Synaptic processes and immune-related pathways implicated in Tourette syndrome
Autor: | Fotis Tsetsos, Dongmei Yu, Jae Hoon Sul, Alden Y. Huang, Cornelia Illmann, Lisa Osiecki, Sabrina M. Darrow, Matthew E. Hirschtritt, Erica Greenberg, Kirsten R. Muller-Vahl, Manfred Stuhrmann, Yves Dion, Guy A. Rouleau, Harald Aschauer, Mara Stamenkovic, Monika Schlögelhofer, Paul Sandor, Cathy L. Barr, Marco A. Grados, Harvey S. Singer, Markus M. Nöthen, Johannes Hebebrand, Anke Hinney, Robert A. King, Thomas V. Fernandez, Csaba Barta, Zsanett Tarnok, Peter Nagy, Christel Depienne, Yulia Worbe, Andreas Hartmann, Cathy L. Budman, Renata Rizzo, Gholson J. Lyon, William M. McMahon, James R. Batterson, Danielle C. Cath, Irene A. Malaty, Michael S. Okun, Cheston Berlin, Douglas W. Woods, Paul C. Lee, Joseph Jankovic, Mary M. Robertson, Donald L. Gilbert, Lawrence W. Brown, Barbara J. Coffey, Andrea Dietrich, Pieter J. Hoekstra, Samuel Kuperman, Samuel H. Zinner, Michael Wagner, James A. Knowles, A. Jeremy Willsey, Jay A. Tischfield, Gary A. Heiman, Nancy J. Cox, Nelson B. Freimer, Benjamin M. Neale, Lea K. Davis, Giovanni Coppola, Carol A. Mathews, Jeremiah M. Scharf, Peristera Paschou, on behalf of the Tourette Association of America International Consortium for Genetics, Sabrina Darrow, Roger Kurlan, James F. Leckman, Jan H. Smit, the Gilles de la Tourette GWAS Replication Initiative, Harald Aschauer Harald Aschauer, Anastasios Konstantinidis, Kirsten Müller-Vahl, Tomasz Wolanczyk, the Tourette International Collaborative Genetics Study, Lawrence Brown, Keun-Ah Cheon, Blanca Garcia-Delgar, Donald Gilbert, Dorothy E. Grice, Julie Hagstrøm, Tammy Hedderly, Isobel Heyman, Chaim Huyser, Young Key Kim, Young-Shin Kim, Yun-Joo Koh, Sodahm Kook, Bennett L. Leventhal, Marcos Madruga-Garrido, Pablo Mir, Astrid Morer, Alexander Münchau, Kerstin J. Plessen, Veit Roessner, Eun-Young Shin, Dong-Ho Song, Jungeun Song, Samuel Zinner, and the Psychiatric Genomics Consortium Tourette Syndrome Working Group, Thomas Fernandez, Gary Heiman, Pieter Hoekstra, Jay Tischfield, Douglas Woods |
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Přispěvatelé: | European Commission, State Scholarships Foundation, National Institutes of Health (US), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Child Psychiatry, ANS - Cellular & Molecular Mechanisms, Tourette Association of America International Consortium for Genetics, Gilles de la Tourette GWAS Replication Initiative, Tourette International Collaborative Genetics Study, Psychiatric Genomics Consortium Tourette Syndrome Working Group, Psychiatry, APH - Mental Health, APH - Methodology, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep |
Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Cell type Genotype Medizin LOCI Genome-wide association study GENE-SET ANALYSIS Biology Molecular neuroscience Tourette syndrome Article lcsh:RC321-571 TIC DISORDERS 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine medicine Humans Copy-number variation GENOME-WIDE ASSOCIATION AUTISM Cell adhesion Gene lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Biological Psychiatry Neurons COPY NUMBER VARIANTS Cell adhesion molecule Comparative genomics medicine.disease Genetic architecture 3. Good health PREVALENCE Psychiatry and Mental health 030104 developmental biology HISTIDINE-DECARBOXYLASE HEALTH Neuroscience 030217 neurology & neurosurgery SYSTEM Genome-Wide Association Study Tourette Syndrome |
Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname Translational Psychiatry, 11(1):56. Nature Publishing Group Translational psychiatry, 11(1):56. Nature Publishing Group Translational Psychiatry, Vol 11, Iss 1, Pp 1-12 (2021) Translational psychiatry, vol. 11, no. 1, pp. 56 on behalf of the Tourette Association of America International Consortium for Genetics, the Gilles de la Tourette GWAS Replication Initiative, the Tourette International Collaborative Genetics Study & and the Psychiatric Genomics Consortium Tourette Syndrome Working Group 2021, ' Synaptic processes and immune-related pathways implicated in Tourette syndrome ', Translational psychiatry, vol. 11, no. 1, 56 . https://doi.org/10.1038/s41398-020-01082-z Translational psychiatry, 11(1):56 Translational Psychiatry |
ISSN: | 2158-3188 |
Popis: | Tsetsos, Fotis et al. 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. This research is co-financed by Greece and the European Union (European Social Fund—ESF) through the Operational Programme «Human Resources Development, Education and Lifelong Learning» in the context of the project “Reinforcement of Postdoctoral Researchers - 2nd Cycle” (MIS-5033021), implemented by the State Scholarships Foundation (IKY). L.K.D. was supported by grants from the National Institutes of Health including U54MD010722-04, R01NS102371, R01MH113362, U01HG009086, R01MH118223, DP2HD98859, R01DC16977, R01NS105746, R56MH120736, R21HG010652, and RM1HG009034. |
Databáze: | OpenAIRE |
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