孤立性肌张力障碍的遗传风险因素全基因组关联研究

IF 7.4 1区医学 Q1 CLINICAL NEUROLOGY Movement Disorders Pub Date : 2024-09-17 DOI:10.1002/mds.29968

Björn-Hergen Laabs PhD, Katja Lohmann PhD, Eva-Juliane Vollstedt MD, Tobias Reinberger PhD, Lisa-Marie Nuxoll MSc, Gamze Kilic-Berkmen PhD, Joel S. Perlmutter MD, Sebastian Loens MD, Carlos Cruchaga PhD, Andre Franke PhD, Valerija Dobricic PhD, Frauke Hinrichs, Anne Grözinger BSc, Eckart Altenmüller MD, Steven Bellows MD, Sylvia Boesch MD, MSc, Susan B. Bressman MD, Kevin R. Duque MD, Alberto J. Espay MD, Andreas Ferbert MD, Jeanne S. Feuerstein MD, Samuel Frank MD, Thomas Gasser MD, Bernhard Haslinger MD, Robert Jech MD, PhD, Frank Kaiser PhD, Christoph Kamm MD, Katja Kollewe MD, Andrea A. Kühn MD, Mark S. LeDoux MD, PhD, Ebba Lohmann MD, Abhimanyu Mahajan MD, MHS, Alexander Münchau MD, Trisha Multhaupt-Buell MS, CGC, Alexander Pantelyat MD, Sarah E. Pirio Richardson MD, Deborah Raymond MS, CGC, Stephen G. Reich MD, Rachel Saunders Pullman MD, MPH, MSc, Barbara Schormair PhD, Nutan Sharma MD, PhD, Azadeh Hamzehei Sichani MA, Kristina Simonyan MD, PhD, DrMed, Jens Volkmann MD, Aparna Wagle Shukla MD, Juliane Winkelmann MD, Laura J. Wright MA, Michael Zech MD, Kirsten E. Zeuner MD, Simone Zittel MD, Meike Kasten MD, Yan V. Sun PhD, Tobias Bäumer MD, Norbert Brüggemann MD, Laurie J. Ozelius PhD, Hyder A. Jinnah MD, PhD, Christine Klein MD, Inke R. König PhD

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引用次数: 0

摘要

背景尽管具有相当大的遗传性，但之前的小型全基因组关联研究（GWAS）并未发现孤立性肌张力障碍的任何强有力的遗传风险因素。目的本研究的目的是在一个特征明确的、多中心的>6000人样本中进行大规模的GWAS，以确定孤立性肌张力障碍的遗传风险因素。方法对 4303 名肌张力障碍患者和 2362 名欧洲血统健康对照受试者的常染色体进行了基于芯片的 GWAS，并根据发病年龄、受影响的身体区域和新开发的临床评分进行了亚组分析。结果这项全球基因组研究没有发现可重复的全基因组显著位点，尽管有足够的力量检测有意义的效应。结论基于单核苷酸多态性的适度遗传性表明，常见变异不会导致该队列中的孤立性肌张力障碍。基于序列的全球基因组研究（如全基因组测序）可能有助于更好地了解其遗传基础。© 2024 The Author(s).运动障碍》由 Wiley Periodicals LLC 代表国际帕金森和运动障碍协会出版。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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

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. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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来源期刊

Movement Disorders 医学-临床神经学

CiteScore

13.30

自引率

8.10%

发文量

371

审稿时长

12 months

期刊介绍： Movement Disorders publishes a variety of content types including Reviews, Viewpoints, Full Length Articles, Historical Reports, Brief Reports, and Letters. The journal considers original manuscripts on topics related to the diagnosis, therapeutics, pharmacology, biochemistry, physiology, etiology, genetics, and epidemiology of movement disorders. Appropriate topics include Parkinsonism, Chorea, Tremors, Dystonia, Myoclonus, Tics, Tardive Dyskinesia, Spasticity, and Ataxia.