Journal article
Synaptic processes and immune-related pathways implicated in Tourette syndrome
Translational psychiatry, Vol.11(1), pp.56-56
01/18/2021
DOI: 10.1038/s41398-020-01082-z
PMCID: PMC7814139
PMID: 33462189
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.
Details
- Title: Subtitle
- Synaptic processes and immune-related pathways implicated in Tourette syndrome
- Creators
- Fotis Tsetsos - Democritus University of ThraceSamuel Kuperman - University of IowaDongmei Yu - Broad InstituteJae Hoon Sul - University of California, Los AngelesAlden Y Huang - University of California, Los AngelesCornelia Illmann - Harvard UniversityLisa Osiecki - Harvard UniversitySabrina M Darrow - University of California, San FranciscoMatthew E Hirschtritt - University of California, San FranciscoErica Greenberg - Harvard UniversityKirsten R Muller-Vahl - Medizinische Hochschule HannoverManfred Stuhrmann - Medizinische Hochschule HannoverYves Dion - McGill University Health CentreGuy A Rouleau - Montreal Neurological Institute and HospitalHarald Aschauer - Medical University of ViennaMara Stamenkovic - Medical University of ViennaMonika Schlögelhofer - Biopsychosocial Corporation, Vienna, AustriaHarvey S Singer - Johns Hopkins MedicinePaul Sandor - University Health NetworkMarkus M Nöthen - University Hospital BonnCathy L Barr - University Health NetworkJohannes Hebebrand - University of Duisburg-EssenMarco A Grados - Johns Hopkins MedicineAnke Hinney - University of Duisburg-EssenRobert A King - Yale UniversityThomas V Fernandez - Yale UniversityCsaba Barta - Semmelweis UniversityZsanett Tarnok - Vadaskert Child and Adolescent Psychiatric Hospital, Budapest, HungaryPeter Nagy - Vadaskert Child and Adolescent Psychiatric Hospital, Budapest, HungaryChristel Depienne - University of Duisburg-EssenYulia Worbe - Assistance Publique Hôpitaux de Paris, Hopital Saint Antoine, Paris, FranceAndreas Hartmann - Université Paris CitéCathy L Budman - Hofstra UniversityRenata Rizzo - University of CataniaGholson J Lyon - Jervis Clinic, NYS Institute for Basic Research in Developmental Disabilities (IBR), Staten Island, NY, USAWilliam M McMahon - University of UtahJames R Batterson - Children's Mercy HospitalDanielle C Cath - University Medical Center GroningenIrene A Malaty - University of Florida HealthMichael S Okun - University of Florida HealthCheston Berlin - Pennsylvania State UniversityDouglas W Woods - University of Wisconsin–MilwaukeePaul C Lee - University of Hawaiʻi at MānoaJoseph Jankovic - Baylor College of MedicineMary M Robertson - University College LondonDonald L Gilbert - Cincinnati Children's Hospital Medical CenterLawrence W Brown - Children's Hospital of PhiladelphiaBarbara J Coffey - University of MiamiAndrea Dietrich - University Medical Center GroningenPieter J Hoekstra - University Medical Center GroningenSamuel H Zinner - University of WashingtonMichael Wagner - University Hospital BonnJames A Knowles - SUNY Downstate Health Sciences UniversityA Jeremy Willsey - University of California, San FranciscoJay A Tischfield - Rutgers, The State University of New JerseyGary A Heiman - Rutgers, The State University of New JerseyNancy J Cox - Vanderbilt University Medical CenterBenjamin M Neale - Broad InstituteCarol A Mathews - University of FloridaLea K Davis - Vanderbilt University Medical CenterJeremiah M Scharf - Broad InstituteGiovanni Coppola - University of California, Los AngelesPeristera Paschou - Purdue University West LafayetteNelson B Freimer - Semel Institute for Neuroscience and Human BehaviorRoger Kurlan - Overlook Medical CenterJames F Leckman - Yale UniversityJan H Smit - Department of Psychiatry, VU UniversityMedical Center, Amsterdam, The NetherlandsAnastasios Konstantinidis - Medical University of ViennaTomasz Wolanczyk - Medical University of WarsawKeun-Ah Cheon - Yonsei UniversityBlanca Garcia-Delgar - Department of Child and Adolescent Psychiatry and Psychology, Institute of Neurosciences, Hospital Clinic Universitari, Barcelona, SpainDorothy E Grice - Icahn School of Medicine at Mount SinaiJulie Hagstrøm - University of CopenhagenTammy Hedderly - King's College LondonIsobel Heyman - Great Ormond Street Hospital for Children NHS Foundation TrustChaim Huyser - University of AmsterdamYoung Key Kim - Yonsei UniversityYoung-Shin Kim - University of California, San FranciscoYun-Joo Koh - The Korea Institute for Children's Social Development, Rudolph Child Research Center, Seoul, South KoreaSodahm Kook - Samsung (South Korea)Bennett L Leventhal - University of California, San FranciscoMarcos Madruga-Garrido - Consejo Superior de Investigaciones CientíficasPablo Mir - Centro de Investigación en Red-Enfermedades Neurodegenerativas (CIBERNED), Madrid, SpainAstrid Morer - Universitat de BarcelonaAlexander Münchau - University of LübeckKerstin J Plessen - University of LausanneVeit Roessner - Department of Child and Adolescent Psychiatry, Faculty of Medicine, University Hospital Carl Gustav CarusTU Dresden, Dresden, GermanyEun-Young Shin - Yonsei UniversityDong-Ho Song - Yonsei UniversityJungeun Song - National Health Insurance Service Ilsan HospitalA Jeremy Willsey - University of California, San FranciscoGilles de la Tourette GWAS Replication InitiativeTourette Association of America International Consortium for GeneticsTourette International Collaborative Genetics StudyPsychiatric Genomics Consortium Tourette Syndrome Working Group
- Resource Type
- Journal article
- Publication Details
- Translational psychiatry, Vol.11(1), pp.56-56
- DOI
- 10.1038/s41398-020-01082-z
- PMID
- 33462189
- PMCID
- PMC7814139
- NLM abbreviation
- Transl Psychiatry
- ISSN
- 2158-3188
- eISSN
- 2158-3188
- Grant note
- K08 MH099424 / NIMH NIH HHS R01 NS102371 / NINDS NIH HHS RM1 HG009034 / NHGRI NIH HHS R01 MH114927 / NIMH NIH HHS R01 MH115963 / NIMH NIH HHS U54 MD010722 / NIMHD NIH HHS DP2 HD098859 / NICHD NIH HHS R01 MH115961 / NIMH NIH HHS U24 MH068457 / NIMH NIH HHS R01 MH113362 / NIMH NIH HHS R01 NS105746 / NINDS NIH HHS K02 NS085048 / NINDS NIH HHS R56 MH120736 / NIMH NIH HHS R01 MH115958 / NIMH NIH HHS R01 DC016977 / NIDCD NIH HHS R21 HG010652 / NHGRI NIH HHS UL1 TR001863 / NCATS NIH HHS U01 HG009086 / NHGRI NIH HHS
- Language
- English
- Date published
- 01/18/2021
- Academic Unit
- Psychiatry
- Record Identifier
- 9984293753702771
Metrics
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