Stefanis, L, Stockton, JD, Silburn, PA, Theuns, J, Tan, EK, Tomiyama, H, Toft, M, Van Broeckhoven, C, Uitti, RJ, Wirdefeldt, K, Wszolek, ZK, Xiromerisiou, G, Yueh, KC, Zhao, Y, Gasser, T, Maraganore, DM, Krüger, R & Sharma, M 2015, 'Large-scale assessment of polyglutamine repeat expansions in Parkinson disease', Neurology, vol. 85, no. 15, pp. 1283-1292. https://doi.org/10.1212/WNL.0000000000002016
Wang L, Aasly JO, Annesi G, Bardien S, Bozi M, Brice A et al. Large-scale assessment of polyglutamine repeat expansions in Parkinson disease. Neurology. 2015 Oct 13;85(15):1283-1292. https://doi.org/10.1212/WNL.0000000000002016
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 K ; Xiromerisiou, Georgia ; Yueh, Kuo Chu ; Zhao, Yi ; Gasser, Thomas ; Maraganore, Demetrius M. ; Krüger, Rejko ; Sharma, Manu. / Large-scale assessment of polyglutamine repeat expansions in Parkinson disease. In: Neurology. 2015 ; Vol. 85, No. 15. pp. 1283-1292.
@article{ff3db17776df4b0f84608764064f17c7,
title = "Large-scale assessment of polyglutamine repeat expansions in Parkinson disease",
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.",
author = "Lisa Wang and Aasly, {Jan O.} and Grazia Annesi and Soraya Bardien and Maria Bozi and Alexis Brice and Jonathan Carr and Chung, {Sun J.} and Carl Clarke and David Crosiers and Angela Deutschl{\"a}nder and Gertrud Eckstein and Farrer, {Matthew J.} and Stefano Goldwurm and Gaetan Garraux and Hadjigeorgiou, {Georgios M.} and Hicks, {Andrew A.} and Nobutaka Hattori and Christine Klein and Beom Jeon and Kim, {Yun J.} and Suzanne Lesage and Lin, {Juei Jueng} and Timothy Lynch and Peter Lichtner and Lang, {Anthony E.} and Vincent Mok and Barbara Jasinska-Myga and Mellick, {George D.} and Morrison, {Karen E.} and Grzegorz Opala and Lasse Pihlstr{\O}m and Pramstaller, {Peter P.} and Park, {Sung S.} and Aldo Quattrone and Ekaterina Rogaeva and Ross, {Owen A} and Leonidas Stefanis and Stockton, {Joanne D.} and Silburn, {Peter A.} and Jessie Theuns and Tan, {Eng K.} and Hiroyuki Tomiyama and Mathias Toft and {Van Broeckhoven}, Christine and Uitti, {Ryan J.} and Karin Wirdefeldt and Wszolek, {Zbigniew K} and Georgia Xiromerisiou and Yueh, {Kuo Chu} and Yi Zhao and Thomas Gasser and Maraganore, {Demetrius M.} and Rejko Kr{\"u}ger and Manu Sharma",
year = "2015",
month = "10",
day = "13",
doi = "10.1212/WNL.0000000000002016",
language = "English (US)",
volume = "85",
pages = "1283--1292",
journal = "Neurology",
issn = "0028-3878",
publisher = "Lippincott Williams and Wilkins",
number = "15",

}

TY - JOUR

T1 - Large-scale assessment of polyglutamine repeat expansions in Parkinson disease

AU - Wang, Lisa

AU - Aasly, Jan O.

AU - Annesi, Grazia

AU - Bardien, Soraya

AU - Bozi, Maria

AU - Brice, Alexis

AU - Carr, Jonathan

AU - Chung, Sun J.

AU - Clarke, Carl

AU - Crosiers, David

AU - Deutschländer, Angela

AU - Eckstein, Gertrud

AU - Farrer, Matthew J.

AU - Goldwurm, Stefano

AU - Garraux, Gaetan

AU - Hadjigeorgiou, Georgios M.

AU - Hicks, Andrew A.

AU - Hattori, Nobutaka

AU - Klein, Christine

AU - Jeon, Beom

AU - Kim, Yun J.

AU - Lesage, Suzanne

AU - Lin, Juei Jueng

AU - Lynch, Timothy

AU - Lichtner, Peter

AU - Lang, Anthony E.

AU - Mok, Vincent

AU - Jasinska-Myga, Barbara

AU - Mellick, George D.

AU - Morrison, Karen E.

AU - Opala, Grzegorz

AU - PihlstrØm, Lasse

AU - Pramstaller, Peter P.

AU - Park, Sung S.

AU - Quattrone, Aldo

AU - Rogaeva, Ekaterina

AU - Ross, Owen A

AU - Stefanis, Leonidas

AU - Stockton, Joanne D.

AU - Silburn, Peter A.

AU - Theuns, Jessie

AU - Tan, Eng K.

AU - Tomiyama, Hiroyuki

AU - Toft, Mathias

AU - Van Broeckhoven, Christine

AU - Uitti, Ryan J.

AU - Wirdefeldt, Karin

AU - Wszolek, Zbigniew K

AU - Xiromerisiou, Georgia

AU - Yueh, Kuo Chu

AU - Zhao, Yi

AU - Gasser, Thomas

AU - Maraganore, Demetrius M.

AU - Krüger, Rejko

AU - Sharma, Manu

PY - 2015/10/13

Y1 - 2015/10/13

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84944415009&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84944415009&partnerID=8YFLogxK

U2 - 10.1212/WNL.0000000000002016

DO - 10.1212/WNL.0000000000002016

M3 - Article

VL - 85

SP - 1283

EP - 1292

JO - Neurology

JF - Neurology

SN - 0028-3878

IS - 15

ER -