2023
Genome-Wide Association Study Points to Novel Locus for Gilles de la Tourette Syndrome
Tsetsos F, Topaloudi A, Jain P, Yang Z, Yu D, Kolovos P, Tumer Z, Rizzo R, Hartmann A, Depienne C, Worbe Y, Müller-Vahl K, Cath D, Boomsma D, Wolanczyk T, Zekanowski C, Barta C, Nemoda Z, Tarnok Z, Padmanabhuni S, Buxbaum J, Grice D, Glennon J, Stefansson H, Hengerer B, Yannaki E, Stamatoyannopoulos J, Benaroya-Milshtein N, Cardona F, Hedderly T, Heyman I, Huyser C, Mir P, Morer A, Mueller N, Munchau A, Plessen K, Porcelli C, Roessner V, Walitza S, Schrag A, Martino D, Group T, TSAICG T, Barr C, Batterson J, Berlin C, Budman C, Coppola G, Cox N, Darrow S, Dion Y, Freimer N, Grados M, Greenberg E, Hirschtritt M, Huang A, Illmann C, King R, Kurlan R, Leckman J, Lyon G, Malaty I, McMahon W, Neale B, Okun M, Osiecki L, Robertson M, Rouleau G, Sandor P, Singer H, Smit J, Sul J, Initiative T, Androutsos C, Basha E, Farkas L, Fichna J, Janik P, Kapisyzi M, Karagiannidis I, Koumoula A, Nagy P, Puchala J, Szejko N, Szymanska U, Tsironi V, Group T, Apter A, Ball J, Bodmer B, Bognar E, Buse J, Vela M, Fremer C, Garcia-Delgar B, Gulisano M, Hagen A, Hagstrøm J, Madruga-Garrido M, Pellico A, Ruhrman D, Schnell J, Silvestri P, Skov L, Steinberg T, Gloor F, Turner V, Weidinger E, Network T, Alexander J, Aranyi T, Buisman W, Buitelaar J, Driessen N, Drineas P, Fan S, Forde N, Gerasch S, van den Heuvel O, Jespersgaard C, Kanaan A, Möller H, Nawaz M, Nespoli E, Pagliaroli L, Poelmans G, Pouwels P, Rizzo F, Veltman D, van der Werf Y, Widomska J, Zilhäo N, Group T, Brown L, Cheon K, Coffey B, Fernandez T, Gilbert D, Hong H, Ibanez-Gomez L, Kim E, Kim Y, Kim Y, Koh Y, Kook S, Kuperman S, Leventhal B, Maras A, Murphy T, Shin E, Song D, Song J, State M, Visscher F, Wang S, Zinner S, Tischfield J, Heiman G, Willsey A, Dietrich A, Davis L, Crowley J, Mathews C, Scharf J, Georgitsi M, Hoekstra P, Paschou P. Genome-Wide Association Study Points to Novel Locus for Gilles de la Tourette Syndrome. Biological Psychiatry 2023, 96: 114-124. PMID: 36738982, PMCID: PMC10783199, DOI: 10.1016/j.biopsych.2023.01.023.Peer-Reviewed Original ResearchExpression quantitative trait lociGenome-wide significant lociWide association study dataComplex genetic architectureQuantitative trait lociAssociation study dataGenetic architectureTrait lociChromosome 5q15Significant lociSignificant enrichmentLociNovel insightsNeurodevelopmental disordersChildhood-onset neurodevelopmental disorderHistonesRNAsGenesPolygenic riskFuture studiesEnrichment
2021
Synaptic processes and immune-related pathways implicated in Tourette syndrome
Tsetsos F, Yu D, Sul JH, Huang AY, Illmann C, Osiecki L, Darrow SM, Hirschtritt ME, Greenberg E, Muller-Vahl KR, Stuhrmann M, Dion Y, Rouleau GA, Aschauer H, Stamenkovic M, Schlögelhofer M, Sandor P, Barr CL, Grados MA, Singer HS, Nöthen MM, Hebebrand J, Hinney A, King RA, Fernandez TV, Barta C, Tarnok Z, Nagy P, Depienne C, Worbe Y, Hartmann A, Budman CL, Rizzo R, Lyon GJ, McMahon WM, Batterson JR, Cath DC, Malaty IA, Okun MS, Berlin C, Woods DW, Lee PC, Jankovic J, Robertson MM, Gilbert DL, Brown LW, Coffey BJ, Dietrich A, Hoekstra PJ, Kuperman S, Zinner SH, Wagner M, Knowles JA, Jeremy Willsey A, Tischfield JA, Heiman GA, Cox NJ, Freimer NB, Neale BM, Davis LK, Coppola G, Mathews CA, Scharf JM, Paschou P, Barr C, Batterson J, Berlin C, Budman C, Cath D, Coppola G, Cox N, Darrow S, Davis L, Dion Y, Freimer N, Grados M, Greenberg E, Hirschtritt M, Huang A, Illmann C, King R, Kurlan R, Leckman J, Lyon G, Malaty I, Mathews C, McMahon W, Neale B, Okun M, Osiecki L, Robertson M, Rouleau G, Sandor P, Scharf J, Singer H, Smit J, Sul J, Yu D, Aschauer H, Barta C, Budman C, Cath D, Depienne C, Hartmann A, Hebebrand J, Konstantinidis A, Mathews C, Müller-Vahl K, Nagy P, Nöthen M, Paschou P, Rizzo R, Rouleau G, Sandor P, Scharf J, Schlögelhofer M, Stamenkovic M, Stuhrmann M, Tsetsos F, Tarnok Z, Wolanczyk T, Worbe Y, Brown L, Cheon K, Coffey B, Dietrich A, Fernandez T, Garcia-Delgar B, Gilbert D, Grice D, Hagstrøm J, Hedderly T, Heiman G, Heyman I, Hoekstra P, Huyser C, Kim Y, Kim Y, King R, Koh Y, Kook S, Kuperman S, Leventhal B, Madruga-Garrido M, Mir P, Morer A, Münchau A, Plessen K, Roessner V, Shin E, Song D, Song J, Tischfield J, Willsey A, Zinner S, Aschauer H, Barr C, Barta C, Batterson J, Berlin C, Brown L, Budman C, Cath D, Coffey B, Coppola G, Cox N, Darrow S, Davis L, Depienne C, Dietrich A, Dion Y, Fernandez T, Freimer N, Gilbert D, Grados M, Greenberg E, Hartmann A, Hebebrand J, Heiman G, Hirschtritt M, Hoekstra P, Huang A, Illmann C, Jankovic J, King R, Kuperman S, Lee P, Lyon G, Malaty I, Mathews C, McMahon W, Müller-Vahl K, Nagy P, Neale B, Nöthen M, Okun M, Osiecki L, Paschou P, Rizzo R, Robertson M, Rouleau G, Sandor P, Scharf J, Schlögelhofer M, Singer H, Stamenkovic M, Stuhrmann M, Sul J, Tarnok Z, Tischfield J, Tsetsos F, Willsey A, Woods D, Worbe Y, Yu D, Zinner S. Synaptic processes and immune-related pathways implicated in Tourette syndrome. Translational Psychiatry 2021, 11: 56. PMID: 33462189, PMCID: PMC7814139, DOI: 10.1038/s41398-020-01082-z.Peer-Reviewed Original ResearchConceptsLigand-gated ion channelsGene setsCell adhesionGenome-wide analysisComplex genetic architectureGenome-wide genotypic dataIon channelsSet of genesIndividual-level genotype dataSignificant gene setsAncestry-matched controlsParticular cell typeGenetic architectureImmune-related pathwaysSignaling processesGenotypic dataMAGMA analysisGenotype dataCell typesGenesIndication of involvementTS pathogenesisAdhesion moleculesGlial functionNew insights
2018
De Novo Sequence and Copy Number Variants Are Strongly Associated with Tourette Disorder and Implicate Cell Polarity in Pathogenesis
Wang S, Mandell JD, Kumar Y, Sun N, Morris MT, Arbelaez J, Nasello C, Dong S, Duhn C, Zhao X, Yang Z, Padmanabhuni SS, Yu D, King RA, Dietrich A, Khalifa N, Dahl N, Huang AY, Neale BM, Coppola G, Mathews CA, Scharf JM, Study T, Abdulkadir M, Arbelaez J, Bodmer B, Bromberg Y, Brown L, Cheon K, Coffey B, Deng L, Dietrich A, Dong S, Duhn C, Elzerman L, Fernandez T, Fremer C, Garcia-Delgar B, Gilbert D, Grice D, Hagstrøm J, Hedderly T, Heiman G, Heyman I, Hoekstra P, Hong H, Huyser C, Kim E, Kim Y, Kim Y, King R, Koh Y, Kook S, Kuperman S, Leventhal B, Ludolph A, Madruga-Garrido M, Mandell J, Maras A, Mir P, Morer A, Morris M, Müller-Vahl K, Münchau A, Murphy T, Nasello C, Plessen K, Poisner H, Roessner V, Sanders S, Shin E, Song D, Song J, State M, Sun N, Thackray J, Tischfield J, Tübing J, Visscher F, Wanderer S, Wang S, Willsey A, Woods M, Xing J, Zhang Y, Zhao X, Zinner S, Initiative T, Androutsos C, Barta C, Farkas L, Fichna J, Georgitsi M, Janik P, Karagiannidis I, Koumoula A, Nagy P, Paschou P, Puchala J, Rizzo R, Szejko N, Szymanska U, Tarnok Z, Tsironi V, Wolanczyk T, Zekanowski C, Genetics T, Barr C, Batterson J, Berlin C, Bruun R, Budman C, Cath D, Chouinard S, Coppola G, Cox N, Darrow S, Davis L, Dion Y, Freimer N, Grados M, Hirschtritt M, Huang A, Illmann C, Kurlan R, Leckman J, Lyon G, Malaty I, Mathews C, MacMahon W, Neale B, Okun M, Osiecki L, Pauls D, Posthuma D, Ramensky V, Robertson M, Rouleau G, Sandor P, Scharf J, Singer H, Smit J, Sul J, Yu D, Fernandez T, Buxbaum J, De Rubeis S, Grice D, Xing J, Heiman G, Tischfield J, Paschou P, Willsey A, State M. De Novo Sequence and Copy Number Variants Are Strongly Associated with Tourette Disorder and Implicate Cell Polarity in Pathogenesis. Cell Reports 2018, 24: 3441-3454.e12. PMID: 30257206, PMCID: PMC6475626, DOI: 10.1016/j.celrep.2018.08.082.Peer-Reviewed Original ResearchConceptsCell polarityNumber variantsSequence variantsDe novo damaging variantsDe novoDe novo sequencesCopy number variantsNovo sequencesWhole-exome sequencingDamaging variantsRisk genesGenesCommon pathwayNovoSignificant overlapVariantsTriosGenetic riskSequencingCELSR3PathwayPolaritySequenceSignificant excessFamily
2014
Transcriptome Analysis of the Human Striatum in Tourette Syndrome
Lennington JB, Coppola G, Kataoka-Sasaki Y, Fernandez TV, Palejev D, Li Y, Huttner A, Pletikos M, Sestan N, Leckman JF, Vaccarino FM. Transcriptome Analysis of the Human Striatum in Tourette Syndrome. Biological Psychiatry 2014, 79: 372-382. PMID: 25199956, PMCID: PMC4305353, DOI: 10.1016/j.biopsych.2014.07.018.Peer-Reviewed Original ResearchConceptsCopy number variantsGenome-wide association studiesGene coexpression modulesNumber variantsGene network analysisCommon genetic variantsCoexpression modulesUpregulated genesMetabolism modulesImmune-related genesNetwork analysisAssociation studiesDifferential expressionUpregulated modulesGenetic variantsGenesPatient's striatumTS individualsTranscriptomeVariantsMetabolic alterationsSame regionGamma-aminobutyric acidergic interneuronsTranscriptsRNA
2013
Gene variants associated with antisocial behaviour: a latent variable approach
Bentley MJ, Lin H, Fernandez TV, Lee M, Yrigollen CM, Pakstis AJ, Katsovich L, Olds DL, Grigorenko EL, Leckman JF. Gene variants associated with antisocial behaviour: a latent variable approach. Journal Of Child Psychology And Psychiatry 2013, 54: 1074-1085. PMID: 23822756, PMCID: PMC3766409, DOI: 10.1111/jcpp.12109.Peer-Reviewed Original ResearchConceptsRisk allelesGenetic risk allelesSingle nucleotide polymorphismsGene variantsNurse home visitation programAge 15 yearsStress response pathwaysCholinergic signalingDrug useCommon genetic variantsPutative risk allelesAntisocial behaviorVariable scoresResponse pathwaysGenetic polymorphismsVisitation programMolecular networksPathway analysisStress responseGenesGenetic variablesMolecular levelGenetic variants
2012
Genome-wide association study of Tourette's syndrome
Scharf JM, Yu D, Mathews CA, Neale BM, Stewart SE, Fagerness JA, Evans P, Gamazon E, Edlund CK, Service SK, Tikhomirov A, Osiecki L, Illmann C, Pluzhnikov A, Konkashbaev A, Davis LK, Han B, Crane J, Moorjani P, Crenshaw AT, Parkin MA, Reus VI, Lowe TL, Rangel-Lugo M, Chouinard S, Dion Y, Girard S, Cath DC, Smit JH, King RA, Fernandez TV, Leckman JF, Kidd KK, Kidd JR, Pakstis AJ, State MW, Herrera LD, Romero R, Fournier E, Sandor P, Barr CL, Phan N, Gross-Tsur V, Benarroch F, Pollak Y, Budman CL, Bruun RD, Erenberg G, Naarden AL, Lee PC, Weiss N, Kremeyer B, Berrío GB, Campbell DD, Cardona Silgado JC, Ochoa WC, Mesa Restrepo SC, Muller H, Valencia Duarte AV, Lyon GJ, Leppert M, Morgan J, Weiss R, Grados MA, Anderson K, Davarya S, Singer H, Walkup J, Jankovic J, Tischfield JA, Heiman GA, Gilbert DL, Hoekstra PJ, Robertson MM, Kurlan R, Liu C, Gibbs JR, Singleton A, Hardy J, Strengman E, Ophoff R, Wagner M, Moessner R, Mirel D, Posthuma D, Sabatti C, Eskin E, Conti D, Knowles J, Ruiz-Linares A, Rouleau G, Purcell S, Heutink P, Oostra B, McMahon W, Freimer N, Cox N, Pauls D. Genome-wide association study of Tourette's syndrome. Molecular Psychiatry 2012, 18: 721-728. PMID: 22889924, PMCID: PMC3605224, DOI: 10.1038/mp.2012.69.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAttention Deficit Disorder with HyperactivityCase-Control StudiesChromosomes, Human, Pair 9FemaleFibrillar CollagensGenetic Predisposition to DiseaseGenome-Wide Association StudyGenotypeHumansInternational CooperationMaleMeta-Analysis as TopicObsessive-Compulsive DisorderPolymorphism, Single NucleotideTourette SyndromeWhite PeopleYoung AdultConceptsGenome-wide association studiesFirst genome-wide association studyAssociation studiesTop signalsFull genetic architectureAncestry-matched controlsEuropean ancestry samplesGenetic architectureGWAS dataComplex inheritanceEuropean-derived populationsSusceptibility variantsSusceptibility genesEventual identificationEuropean ancestryCosta RicaChromosome 9q32Familial recurrence rateNorth AmericaComplete understandingAmerican populationCentral ValleyNeuropsychiatric diseasesDevelopmental disordersGenes
2011
Rare Copy Number Variants in Tourette Syndrome Disrupt Genes in Histaminergic Pathways and Overlap with Autism
Fernandez TV, Sanders SJ, Yurkiewicz IR, Ercan-Sencicek AG, Kim YS, Fishman DO, Raubeson MJ, Song Y, Yasuno K, Ho WS, Bilguvar K, Glessner J, Chu SH, Leckman JF, King RA, Gilbert DL, Heiman GA, Tischfield JA, Hoekstra PJ, Devlin B, Hakonarson H, Mane SM, Günel M, State MW. Rare Copy Number Variants in Tourette Syndrome Disrupt Genes in Histaminergic Pathways and Overlap with Autism. Biological Psychiatry 2011, 71: 392-402. PMID: 22169095, PMCID: PMC3282144, DOI: 10.1016/j.biopsych.2011.09.034.Peer-Reviewed Original ResearchConceptsCopy number variationsRare copy number variationsNovel risk regionsEnrichment of genesGamma-aminobutyric acid receptor genesNervous system developmentEtiology of TSParent-child triosRare copy number variantsCopy number variantsGene mappingPathway analysisDe novo eventsAxon guidanceCell adhesionMolecular pathwaysNumber variationsRelevant pathwaysCNV analysisNumber variantsGenesReceptor geneDe novoNovo eventsPathway
2008
Genes Controlling Affiliative Behavior as Candidate Genes for Autism
Yrigollen CM, Han SS, Kochetkova A, Babitz T, Chang JT, Volkmar FR, Leckman JF, Grigorenko EL. Genes Controlling Affiliative Behavior as Candidate Genes for Autism. Biological Psychiatry 2008, 63: 911-916. PMID: 18207134, PMCID: PMC2386897, DOI: 10.1016/j.biopsych.2007.11.015.Peer-Reviewed Original ResearchMeSH KeywordsAnalysis of VarianceAsperger SyndromeAutistic DisorderBehaviorChildDopamine beta-HydroxylaseFamily HealthFemaleGenetic LinkageGenetic Predisposition to DiseaseGenetic VariationGenotypeHumansMaleOrganizational AffiliationOxytocinProlactinProto-Oncogene Proteins c-fosReceptors, OxytocinReceptors, ProlactinConceptsHeterogeneous genetic factorsAllelic associationCandidate genesAssociation analysisGenetic linkageManifestation of ASDGenesGenetic variantsAllelic variantsFBAT softwareGenetic factorsComplex etiologyIndependent replicationNeurodevelopmental disordersOXTR geneAffiliative behaviorMultiple facetsVariantsPRLRPhenotypeHypothesis
2004
Linkage analysis of ordinal traits for pedigree data
Feng R, Leckman JF, Zhang H. Linkage analysis of ordinal traits for pedigree data. Proceedings Of The National Academy Of Sciences Of The United States Of America 2004, 101: 16739-16744. PMID: 15548606, PMCID: PMC534720, DOI: 10.1073/pnas.0404623101.Peer-Reviewed Original ResearchConceptsLinkage analysisOrdinal traitsTourette Syndrome Association International ConsortiumLinkage analysis methodsQuantitative traitsEvidence of linkageGenome scanLinkage scanHuman diseasesAllele sharingTraitsPedigree dataInheritance patternDichotomous traitsSignificant allele sharingPhenotypeProportional odds logistic modelGENEHUNTERGenesGeneticsMarkersInternational Consortium
1991
Detection of homeobox genes in development and evolution.
Murtha MT, Leckman JF, Ruddle FH. Detection of homeobox genes in development and evolution. Proceedings Of The National Academy Of Sciences Of The United States Of America 1991, 88: 10711-10715. PMID: 1720547, PMCID: PMC53000, DOI: 10.1073/pnas.88.23.10711.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBase SequenceBiological EvolutionCiona intestinalisCodonDipteraDrosophilaEmbryo, MammalianEmbryo, NonmammalianGenes, HomeoboxMaleMiceMolecular Sequence DataOligodeoxyribonucleotidesPolymerase Chain ReactionRestriction MappingRNASequence Homology, Nucleic AcidTelencephalonConceptsHomeobox genesHomeobox sequencesDNA-binding regulatory proteinsDiverse metazoan speciesSurvey of sequencesMouse genomic DNAImportant model systemPopulations of DNAMetazoan speciesAncient roleMetazoan evolutionPolymerase chain reactionGenomic organizationDrosophila H2.0Regulatory proteinsHlx geneGenomic DNAStudy of developmentMouse telencephalonNovel sequencesGenesOligonucleotide primersHomeodomainModel systemRNA