Lübeck Interdisciplinary Platform for Genome Analytics, Institutes of Neurogenetics and Cardiogenetics, University of Lübeck, Lübeck, Germany.
Institute of Neurogenetics, University of Lübeck, Lübeck, Germany.
Parkinsonism Relat Disord. 2018 Dec;57:50-57. doi: 10.1016/j.parkreldis.2018.07.018. Epub 2018 Jul 27.
Dystonia is a genetically complex disease with both monogenic and polygenic causes. For the latter, numerous genetic associations studies have been performed with largely inconsistent results. The aim of this study was to perform a field synopsis including systematic meta-analyses of genetic association studies in isolated dystonia.
For the field synopsis we systematically screened and scrutinized the published literature using NCBI's PubMed database. For genetic variants with sufficient information in at least two independent datasets, random-effects meta-analyses were performed, including meta-analyses stratified by ethnic descent and dystonia subtypes.
A total of 3575 articles were identified and scrutinized resulting in the inclusion of 42 independent publications allowing 134 meta-analyses on 45 variants across 17 genes. While our meta-analyses pinpointed several association signals with variants in TOR1A, DRD1, and ARSG, no single variant displayed compelling association with dystonia in the available data.
Our study provides an up-to-date summary of the status of dystonia genetic association studies. Additional large-scale studies are needed to better understand the genetic causes of isolated dystonia.
肌张力障碍是一种遗传复杂的疾病，既有单基因病因，也有多基因病因。对于后者，已经进行了许多遗传关联研究，但结果大多不一致。本研究旨在对孤立性肌张力障碍的遗传关联研究进行领域综述，包括系统的荟萃分析。
为了进行领域综述，我们使用 NCBI 的 PubMed 数据库系统地筛选和审查了已发表的文献。对于至少有两个独立数据集提供了足够信息的遗传变异，我们进行了随机效应荟萃分析，包括按种族和肌张力障碍亚型分层的荟萃分析。
共确定了 3575 篇文章，并进行了审查，最终纳入了 42 项独立出版物，允许对 17 个基因中的 45 个变异进行 134 项荟萃分析。虽然我们的荟萃分析指出了 TOR1A、DRD1 和 ARSG 中几个与变异相关的关联信号，但在现有数据中，没有单个变异显示出与肌张力障碍的强烈关联。
本研究提供了肌张力障碍遗传关联研究现状的最新总结。需要进行更多的大规模研究，以更好地了解孤立性肌张力障碍的遗传原因。
