Portal de Periódicos da CAPES

Synaptic processes and immune-related pathways implicated in Tourette syndrome

2021; Springer Nature; Volume: 11; Issue: 1 Linguagem: Inglês

10.1038/s41398-020-01082-z

2158-3188

Fotis Tsetsos, Dongmei Yu, Jae Hoon Sul, Alden Y. Huang, Cornelia Illmann, Lisa Osiecki, Sabrina M. Darrow, Matthew E. Hirschtritt, Erica Greenberg, Kirsten Müller‐Vahl, Manfred Stuhrmann, Yves Dion, Guy A. Rouleau, H.N. Aschauer, M. Stamenković, Monika Schlögelhofer, Paul Sandor, Cathy L. Barr, Marco A. Grados, Harvey S. Singer, Markus M. Nöthen, Johannes Hebebrand, Anke Hinney, Robert A. King, Thomas Fernandez, Csaba Barta, Zsanett Tárnok, Péter Nagy, Christel Depienne, Yulia Worbe, Andreas Hartmann, Cathy L. Budman, Renata Rizzo, Gholson J. Lyon, William M. McMahon, James R. Batterson, Daniëlle C. Cath, Irene A. Malaty, Michael S. Okun, Cheston M. 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, Cathy L. Barr, James R. Batterson, Cheston M. Berlin, Cathy L. Budman, Daniëlle C. Cath, Giovanni Coppola, Nancy J. Cox, Sabrina M. Darrow, Lea K. Davis, Yves Dion, Nelson B. Freimer, Marco A. Grados, Erica Greenberg, Matthew E. Hirschtritt, Alden Y. Huang, Cornelia Illmann, Robert A. King, Roger Kurlan, James F. Leckman, Gholson J. Lyon, Irene A. Malaty, Carol A. Mathews, William M. McMahon, Benjamin M. Neale, Michael S. Okun, Lisa Osiecki, Mary M. Robertson, Guy A. Rouleau, Paul Sandor, Jeremiah M. Scharf, Harvey S. Singer, Jan Smit, Jae Hoon Sul, Dongmei Yu, Harald Aschauer Harald Aschauer, Csaba Barta, Cathy L. Budman, Daniëlle C. Cath, Christel Depienne, Andreas Hartmann, Johannes Hebebrand, Anastasios Konstantinidis, Carol A. Mathews, Kirsten Müller‐Vahl, Péter Nagy, Markus M. Nöthen, Peristera Paschou, Renata Rizzo, Guy A. Rouleau, Paul Sandor, Jeremiah M. Scharf, Monika Schlögelhofer, M. Stamenković, Manfred Stuhrmann, Fotis Tsetsos, Zsanett Tárnok, Tomasz Wolañczyk, Yulia Worbe, Lawrence W. Brown, Keun‐Ah Cheon, Barbara J. Coffey, Andrea Dietrich, Thomas Fernandez, Blanca García-Delgar, Donald L. Gilbert, Dorothy E. Grice, Julie Hagstrøm, Tammy Hedderly, Gary A. Heiman, Isobel Heyman, Pieter J. Hoekstra, Chaim Huyser, Young Key Kim, Young‐Shin Kim, Robert A. King, Yun‐Joo Koh, Sodahm Kook, Samuel Kuperman, Bennett Leventhal, Marcos Madruga‐Garrido, Pablo Mir, Àstrid Morer, Alexander Münchau, Kerstin Jessica Plessen, Veit Roessner, Eun‐Young Shin, Dong‐Ho Song, Jungeun Song, Jay A. Tischfield, A. Jeremy Willsey, Samuel H. Zinner, H.N. Aschauer, Cathy L. Barr, Csaba Barta, James R. Batterson, Cheston M. Berlin, Lawrence W. Brown, Cathy L. Budman, Daniëlle C. Cath, Barbara J. Coffey, Giovanni Coppola, Nancy J. Cox, Sabrina M. Darrow, Lea K. Davis, Christel Depienne, Andrea Dietrich, Yves Dion, Thomas Fernandez, Nelson B. Freimer, Donald L. Gilbert, Marco A. Grados, Erica Greenberg, Andreas Hartmann, Johannes Hebebrand, Gary A. Heiman, Matthew E. Hirschtritt, Pieter J. Hoekstra, Alden Y. Huang, Cornelia Illmann, Joseph Jankovic, Robert A. King, Samuel Kuperman, Paul C. Lee, Gholson J. Lyon, Irene A. Malaty, Carol A. Mathews, William M. McMahon, Kirsten Müller‐Vahl, Péter Nagy, Benjamin M. Neale, Markus M. Nöthen, Michael S. Okun, Lisa Osiecki, Peristera Paschou, Renata Rizzo, Mary M. Robertson, Guy A. Rouleau, Paul Sandor, Jeremiah M. Scharf, Monika Schlögelhofer, Harvey S. Singer, M. Stamenković, Manfred Stuhrmann, Jae Hoon Sul, Zsanett Tárnok, Jay A. Tischfield, Fotis Tsetsos, A. Jeremy Willsey, Douglas W. Woods, Yulia Worbe, Dongmei Yu, Samuel H. Zinner,

Autism Spectrum Disorder Research

Abstract 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.