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
2017
Rare Copy Number Variants in NRXN1 and CNTN6 Increase Risk for Tourette Syndrome
Huang AY, Yu D, Davis LK, Sul JH, Tsetsos F, Ramensky V, Zelaya I, Ramos EM, Osiecki L, Chen JA, McGrath LM, Illmann C, Sandor P, Barr CL, Grados M, Singer HS, Nöthen MM, Hebebrand J, King RA, Dion Y, Rouleau G, Budman CL, Depienne C, Worbe Y, Hartmann A, Müller-Vahl KR, Stuhrmann M, Aschauer H, Stamenkovic M, Schloegelhofer M, Konstantinidis A, Lyon GJ, McMahon WM, Barta C, Tarnok Z, Nagy P, Batterson JR, Rizzo R, Cath DC, Wolanczyk T, Berlin C, Malaty IA, Okun MS, Woods DW, Rees E, Pato CN, Pato MT, Knowles JA, Posthuma D, Pauls DL, Cox NJ, Neale BM, Freimer NB, Paschou P, Mathews CA, Scharf JM, Coppola G, Genetics T, Bruun R, Chouinard S, Darrow S, Greenberg E, Hirschtritt M, de la Tourette Syndrome GWAS Replication Initiative T, Kurlan R, Leckman J, Robertson M, Smit J. Rare Copy Number Variants in NRXN1 and CNTN6 Increase Risk for Tourette Syndrome. Neuron 2017, 94: 1101-1111.e7. PMID: 28641109, PMCID: PMC5568251, DOI: 10.1016/j.neuron.2017.06.010.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultCalcium-Binding ProteinsCase-Control StudiesCell Adhesion Molecules, NeuronalChildContactinsDNA Copy Number VariationsFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyGenotypeHumansMaleNerve Tissue ProteinsNeural Cell Adhesion MoleculesOdds RatioTourette SyndromeWhite PeopleYoung AdultConceptsCopy number variantsRare copy number variantsSignificant lociGenome-wide significant lociWide significant lociRare structural variationAncestry-matched controlsSNP microarray dataGlobal CNV burdenEuropean ancestry samplesGenetic architectureUnderlying genetic causeMicroarray dataNumber variantsTS casesCNV burdenSingleton eventsGenetic causeStructural variationsLociPathogenic copy number variantsAbnormal developmentModel neuropsychiatric disorderTS riskVariants
2015
The association between 2D:4D ratio and cognitive empathy is contingent on a common polymorphism in the oxytocin receptor gene (OXTR rs53576)
Weisman O, Pelphrey KA, Leckman JF, Feldman R, Lu Y, Chong A, Chen Y, Monakhov M, Chew SH, Ebstein RP. The association between 2D:4D ratio and cognitive empathy is contingent on a common polymorphism in the oxytocin receptor gene (OXTR rs53576). Psychoneuroendocrinology 2015, 58: 23-32. PMID: 25935637, DOI: 10.1016/j.psyneuen.2015.04.007.Peer-Reviewed Original ResearchConceptsOxytocin receptor geneCognitive empathyRMET performanceFetal testosteroneHuman social cognitionSocial-cognitive developmentSocio-cognitive skillsRole of oxytocinSocio-affective skillsSocial cognitionPsychosocial competenceHigh fetal testosteroneIndividual differencesCognitive developmentBaron-CohenEmotional statesOXTR rs53576OXTR geneGreater identificationEmpathyCore aspectsRMETCognitionUnique supportTestosterone system
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
2009
Autism spectrum and obsessive–compulsive disorders: OC behaviors, phenotypes and genetics
Jacob S, Landeros‐Weisenberger A, Leckman JF. Autism spectrum and obsessive–compulsive disorders: OC behaviors, phenotypes and genetics. Autism Research 2009, 2: 293-311. PMID: 20029829, PMCID: PMC3974607, DOI: 10.1002/aur.108.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsChildChild Development Disorders, PervasiveChild, PreschoolComorbidityDiagnosis, DifferentialDisease Models, AnimalDiseases in TwinsGenetic Association StudiesGenetic Predisposition to DiseaseGenotypeHumansInfantIntellectual DisabilityInterview, PsychologicalNeuropsychological TestsObsessive-Compulsive DisorderPhenotypeQuantitative Trait, HeritableStereotyped BehaviorConceptsAutism spectrum disorderObsessive-compulsive behaviorObsessive-compulsive disorderNovel treatment interventionsFamily genetic studiesAutism spectrumGeneralist genesOC behaviorSpectrum disorderRare genetic variantsASD variesHeritable endophenotypeASD phenotypeCandidate gene studiesNovel genomic technologiesNonparametric linkage analysisInnovative statistical approachChronological ageGenetic mechanismsGenomic technologiesTreatment interventionsGenetic analysisGenetic influencesLinkage analysisGene studiesRisk and Resilience: Early Manipulation of Macaque Social Experience and Persistent Behavioral and Neurophysiological Outcomes
Stevens HE, Leckman JF, Coplan JD, Suomi SJ. Risk and Resilience: Early Manipulation of Macaque Social Experience and Persistent Behavioral and Neurophysiological Outcomes. Journal Of The American Academy Of Child & Adolescent Psychiatry 2009, 48: 114-127. PMID: 19127170, DOI: 10.1097/chi.0b013e318193064c.Peer-Reviewed Original ResearchAdolescentAdolescent BehaviorAnimalsChildChild BehaviorChild DevelopmentChild RearingChild, PreschoolGenotypeHumansInfantInfant, NewbornMacacaMother-Child RelationsNeurophysiologyNeurotransmitter AgentsResilience, PsychologicalRiskRisk FactorsSocial BehaviorSocial EnvironmentStress, PsychologicalTemperament
2008
A Developmental and Evolutionary Perspective on Obsessive-Compulsive Disorder: Whence and Whither Compulsive Hoarding?
Leckman JF, Bloch MH. A Developmental and Evolutionary Perspective on Obsessive-Compulsive Disorder: Whence and Whither Compulsive Hoarding? American Journal Of Psychiatry 2008, 165: 1229-1233. PMID: 18829875, DOI: 10.1176/appi.ajp.2008.08060891.Peer-Reviewed Original ResearchGenes 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
1996
Linkage disequilibrium between an allele at the dopamine D4 receptor locus and Tourette syndrome, by the transmission-disequilibrium test.
Grice DE, Leckman JF, Pauls DL, Kurlan R, Kidd KK, Pakstis AJ, Chang FM, Buxbaum JD, Cohen DJ, Gelernter J. Linkage disequilibrium between an allele at the dopamine D4 receptor locus and Tourette syndrome, by the transmission-disequilibrium test. American Journal Of Human Genetics 1996, 59: 644-52. PMID: 8751866, PMCID: PMC1914894.Peer-Reviewed Original ResearchConceptsTourette syndromeChronic multiple ticsMultiple ticsTransmission disequilibrium test (TDT) methodsDopaminergic abnormalitiesFamily triosTransmission disequilibrium testReceptor locusSyndromeDopamine D4 receptor locusFunctional mutationsFunctional studiesCommon allelesAllelesPathogenesisParticular allelesDifferent binding propertiesAbnormalities