The Genetic Etiology of Tourette Syndrome: Large-Scale Collaborative Efforts on the Precipice of Discovery.
The Genetic Etiology of Tourette Syndrome: Large-Scale Collaborative Efforts on the Precipice of Discovery.
复制标题
DOI：
10.3389/fnins.2016.00351
复制
发表时间：
2016
影响因子：
4.3
通讯作者：
Paschou P
中科院分区：
文献类型：
--
作者：
Georgitsi M;Willsey AJ;Mathews CA;State M;Scharf JM;Paschou P
抽动秽语综合征（TS）是一种儿童期发病的神经发育障碍，其特征是多发性运动和语音抽搐。它具有复杂的病因学，多个基因可能与环境因素相互作用，导致症状的发作。这种疾病的遗传基础仍然难以捉摸。然而，多种资源和大型项目正在汇集在一起，开启了该领域的新时代，并将我们带到了发现的边缘。本报告中概述的大规模努力是互补的，代表了复杂遗传疾病研究的一系列不同方法。Tourette综合征协会国际遗传学联盟（TSAICG）专注于大家庭，父母-先证者三人组和大型病例对照设计的病例，如全基因组关联研究（GWAS），拷贝数变异（CNV）扫描和外显子组/基因组测序。TIC Genetics的目标是单一三代和多代家庭中罕见的大效应量突变。欧洲多中心儿童抽动症研究（EMTICS）旨在阐明基因-环境相互作用，包括TS病因学中感染和免疫机制的参与。最后，玛丽·居里初期培训网络TS-EUROTRAIN旨在作为一个平台，统一该领域的大型项目，并教育下一代专家。重要的是，这些互补的大规模努力正在联合起来，揭示TS的全部遗传变异和环境风险因素，为确定确定TS易感基因和揭示这种疾病的复杂病理生理学提供了巨大的希望。
Gilles de la Tourette Syndrome (TS) is a childhood-onset neurodevelopmental disorder that is characterized by multiple motor and phonic tics. It has a complex etiology with multiple genes likely interacting with environmental factors to lead to the onset of symptoms. The genetic basis of the disorder remains elusive. However, multiple resources and large-scale projects are coming together, launching a new era in the field and bringing us on the verge of discovery. The large-scale efforts outlined in this report are complementary and represent a range of different approaches to the study of disorders with complex inheritance. The Tourette Syndrome Association International Consortium for Genetics (TSAICG) has focused on large families, parent-proband trios and cases for large case-control designs such as genomewide association studies (GWAS), copy number variation (CNV) scans, and exome/genome sequencing. TIC Genetics targets rare, large effect size mutations in simplex trios, and multigenerational families. The European Multicentre Tics in Children Study (EMTICS) seeks to elucidate gene-environment interactions including the involvement of infection and immune mechanisms in TS etiology. Finally, TS-EUROTRAIN, a Marie Curie Initial Training Network, aims to act as a platform to unify large-scale projects in the field and to educate the next generation of experts. Importantly, these complementary large-scale efforts are joining forces to uncover the full range of genetic variation and environmental risk factors for TS, holding great promise for identifying definitive TS susceptibility genes and shedding light into the complex pathophysiology of this disorder.