Tourette Syndrome (TS) is a neuropsychiatric disorder of complex genetic architecture involving multiple interacting genes. Here, we sought to elucidate the pathways that underlie the neurobiology of the disorder through genome-wide analysis. We analyzed genome-wide genotypic data of 3581 individuals with Tourette Syndrome (TS) and 7682 ancestry-matched controls and investigated associations of TS with sets of genes that are expressed in particular cell types and operate in specific neuronal and glial functions. We employed a self-contained, set-based association method (SBA) as well as a competitive gene set method (MAGMA) using individual-level genotype data to perform a comprehensive investigation of the biological background of TS. Our SBA analysis identified three significant gene sets after Bonferroni correction, implicating Ligand-gated Ion Channel Signaling, Lymphocytic, and Cell Adhesion and Transsynaptic Signaling processes. MAGMA analysis further supported the involvement of the Cell Adhesion and Trans-synaptic Signaling gene set. The Lymphocytic gene set was driven by variants in FLT3, raising an intriguing hypothesis for the involvement of a neuroinflammatory element in TS pathogenesis. The indications of involvement of Ligand-gated Ion Channel Signaling reinforce the role of GABA in TS, while the association of Cell Adhesion and Transsynaptic Signaling gene set provides additional support for the role of adhesion molecules in neuropsychiatric disorders.

中文翻译：

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抽动秽语综合征所涉及的突触过程和免疫相关途径

Tourette综合征（TS）是一种复杂的遗传结构涉及多个相互作用基因的神经精神疾病。在这里，我们试图通过全基因组分析来阐明该疾病的神经生物学基础。我们分析了3581例图雷特氏综合症（TS）和7682血统匹配的对照个体的全基因组基因型数据，并研究了TS与在特定细胞类型中表达并在特定神经元和神经胶质功能中起作用的基因集的关联。我们采用了独立的，基于集合的关联方法（SBA）和竞争性基因集方法（MAGMA），使用个体水平的基因型数据对TS的生物学背景进行了全面研究。我们的SBA分析确定了Bonferroni校正后的三个重要基因集，暗示配体门离子通道信号传导，淋巴细胞，细胞粘附和突触传递信号过程。MAGMA分析进一步支持了细胞粘附和跨突触信号基因集的参与。淋巴细胞基因组是由FLT3中的变体驱动的，提出了一个有趣的假设，即神经炎性因子参与TS发病机制。配体门离子通道信号的参与的迹象加强了GABA在TS中的作用，而细胞粘附与转突触信号基因集的关联为粘附分子在神经精神疾病中的作用提供了额外的支持。淋巴细胞基因组是由FLT3中的变体驱动的，提出了一个有趣的假设，即神经炎性因子参与TS发病机制。配体门离子通道信号的参与的迹象加强了GABA在TS中的作用，而细胞粘附与转突触信号基因集的关联为粘附分子在神经精神疾病中的作用提供了额外的支持。淋巴细胞基因组是由FLT3中的变体驱动的，提出了一个有趣的假设，即神经炎性因子参与TS发病机制。配体门离子通道信号的参与的迹象加强了GABA在TS中的作用，而细胞粘附与转突触信号基因集的关联为粘附分子在神经精神疾病中的作用提供了额外的支持。