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Journal Articles Translational Psychiatry Year : 2021

Synaptic processes and immune-related pathways implicated in Tourette syndrome

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 (1) , Yulia Worbe (1, 2) , Andreas Hartmann (1) , 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 , Cathy L Barr , James R Batterson , Cheston Berlin , Cathy L Budman , Danielle 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 H Smit , Jae Hoon Sul , Dongmei Yu , Harald Aschauer Harald Aschauer , Csaba Barta , Cathy L Budman , Danielle C Cath , Christel Depienne , Andreas Hartmann , Johannes Hebebrand , Anastasios Konstantinidis , Carol A Mathews , Kirsten R Muller-Vahl , Peter Nagy , Markus M Nöthen , Peristera Paschou , Renata Rizzo , Guy A Rouleau , Paul Sandor , Jeremiah M Scharf , Monika Schlögelhofer , Mara Stamenkovic , Manfred Stuhrmann , Fotis Tsetsos , Zsanett Tarnok , Tomasz Wolanczyk , Yulia Worbe , Lawrence W Brown , Keun-Ah Cheon , Barbara J Coffey , Andrea Dietrich , Thomas V Fernandez , Blanca Garcia-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 L Leventhal , Marcos Madruga-Garrido , Pablo Mir , Astrid Morer , Alexander Münchau , Kerstin J Plessen , Veit Roessner , Eun-Young Shin , Dong-Ho Song , Jungeun Song , Jay A Tischfield , A. Jeremy Willsey , Samuel H Zinner , Harald Aschauer , Cathy L Barr , Csaba Barta , James R Batterson , Cheston Berlin , Lawrence W Brown , Cathy L Budman , Danielle C Cath , Barbara J Coffey , Giovanni Coppola , Nancy J Cox , Sabrina M Darrow , Lea K Davis , Christel Depienne , Andrea Dietrich , Yves Dion , Thomas V 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 R Muller-Vahl , Peter 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 , Mara Stamenkovic , Manfred Stuhrmann , Jae Hoon Sul , Zsanett Tarnok , Jay A Tischfield , Fotis Tsetsos , A. Jeremy Willsey , Douglas W Woods , Yulia Worbe , Dongmei Yu , Samuel H Zinner
Fotis Tsetsos
Dongmei Yu
  • Function : Author
Jae Hoon Sul
  • Function : Author
Alden Y Huang
  • Function : Author
Cornelia Illmann
  • Function : Author
Lisa Osiecki
  • Function : Author
Sabrina M Darrow
  • Function : Author
Matthew E Hirschtritt
  • Function : Author
Erica Greenberg
Kirsten R Muller-Vahl
Manfred Stuhrmann
  • Function : Author
Yves Dion
Guy A Rouleau
Harald Aschauer
Mara Stamenkovic
  • Function : Author
Monika Schlögelhofer
  • Function : Author
Paul Sandor
  • Function : Author
Cathy L Barr
  • Function : Author
Marco A Grados
  • Function : Author
Harvey S Singer
  • Function : Author
Markus M Nöthen
  • Function : Author
Johannes Hebebrand
  • Function : Author
Anke Hinney
  • Function : Author
Robert A King
  • Function : Author
Thomas V Fernandez
Csaba Barta
Zsanett Tarnok
  • Function : Author
Peter Nagy
  • Function : Author
Cathy L Budman
  • Function : Author
Renata Rizzo
  • Function : Author
Gholson J Lyon
William M Mcmahon
  • Function : Author
James R Batterson
  • Function : Author
Danielle C Cath
  • Function : Author
Irene A Malaty
Michael S Okun
Cheston Berlin
  • Function : Author
Douglas W Woods
  • Function : Author
Paul C Lee
  • Function : Author
Joseph Jankovic
  • Function : Author
Mary M Robertson
  • Function : Author
Donald L Gilbert
  • Function : Author
Lawrence W Brown
  • Function : Author
Barbara J Coffey
  • Function : Author
Andrea Dietrich
  • Function : Author
Pieter J Hoekstra
  • Function : Author
Samuel Kuperman
  • Function : Author
Samuel H Zinner
  • Function : Author
Michael Wagner
James A Knowles
  • Function : Author
A. Jeremy Willsey
  • Function : Author
Jay A Tischfield
  • Function : Author
Gary A Heiman
Nancy J Cox
  • Function : Author
Nelson B Freimer
Benjamin M Neale
Lea K Davis
Giovanni Coppola
Carol A Mathews
  • Function : Author
Jeremiah M Scharf
  • Function : Author
Peristera Paschou
Cathy L Barr
  • Function : Author
James R Batterson
  • Function : Author
Cheston Berlin
  • Function : Author
Cathy L Budman
  • Function : Author
Danielle C Cath
  • Function : Author
Giovanni Coppola
  • Function : Author
Nancy J Cox
  • Function : Author
Sabrina M Darrow
  • Function : Author
Lea K Davis
  • Function : Author
Yves Dion
  • Function : Author
Nelson B Freimer
  • Function : Author
Marco A Grados
  • Function : Author
Erica Greenberg
  • Function : Author
Matthew E Hirschtritt
  • Function : Author
Alden Y Huang
  • Function : Author
Cornelia Illmann
  • Function : Author
Robert A King
  • Function : Author
Roger Kurlan
  • Function : Author
James F Leckman
  • Function : Author
Gholson J Lyon
  • Function : Author
Irene A Malaty
  • Function : Author
Carol A Mathews
  • Function : Author
William M Mcmahon
  • Function : Author
Benjamin M Neale
  • Function : Author
Michael S Okun
  • Function : Author
Lisa Osiecki
  • Function : Author
Mary M Robertson
  • Function : Author
Guy A Rouleau
  • Function : Author
Paul Sandor
  • Function : Author
Jeremiah M Scharf
  • Function : Author
Harvey S Singer
  • Function : Author
Jan H Smit
  • Function : Author
Jae Hoon Sul
  • Function : Author
Dongmei Yu
  • Function : Author
Csaba Barta
  • Function : Author
Cathy L Budman
  • Function : Author
Danielle C Cath
  • Function : Author
Christel Depienne
  • Function : Author
Andreas Hartmann
  • Function : Author
Johannes Hebebrand
  • Function : Author
Anastasios Konstantinidis
  • Function : Author
Carol A Mathews
  • Function : Author
Kirsten R Muller-Vahl
  • Function : Author
Peter Nagy
  • Function : Author
Markus M Nöthen
  • Function : Author
Peristera Paschou
  • Function : Author
Renata Rizzo
  • Function : Author
Guy A Rouleau
  • Function : Author
Paul Sandor
  • Function : Author
Jeremiah M Scharf
  • Function : Author
Monika Schlögelhofer
  • Function : Author
Mara Stamenkovic
  • Function : Author
Manfred Stuhrmann
  • Function : Author
Fotis Tsetsos
  • Function : Author
Zsanett Tarnok
  • Function : Author
Tomasz Wolanczyk
  • Function : Author
Yulia Worbe
  • Function : Author
Lawrence W Brown
  • Function : Author
Keun-Ah Cheon
  • Function : Author
Barbara J Coffey
  • Function : Author
Andrea Dietrich
  • Function : Author
Thomas V Fernandez
  • Function : Author
Blanca Garcia-Delgar
  • Function : Author
Donald L Gilbert
  • Function : Author
Dorothy E Grice
  • Function : Author
Julie Hagstrøm
  • Function : Author
Tammy Hedderly
  • Function : Author
Gary A Heiman
  • Function : Author
Isobel Heyman
  • Function : Author
Pieter J Hoekstra
  • Function : Author
Chaim Huyser
  • Function : Author
Young Key Kim
  • Function : Author
Young-Shin Kim
  • Function : Author
Robert A King
  • Function : Author
Yun-Joo Koh
  • Function : Author
Sodahm Kook
  • Function : Author
Samuel Kuperman
  • Function : Author
Bennett L Leventhal
  • Function : Author
Marcos Madruga-Garrido
  • Function : Author
Pablo Mir
  • Function : Author
Astrid Morer
  • Function : Author
Alexander Münchau
  • Function : Author
Kerstin J Plessen
  • Function : Author
Veit Roessner
  • Function : Author
Eun-Young Shin
  • Function : Author
Dong-Ho Song
  • Function : Author
Jungeun Song
  • Function : Author
Jay A Tischfield
  • Function : Author
A. Jeremy Willsey
  • Function : Author
Samuel H Zinner
  • Function : Author
Harald Aschauer
  • Function : Author
Cathy L Barr
  • Function : Author
Csaba Barta
  • Function : Author
James R Batterson
  • Function : Author
Cheston Berlin
  • Function : Author
Lawrence W Brown
  • Function : Author
Cathy L Budman
  • Function : Author
Danielle C Cath
  • Function : Author
Barbara J Coffey
  • Function : Author
Giovanni Coppola
  • Function : Author
Nancy J Cox
  • Function : Author
Sabrina M Darrow
  • Function : Author
Lea K Davis
  • Function : Author
Christel Depienne
  • Function : Author
Andrea Dietrich
  • Function : Author
Yves Dion
  • Function : Author
Thomas V Fernandez
  • Function : Author
Nelson B Freimer
  • Function : Author
Donald L Gilbert
  • Function : Author
Marco A Grados
  • Function : Author
Erica Greenberg
  • Function : Author
Andreas Hartmann
  • Function : Author
Johannes Hebebrand
  • Function : Author
Gary A Heiman
  • Function : Author
Matthew E Hirschtritt
  • Function : Author
Pieter J Hoekstra
  • Function : Author
Alden Y Huang
  • Function : Author
Cornelia Illmann
  • Function : Author
Joseph Jankovic
  • Function : Author
Robert A King
  • Function : Author
Samuel Kuperman
  • Function : Author
Paul C Lee
  • Function : Author
Gholson J Lyon
  • Function : Author
Irene A Malaty
  • Function : Author
Carol A Mathews
  • Function : Author
William M Mcmahon
  • Function : Author
Kirsten R Muller-Vahl
  • Function : Author
Peter Nagy
  • Function : Author
Benjamin M Neale
  • Function : Author
Markus M Nöthen
  • Function : Author
Michael S Okun
  • Function : Author
Lisa Osiecki
  • Function : Author
Peristera Paschou
  • Function : Author
Renata Rizzo
  • Function : Author
Mary M Robertson
  • Function : Author
Guy A Rouleau
  • Function : Author
Paul Sandor
  • Function : Author
Jeremiah M Scharf
  • Function : Author
Monika Schlögelhofer
  • Function : Author
Harvey S Singer
  • Function : Author
Mara Stamenkovic
  • Function : Author
Manfred Stuhrmann
  • Function : Author
Jae Hoon Sul
  • Function : Author
Zsanett Tarnok
  • Function : Author
Jay A Tischfield
  • Function : Author
Fotis Tsetsos
  • Function : Author
A. Jeremy Willsey
  • Function : Author
Douglas W Woods
  • Function : Author
Yulia Worbe
  • Function : Author
Dongmei Yu
  • Function : Author
Samuel H Zinner
  • Function : Author

Abstract

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.
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hal-04501439 , version 1 (12-03-2024)

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Fotis Tsetsos, Dongmei Yu, Jae Hoon Sul, Alden Y Huang, Cornelia Illmann, et al.. Synaptic processes and immune-related pathways implicated in Tourette syndrome. Translational Psychiatry, 2021, 11 (1), pp.56. ⟨10.1038/s41398-020-01082-z⟩. ⟨hal-04501439⟩
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