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; 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 Wszolek; Georgia Xiromerisiou; Kuo Chu Yueh; Yi Zhao; Thomas Gasser; Demetrius M. Maraganore; Rejko Krüger; Manu Sharma

doi:10.1212/WNL.0000000000002016

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 JeonYun 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 Wszolek, Georgia Xiromerisiou, Kuo Chu Yueh, Yi Zhao, Thomas Gasser, Demetrius M. Maraganore, Rejko Krüger, Manu Sharma

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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 language	English (US)
Pages (from-to)	1283-1292
Number of pages	10
Journal	Neurology
Volume	85
Issue number	15
DOIs	https://doi.org/10.1212/WNL.0000000000002016
State	Published - Oct 13 2015

ASJC Scopus subject areas

Clinical Neurology

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10.1212/WNL.0000000000002016

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Wang, L., Aasly, J. O., Annesi, G., Bardien, S., Bozi, M., Brice, A., Carr, J., Chung, S. J., Clarke, C., Crosiers, D., Deutschländer, A., Eckstein, G., Farrer, M. J., Goldwurm, S., Garraux, G., Hadjigeorgiou, G. M., Hicks, A. A., Hattori, N., Klein, C., ... 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

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, Z, 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

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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 Zbigniew Wszolek 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",

note = "Publisher Copyright: {\textcopyright} 2015 American Academy of Neurology.",

year = "2015",

month = oct,

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",

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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

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.

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Large-scale assessment of polyglutamine repeat expansions in Parkinson disease

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