Tsetsos, FotisYu, DongmeiSul, Jae HoonHuang, Alden YIllmann, CorneliaOsiecki, LisaDarrow, Sabrina MHirschtritt, Matthew EGreenberg, EricaMuller-Vahl, Kirsten RStuhrmann, ManfredDion, YvesRouleau, Guy AAschauer, HaraldStamenkovic, MaraSchlögelhofer, MonikaSandor, PaulBarr, Cathy LGrados, Marco ASinger, Harvey SNöthen, Markus MHebebrand, JohannesHinney, AnkeKing, Robert AFernandez, Thomas VBarta, CsabaTarnok, ZsanettNagy, PeterDepienne, ChristelWorbe, YuliaHartmann, AndreasBudman, Cathy LRizzo, RenataLyon, Gholson JMcMahon, William MBatterson, James RCath, Danielle CMalaty, Irene AOkun, Michael SBerlin, ChestonWoods, Douglas WLee, Paul CJankovic, JosephRobertson, Mary MGilbert, Donald LBrown, Lawrence WCoffey, Barbara JDietrich, AndreaHoekstra, Pieter JKuperman, SamuelZinner, Samuel HWagner, MichaelKnowles, James AJeremy Willsey, ATischfield, Jay AHeiman, Gary ACox, Nancy JFreimer, Nelson BNeale, Benjamin MDavis, Lea KCoppola, GiovanniMathews, Carol AScharf, Jeremiah MPaschou, PeristeraTourette Association of America International Consortium for GeneticsBarr, Cathy LBatterson, James RBerlin, ChestonBudman, Cathy LCath, Danielle CCoppola, GiovanniCox, Nancy JDarrow, SabrinaDavis, Lea KDion, YvesFreimer, Nelson BGrados, Marco AGreenberg, EricaHirschtritt, Matthew EHuang, Alden YIllmann, CorneliaKing, Robert AKurlan, RogerLeckman, James FLyon, Gholson JMalaty, Irene AMathews, Carol AMcMahon, William MNeale, Benjamin MOkun, Michael SOsiecki, LisaRobertson, Mary MRouleau, Guy ASandor, PaulScharf, Jeremiah MSinger, Harvey SSmit, Jan HSul, Jae HoonYu, DongmeiGilles de la Tourette GWAS Replication InitiativeAschauer, Harald Aschauer HaraldBarta, CsabaBudman, Cathy LCath, Danielle CDepienne, ChristelHartmann, AndreasHebebrand, JohannesKonstantinidis, AnastasiosMathews, Carol AMüller-Vahl, KirstenNagy, PeterNöthen, Markus MPaschou, PeristeraRizzo, RenataRouleau, Guy ASandor, PaulScharf, Jeremiah MSchlögelhofer, MonikaStamenkovic, MaraStuhrmann, ManfredTsetsos, FotisTarnok, ZsanettWolanczyk, TomaszWorbe, YuliaTourette International Collaborative Genetics StudyBrown, LawrenceCheon, Keun-AhCoffey, Barbara JDietrich, AndreaFernandez, Thomas VGarcia-Delgar, BlancaGilbert, DonaldGrice, Dorothy EHagstrøm, JulieHedderly, TammyHeiman, Gary AHeyman, IsobelHoekstra, Pieter JHuyser, ChaimKim, Young KeyKim, Young-ShinKing, Robert AKoh, Yun-JooKook, SodahmKuperman, SamuelLeventhal, Bennett LMadruga-Garrido, MarcosMir, PabloMorer, AstridMünchau, AlexanderPlessen, Kerstin JRoessner, VeitShin, Eun-YoungSong, Dong-HoSong, JungeunTischfield, Jay AWillsey, A JeremyZinner, SamuelPsychiatric Genomics Consortium Tourette Syndrome Working GroupAschauer, HaraldBarr, Cathy LBarta, CsabaBatterson, James RBerlin, ChestonBrown, LawrenceBudman, Cathy LCath, Danielle CCoffey, Barbara JCoppola, GiovanniCox, Nancy JDarrow, SabrinaDavis, Lea KDepienne, ChristelDietrich, AndreaDion, YvesFernandez, ThomasFreimer, Nelson BGilbert, DonaldGrados, Marco AGreenberg, EricaHartmann, AndreasHebebrand, JohannesHeiman, GaryHirschtritt, Matthew EHoekstra, PieterHuang, Alden YIllmann, CorneliaJankovic, JosephKing, Robert AKuperman, SamuelLee, Paul CLyon, Gholson JMalaty, Irene AMathews, Carol AMcMahon, William MMüller-Vahl, KirstenNagy, PeterNeale, Benjamin MNöthen, Markus MOkun, Michael SOsiecki, LisaPaschou, PeristeraRizzo, RenataRobertson, Mary MRouleau, Guy ASandor, PaulScharf, Jeremiah MSchlögelhofer, MonikaSinger, Harvey SStamenkovic, MaraStuhrmann, ManfredSul, Jae HoonTarnok, ZsanettTischfield, JayTsetsos, FotisWillsey, A JeremyWoods, DouglasWorbe, YuliaYu, DongmeiZinner, Samuel2025-01-072025-01-072021-01-18https://hdl.handle.net/10668/25697Tourette 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.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/Genome-Wide Association StudyGenotypeHumansNeuronsTourette Syndromeresearch article33462189open access10.1038/s41398-020-01082-z2158-3188PMC7814139https://www.nature.com/articles/s41398-020-01082-z.pdfhttps://pmc.ncbi.nlm.nih.gov/articles/PMC7814139/pdf