Department of Molecular Biology and Genetics, Democritus University of Thrace, Alexandroupolis, Greece.
Department of Biological Sciences, Purdue University, West Lafayette, Indiana.
Biol Psychiatry. 2024 Jul 15;96(2):114-124. doi: 10.1016/j.biopsych.2023.01.023. Epub 2023 Feb 2.
Tourette syndrome (TS) is a childhood-onset neurodevelopmental disorder of complex genetic architecture and is characterized by multiple motor tics and at least one vocal tic persisting for more than 1 year.
We performed a genome-wide meta-analysis integrating a novel TS cohort with previously published data, resulting in a sample size of 6133 individuals with TS and 13,565 ancestry-matched control participants.
We identified a genome-wide significant locus on chromosome 5q15. Integration of expression quantitative trait locus, Hi-C (high-throughput chromosome conformation capture), and genome-wide association study data implicated the NR2F1 gene and associated long noncoding RNAs within the 5q15 locus. Heritability partitioning identified statistically significant enrichment in brain tissue histone marks, while polygenic risk scoring of brain volume data identified statistically significant associations with right and left thalamus volumes and right putamen volume.
Our work presents novel insights into the neurobiology of TS, thereby opening up new directions for future studies.
妥瑞氏综合征（TS）是一种儿童期发病的神经发育障碍，具有复杂的遗传结构，其特征是多种运动性抽搐和至少一种持续性超过 1 年的发声性抽搐。
我们进行了一项全基因组荟萃分析，将一个新的 TS 队列与之前发表的数据结合起来，样本量为 6133 名 TS 患者和 13565 名匹配的对照组参与者。
我们在 5 号染色体 q15 上发现了一个全基因组显著的位置。表达数量性状基因座、Hi-C（高通量染色体构象捕获）和全基因组关联研究数据的整合表明，NR2F1 基因及其在 5q15 位置的相关长非编码 RNA 存在关联性。遗传力分割确定了脑组织组蛋白标记的统计学上显著富集，而大脑体积数据的多基因风险评分确定了与右侧和左侧丘脑体积以及右侧壳核体积的统计学显著关联。
我们的工作为妥瑞氏综合征的神经生物学提供了新的见解，从而为未来的研究开辟了新的方向。
