Institute of Medical Biometry and Statistics, University of Lübeck, Lübeck, Germany.
Institute of Neurogenetics, University of Lübeck, Lübeck, Germany.
Mov Disord. 2024 Nov;39(11):2110-2116. doi: 10.1002/mds.29968. Epub 2024 Sep 17.
Despite considerable heritability, previous smaller genome-wide association studies (GWASs) have not identified any robust genetic risk factors for isolated dystonia.
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.
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.
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.
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.
尽管遗传率相当高，但之前较小规模的全基因组关联研究（GWAS）并未确定任何针对孤立性肌张力障碍的稳健遗传风险因素。
本研究旨在对一个经过充分特征描述的、多中心的超过 6000 名个体的样本进行大规模 GWAS，以确定孤立性肌张力障碍的遗传风险因素。
对 4303 名肌张力障碍患者和 2362 名欧洲血统的健康对照者的常染色体进行基于阵列的 GWAS，并基于发病年龄、受影响的身体区域和新开发的临床评分进行亚组分析。另外 736 人用于验证。
尽管有足够的检测能力来检测有意义的影响，但该 GWAS 未确定任何常见的全基因组显著位点可以复制。效能分析表明，单个变异的影响可能非常小。
基于中度单核苷酸多态性的遗传率表明，在本队列中，常见变异并未导致孤立性肌张力障碍。基于序列的 GWAS（例如，全基因组测序）可能有助于更好地理解遗传基础。 © 2024 作者。运动障碍协会由 Wiley 期刊出版公司代表国际帕金森和运动障碍协会出版。
