Genetic Risk Factors in Isolated Dystonia Escape Genome-Wide Association Studies

被引：2

作者：

Laabs, Bjoern-Hergen ^{[1
]}

Lohmann, Katja ^{[2
]}

Vollstedt, Eva-Juliane ^{[2
]}

Reinberger, Tobias ^{[3
]}

Nuxoll, Lisa-Marie ^{[1
]}

Kilic-Berkmen, Gamze ^{[4
]}

Perlmutter, Joel S. ^{[5
]}

Loens, Sebastian ^{[6
]}

Cruchaga, Carlos ^{[7
]}

Franke, Andre ^{[8
]}

Dobricic, Valerija ^{[9
]}

Hinrichs, Frauke ^{[2
]}

Groezinger, Anne ^{[2
]}

Altenmueller, Eckart ^{[10
]}

Bellows, Steven ^{[11
]}

Boesch, Sylvia ^{[12
]}

Bressman, Susan B. ^{[13
,14
]}

Duque, Kevin R. ^{[15
]}

Espay, Alberto J. ^{[15
]}

Ferbert, Andreas ^{[16
]}

Feuerstein, Jeanne S. ^{[17
]}

Frank, Samuel ^{[18
]}

Gasser, Thomas ^{[19
,20
,21
]}

Haslinger, Bernhard ^{[22
]}

Jech, Robert ^{[23
,24
]}

Kaiser, Frank ^{[25
,26
]}

Kamm, Christoph ^{[27
]}

Kollewe, Katja ^{[28
]}

Kuehn, Andrea A. ^{[29
]}

LeDoux, Mark S. ^{[30
,31
]}

Lohmann, Ebba ^{[19
,20
,21
]}

Mahajan, Abhimanyu ^{[32
]}

Muenchau, Alexander ^{[6
]}

Multhaupt-Buell, Trisha ^{[33
,34
]}

Pantelyat, Alexander ^{[35
]}

Richardson, Sarah E. Pirio ^{[36
]}

Raymond, Deborah ^{[13
]}

Reich, Stephen G. ^{[37
]}

Saunders Pullman, Rachel ^{[13
,14
]}

Schormair, Barbara ^{[38
,39
]}

Sharma, Nutan ^{[33
,34
]}

Sichani, Azadeh Hamzehei ^{[14
,40
,41
]}

Simonyan, Kristina ^{[14
,32
,33
,34
,40
,41
]}

Volkmann, Jens ^{[42
]}

Shukla, Aparna Wagle ^{[43
]}

Winkelmann, Juliane ^{[38
,39
,44
]}

Wright, Laura J. ^{[45
]}

Zech, Michael ^{[38
,39
]}

Zeuner, Kirsten E. ^{[46
]}

Zittel, Simone ^{[47
]}

机构：

[1] Univ Lubeck, Inst Med Biometry & Stat, Ratzeburger Allee 160, D-23538 Lubeck, Germany

[2] Univ Lubeck, Inst Neurogenet, Ratzeburger Allee 160, D-23538 Lubeck, Germany

[3] Univ Lubeck, Inst Cardiogenet, Lubeck, Germany

[4] Emory Univ, Dept Neurol, Atlanta, GA USA

[5] Washington Univ, Sch Med, Dept Neurol Radiol & Neurosci, St Louis, MO USA

[6] Univ Lubeck, Inst Syst Motor Sci, CBBM, Lubeck, Germany

[7] Washington Univ, Dept Psychiat, Sch Med, St Louis, MO USA

[8] Univ Kiel, Inst Clin Mol Biol, Kiel, Germany

[9] Univ Lubeck, Lubeck Interdisciplinary Platform Genome Anal, Lubeck, Germany

[10] Hanover Univ Mus Drama & Media, Inst Mus Physiol & Musicians Med, Hannover, NH, Germany

[11] Baylor Coll Med, Parkinsons Dis Ctr & Movement Disorder Clin, Houston, TX USA

[12] Med Univ Innsbruck, Dept Neurol, Innsbruck, Austria

[13] Mt Sinai Beth Israel Med Ctr, Dept Neurol, New York, NY USA

[14] Icahn Sch Med Mt Sinai, Dept Neurol, New York, NY USA

[15] Univ Cincinnati, Coll Med, James J & Joan Gardner Family Ctr Parkinsons Dis, Cincinnati, OH USA

[16] Klinikum Kassel, Kassel Sch Med, Dept Neurol, Kassel, Germany

[17] Univ Colorado, Sch Med, Dept Neurol, Aurora, CO USA

[18] Harvard Med Sch, Dept Neurol, Beth Israel Deaconess Med Ctr, Boston, MA USA

[19] Univ Tubingen, Dept Neurol, Tubingen, Germany

[20] Univ Tubingen, Hertie Inst Clin Brain Res, Tubingen, Germany

[21] Univ Tubingen, DZNE, Tubingen, Germany

[22] Tech Univ Munich, Sch Med, Dept Neurol, Klinikum Rechts Isar, Munich, Germany

[23] Charles Univ Prague, Fac Med 1, Dept Neurol, Prague, Czech Republic

[24] Gen Univ Hosp Prague, Prague, Czech Republic

[25] Univ Duisburg Essen, Univ Hosp Essen, Inst Human Genet, Essen, Germany

[26] Univ Hosp Essen, Essener Zentrum Seltene Erkrankungen, Essen, Germany

[27] Univ Med Ctr Rostock, Dept Neurol, Rostock, Germany

[28] Hannover Med Sch, Neurol Clin, Hannover, Germany

[29] Charite, Dept Neurol & Expt Neurol, Berlin, Germany

[30] Verac Neurosci LLC, Memphis, TN USA

[31] Univ Memphis, Dept Psychol, Memphis, TN USA

[32] Rush Univ, Dept Neurol Sci, Chicago, IL USA

[33] Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA

[34] Harvard Med Sch, Boston, MA USA

[35] Johns Hopkins Med, Dept Neurol, Baltimore, MD USA

[36] Univ New Mexico, Dept Neurol, Albuquerque, NM USA

[37] Univ Maryland, Sch Med, Baltimore, MD USA

[38] Helmholtz Zentrum Munchen, Inst Neurogenom, Munich, Germany

[39] Tech Univ Munich, Inst Human Genet, Sch Med, Munich, Germany

[40] Massachusetts Eye & Ear, Dept Otolaryngol Head & Neck Surg, Boston, MA USA

[41] Harvard Med Sch, Boston, MA USA

[42] Univ Hosp Wurzburg, Dept Neurol, Wurzburg, Germany

[43] Univ Florida, Dept Neurol, Gainesville, FL USA

[44] Munich Cluster Syst Neurol, SyNergy, Munich, Germany

[45] Washington Univ, Dept Neurol, Sch Med, St Louis, MO USA

[46] Univ Kiel, Neurol Clin, Kiel, Germany

[47] Univ Med Ctr Hamburg Eppendorf, Dept Neurol, Hamburg, Germany

[48] Univ Lubeck, Dept Psychiat & Psychotherapy, Lubeck, Germany

[49] Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA USA

[50] Univ Lubeck, Dept Neurol, Lubeck, Germany

来源：

MOVEMENT DISORDERS | 2024年 / 39卷 / 11期

基金：

美国国家卫生研究院;

关键词：

isolated dystonia; GWAS; age at onset; clinical score; case-control; MUSICIANS DYSTONIA; MUTATIONS; ONSET;

D O I：

10.1002/mds.29968

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Background: Despite considerable heritability, previous smaller genome-wide association studies (GWASs) have not identified any robust genetic risk factors for isolated dystonia. Objective: The objective of this study was to perform a large-scale GWAS in a well-characterized, multicenter sample of >6000 individuals to identify genetic risk factors for isolated dystonia. Methods: Array-based GWASs were performed on autosomes for 4303 dystonia participants and 2362 healthy control subjects of European ancestry with subgroup analysis based on age at onset, affected body regions, and a newly developed clinical score. Another 736 individuals were used for validation. Results: This GWAS identified no common genome-wide significant loci that could be replicated despite sufficient power to detect meaningful effects. Power analyses imply that the effects of individual variants are likely very small. Conclusions: Moderate single-nucleotide polymorphism-based heritability indicates that common variants do not contribute to isolated dystonia in this cohort. Sequence-based GWASs (eg, by whole-genome sequencing) might help to better understand the genetic basis. (c) 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

引用

页码：2110 / 2116

页数：7

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