Synaptic processes and immune-related pathways implicated in Tourette syndrome.
Synaptic processes and immune-related pathways implicated in Tourette syndrome.
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DOI：
10.1038/s41398-020-01082-z
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发表时间：
2021-01-18
影响因子：
6.8
通讯作者：
Zinner S
中科院分区：
文献类型：
--
作者：
Tsetsos F;Yu D;Sul JH;Huang AY;Illmann C;Osiecki L;Darrow SM;Hirschtritt ME;Greenberg E;Muller-Vahl KR;Stuhrmann M;Dion Y;Rouleau GA;Aschauer H;Stamenkovic M;Schlögelhofer M;Sandor P;Barr CL;Grados MA;Singer HS;Nöthen MM;Hebebrand J;Hinney A;King RA;Fernandez TV;Barta C;Tarnok Z;Nagy P;Depienne C;Worbe Y;Hartmann A;Budman CL;Rizzo R;Lyon GJ;McMahon WM;Batterson JR;Cath DC;Malaty IA;Okun MS;Berlin C;Woods DW;Lee PC;Jankovic J;Robertson MM;Gilbert DL;Brown LW;Coffey BJ;Dietrich A;Hoekstra PJ;Kuperman S;Zinner SH;Wagner M;Knowles JA;Jeremy Willsey A;Tischfield JA;Heiman GA;Cox NJ;Freimer NB;Neale BM;Davis LK;Coppola G;Mathews CA;Scharf JM;Paschou P;Tourette Association of America International Consortium for Genetics;Barr CL;Batterson JR;Berlin C;Budman CL;Cath DC;Coppola G;Cox NJ;Darrow S;Davis LK;Dion Y;Freimer NB;Grados MA;Greenberg E;Hirschtritt ME;Huang AY;Illmann C;King RA;Kurlan R;Leckman JF;Lyon GJ;Malaty IA;Mathews CA;McMahon WM;Neale BM;Okun MS;Osiecki L;Robertson MM;Rouleau GA;Sandor P;Scharf JM;Singer HS;Smit JH;Sul JH;Yu D;Gilles de la Tourette GWAS Replication Initiative;Aschauer HAH;Barta C;Budman CL;Cath DC;Depienne C;Hartmann A;Hebebrand J;Konstantinidis A;Mathews CA;Müller-Vahl K;Nagy P;Nöthen MM;Paschou P;Rizzo R;Rouleau GA;Sandor P;Scharf JM;Schlögelhofer M;Stamenkovic M;Stuhrmann M;Tsetsos F;Tarnok Z;Wolanczyk T;Worbe Y;Tourette International Collaborative Genetics Study;Brown L;Cheon KA;Coffey BJ;Dietrich A;Fernandez TV;Garcia-Delgar B;Gilbert D;Grice DE;Hagstrøm J;Hedderly T;Heiman GA;Heyman I;Hoekstra PJ;Huyser C;Kim YK;Kim YS;King RA;Koh YJ;Kook S;Kuperman S;Leventhal BL;Madruga-Garrido M;Mir P;Morer A;Münchau A;Plessen KJ;Roessner V;Shin EY;Song DH;Song J;Tischfield JA;Willsey AJ;Zinner S;Psychiatric Genomics Consortium Tourette Syndrome Working Group;Aschauer H;Barr CL;Barta C;Batterson JR;Berlin C;Brown L;Budman CL;Cath DC;Coffey BJ;Coppola G;Cox NJ;Darrow S;Davis LK;Depienne C;Dietrich A;Dion Y;Fernandez T;Freimer NB;Gilbert D;Grados MA;Greenberg E;Hartmann A;Hebebrand J;Heiman G;Hirschtritt ME;Hoekstra P;Huang AY;Illmann C;Jankovic J;King RA;Kuperman S;Lee PC;Lyon GJ;Malaty IA;Mathews CA;McMahon WM;Müller-Vahl K;Nagy P;Neale BM;Nöthen MM;Okun MS;Osiecki L;Paschou P;Rizzo R;Robertson MM;Rouleau GA;Sandor P;Scharf JM;Schlögelhofer M;Singer HS;Stamenkovic M;Stuhrmann M;Sul JH;Tarnok Z;Tischfield J;Tsetsos F;Willsey AJ;Woods D;Worbe Y;Yu D;Zinner S
图雷特综合征（TS）是一种具有复杂遗传结构的神经精神障碍，涉及多个相互作用的基因。在此，我们试图通过全基因组分析来阐明该疾病神经生物学基础的相关通路。我们分析了3581名图雷特综合征患者和7682名血统匹配的对照者的全基因组基因型数据，并研究了图雷特综合征与在特定细胞类型中表达且在特定神经元和神经胶质功能中起作用的基因集之间的关联。我们使用了一种基于集合的自包含关联方法（SBA）以及一种基于个体水平基因型数据的竞争性基因集方法（MAGMA），对图雷特综合征的生物学背景进行了全面研究。我们的SBA分析在邦费罗尼校正后确定了三个显著的基因集，涉及配体门控离子通道信号传导、淋巴细胞以及细胞黏附和跨突触信号传导过程。MAGMA分析进一步支持了细胞黏附和跨突触信号传导基因集的参与。淋巴细胞基因集是由FLT3中的变异驱动的，这为神经炎症因素参与图雷特综合征发病机制提出了一个有趣的假设。配体门控离子通道信号传导参与的迹象强化了γ -氨基丁酸（GABA）在图雷特综合征中的作用，而细胞黏附和跨突触信号传导基因集的关联为黏附分子在神经精神障碍中的作用提供了额外支持。这项研究强化了先前的发现，同时也为图雷特综合征的神经生物学提供了新的见解。
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 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 trans-synaptic signaling gene set provides additional support for the role of adhesion molecules in neuropsychiatric disorders. This study reinforces previous findings but also provides new insights into the neurobiology of TS.
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影响因子：
6.2
作者：
Autism Spectrum Disorders Working Group of The Psychiatric Genomics Consortium
通讯作者：
Autism Spectrum Disorders Working Group of The Psychiatric Genomics Consortium
影响因子：
9.2
作者：
Chang CC;Chow CC;Tellier LC;Vattikuti S;Purcell SM;Lee JJ
通讯作者：
Lee JJ
影响因子：
64.5
作者：
Astle, William J.;Elding, Heather;Soranzo, Nicole
通讯作者：
Soranzo, Nicole
NRXN1和CNTN6中的罕见拷贝数变体增加了Tourette综合征的风险。
影响因子：
16.2
作者：
Huang AY;Yu D;Davis LK;Sul JH;Tsetsos F;Ramensky V;Zelaya I;Ramos EM;Osiecki L;Chen JA;McGrath LM;Illmann C;Sandor P;Barr CL;Grados M;Singer HS;Nöthen MM;Hebebrand J;King RA;Dion Y;Rouleau G;Budman CL;Depienne C;Worbe Y;Hartmann A;Müller-Vahl KR;Stuhrmann M;Aschauer H;Stamenkovic M;Schloegelhofer M;Konstantinidis A;Lyon GJ;McMahon WM;Barta C;Tarnok Z;Nagy P;Batterson JR;Rizzo R;Cath DC;Wolanczyk T;Berlin C;Malaty IA;Okun MS;Woods DW;Rees E;Pato CN;Pato MT;Knowles JA;Posthuma D;Pauls DL;Cox NJ;Neale BM;Freimer NB;Paschou P;Mathews CA;Scharf JM;Coppola G;Tourette Syndrome Association International Consortium for Genetics (TSAICG);Gilles de la Tourette Syndrome GWAS Replication Initiative (GGRI)
通讯作者：
Gilles de la Tourette Syndrome GWAS Replication Initiative (GGRI)
影响因子：
12.3
作者：
Idaghdour Y;Hodgkinson A
通讯作者：
Hodgkinson A