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; 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; Sabrina Darrow; Roger Kurlan; James F Leckman; Jan H Smit; Harald Aschauer Harald Aschauer; Anastasios Konstantinidis; Kirsten Müller-Vahl; Tomasz Wolanczyk; 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; A. Jeremy Willsey; Samuel Zinner; Thomas Fernandez; Gary Heiman; Psychiat Genomics Consortium Toure; Pieter Hoekstra; Jay Tischfield; Douglas Woods

doi:10.1038/s41398-020-01082-z

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Synaptic processes and immune-related pathways implicated in Tourette syndrome

Journal article

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Peer reviewed

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, …

Translational psychiatry, Vol.11(1), pp.56-56

2021-01-18

DOI: https://doi.org/10.1038/s41398-020-01082-z

PMID: 33462189

Abstract

Comparative genomics

Molecular neuroscience

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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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.21 Psychiatry; 1.21.952 Obsessive-Compulsive Disorder
Web Of Science research areas: Psychiatry
ESI research areas: Psychiatry/Psychology

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Title: Synaptic processes and immune-related pathways implicated in Tourette syndrome
Creators: Fotis Tsetsos - Alexandroupolis, Greece
Dongmei Yu - Boston, MA USA
Jae Hoon Sul - Los Angeles, CA USA
Alden Y Huang - Los Angeles, CA USA
Cornelia Illmann - Boston, MA USA
Lisa Osiecki - Boston, MA USA
Sabrina M Darrow - San Francisco, CA USA
Matthew E Hirschtritt - San Francisco, CA USA
Erica Greenberg - Boston, MA USA
Kirsten R Muller-Vahl - Hannover, Germany
Manfred Stuhrmann - Hannover, Germany
Yves Dion - McGill University Health Center, University of Montreal, McGill University Health Centre, Montreal, Canada
Guy A Rouleau - Montreal, Canada
Harald Aschauer - Vienna, Austria
Mara Stamenkovic - Vienna, Austria
Monika Schlögelhofer - Biopsychosocial Corporation, Vienna, Austria
Paul Sandor - Toronto, Canada
Cathy L Barr - Toronto, Canada
Marco A Grados - Baltimore, MD USA
Harvey S Singer - Baltimore, MD USA
Markus M Nöthen - Bonn, Germany
Johannes Hebebrand - Essen, Germany
Anke Hinney - Essen, Germany
Robert A King - New Haven, CT USA
Thomas V Fernandez - New Haven, CT USA
Csaba Barta - Budapest, Hungary
Zsanett Tarnok - Vadaskert Child and Adolescent Psychiatric Hospital, Budapest, Hungary
Peter Nagy - Vadaskert Child and Adolescent Psychiatric Hospital, Budapest, Hungary
Christel Depienne - Institute of Human Genetics, University Hospital Essen, University Duisburg-Essen, Essen, Germany
Yulia Worbe - UMR S 1127, CNRS UMR 7225 ICM Paris, France
Andreas Hartmann - UMR S 1127, CNRS UMR 7225 ICM Paris, France
Cathy L Budman - Hempstead, NY USA
Renata Rizzo - Catania, Italy
Gholson J Lyon - Staten Island, NY USA
William M McMahon - Salt Lake City, UT USA
James R Batterson - Kansas City, MO USA
Danielle C Cath - Groningen, the Netherlands
Irene A Malaty - Gainesville, FL USA
Michael S Okun - Gainesville, FL USA
Cheston Berlin - Hershey, PA USA
Douglas W Woods - Milwaukee, WI USA
Paul C Lee - Honolulu, HI USA
Joseph Jankovic - Houston, TX USA
Mary M Robertson - London, UK
Donald L Gilbert - Cincinnati, USA
Lawrence W Brown - Philadelphia, PA USA
Barbara J Coffey - Miami, FL USA
Andrea Dietrich - Department of Child and Adolescent Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
Pieter J Hoekstra - Department of Child and Adolescent Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
Samuel Kuperman - Iowa City, IA USA
Samuel H Zinner - Seattle, WA USA
Michael Wagner - Bonn, Germany
James A Knowles - Brooklyn, NY USA
A Jeremy Willsey - San Francisco, CA USA
Jay A Tischfield - Piscataway, NJ USA
Gary A Heiman - Piscataway, NJ USA
Nancy J Cox - Nashville, TN USA
Nelson B Freimer - Los Angeles, CA USA
Benjamin M Neale - Boston, MA USA
Lea K Davis - Nashville, TN USA
Giovanni Coppola - Los Angeles, CA USA
Carol A Mathews - Gainesville, FL USA
Jeremiah M Scharf - Boston, MA USA
Peristera Paschou - West Lafayette, IN USA
Giovanni Coppola - Los Angeles, CA USA
Sabrina Darrow - San Francisco, CA USA
Lea K Davis - Nashville, TN USA
Yves Dion - McGill University Health Center, University of Montreal, McGill University Health Centre, Montreal, Canada
Nelson B Freimer - Los Angeles, CA USA
Erica Greenberg - Boston, MA USA
Roger Kurlan - Summit, NJ USA
James F Leckman - New Haven, CT USA
Gholson J Lyon - Staten Island, NY USA
Irene A Malaty - Gainesville, FL USA
Benjamin M Neale - Boston, MA USA
Michael S Okun - Gainesville, FL USA
Guy A Rouleau - Montreal, Canada
Jan H Smit - Amsterdam, The Netherlands
Harald Aschauer Harald Aschauer - Vienna, Austria
Csaba Barta - Budapest, Hungary
Christel Depienne - Institute of Human Genetics, University Hospital Essen, University Duisburg-Essen, Essen, Germany
Anastasios Konstantinidis - Vienna, Austria
Kirsten Müller-Vahl - Hannover, Germany
Peristera Paschou - West Lafayette, IN USA
Fotis Tsetsos - Alexandroupolis, Greece
Tomasz Wolanczyk - 00-001 Warsaw, Poland
Yulia Worbe - UMR S 1127, CNRS UMR 7225 ICM Paris, France
Lawrence Brown - Philadelphia, PA USA
Keun-Ah Cheon - Seoul, South Korea
Thomas V Fernandez - New Haven, CT USA
Blanca Garcia-Delgar - Barcelona, Spain
Donald Gilbert - Cincinnati, USA
Dorothy E Grice - New York, NY USA
Julie Hagstrøm - Copenhagen, Denmark
Tammy Hedderly - London, UK
Gary A Heiman - Piscataway, NJ USA
Isobel Heyman - London, UK
Chaim Huyser - Amsterdam, The Netherlands
Young Key Kim - Yonsei Bom Clinic, Seoul, South Korea
Young-Shin Kim - San Francisco, CA USA
Yun-Joo Koh - The Korea Institute for Children’s Social Development, Rudolph Child Research Center, Seoul, South Korea
Sodahm Kook - Seoul, South Korea
Bennett L Leventhal - San Francisco, CA USA
Marcos Madruga-Garrido - Seville, Spain
Pablo Mir - Sevilla, Spain
Astrid Morer - Barcelona, Spain
Alexander Münchau - Lübeck, Germany
Kerstin J Plessen - Copenhagen, Denmark
Veit Roessner - Dresden, Germany
Eun-Young Shin - Seoul, South Korea
Dong-Ho Song - Seoul, South Korea
Jungeun Song - Goyang-Si, South Korea
A. Jeremy Willsey - San Francisco, CA USA
Samuel Zinner - Seattle, WA USA
Harald Aschauer - Vienna, Austria
Thomas Fernandez - New Haven, CT USA
Gary Heiman - Piscataway, NJ USA
Psychiat Genomics Consortium Toure
Pieter Hoekstra - Department of Child and Adolescent Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
Jay Tischfield - Piscataway, NJ USA
Douglas Woods - Milwaukee, WI USA
Yulia Worbe - UMR S 1127, CNRS UMR 7225 ICM Paris, France
Publication Details: Translational psychiatry, Vol.11(1), pp.56-56
Publisher: Nature Publishing Group UK
Grant note: ;
Academic Unit: Miller School of Medicine; UMMG Dept of Psychiatry & Behavioral Sciences
Language: English
Resource Type: Journal article
PMID: 33462189
Record Identifier: 991031599399002976