2024
Rare de novo damaging DNA variants are enriched in attention-deficit/hyperactivity disorder and implicate risk genes
Olfson E, Farhat L, Liu W, Vitulano L, Zai G, Lima M, Parent J, Polanczyk G, Cappi C, Kennedy J, Fernandez T. Rare de novo damaging DNA variants are enriched in attention-deficit/hyperactivity disorder and implicate risk genes. Nature Communications 2024, 15: 5870. PMID: 38997333, PMCID: PMC11245598, DOI: 10.1038/s41467-024-50247-7.Peer-Reviewed Original ResearchMeSH KeywordsAttention Deficit Disorder with HyperactivityCase-Control StudiesChildExome SequencingFemaleGenetic Predisposition to DiseaseHistone DemethylasesHumansMaleMutationRisk FactorsConceptsDNA sequencesRisk genesHigh-confidence risk genesWhole-exome DNA sequencingSequencing of familiesIdentified de novoLysine demethylase 5BDNA variantsTrio cohortBiological pathwaysGenesSequencing cohortGenetic factorsChildhood neurodevelopmental disordersAttention-deficit/hyperactivity disorderSequenceVariantsADHD riskNeurodevelopmental disordersKDM5BDNAMutationsFamilyLysineDiscovery
2023
Primary complex motor stereotypies are associated with de novo damaging DNA coding mutations that identify KDM5B as a risk gene
Fernandez T, Williams Z, Kline T, Rajendran S, Augustine F, Wright N, Sullivan C, Olfson E, Abdallah S, Liu W, Hoffman E, Gupta A, Singer H. Primary complex motor stereotypies are associated with de novo damaging DNA coding mutations that identify KDM5B as a risk gene. PLOS ONE 2023, 18: e0291978. PMID: 37788244, PMCID: PMC10547198, DOI: 10.1371/journal.pone.0291978.Peer-Reviewed Original ResearchMeSH KeywordsAutism Spectrum DisorderDNAExome SequencingGenetic Predisposition to DiseaseHumansJumonji Domain-Containing Histone DemethylasesMutationNuclear ProteinsRepressor ProteinsTourette SyndromeConceptsRisk genesDe novo damaging variantsGene expression patternsWhole-exome DNA sequencingMid-fetal developmentAdditional risk genesHigh-confidence risk genesParent-child triosGene OntologyCell signalingExpression patternsCalcium ion transportFunctional convergenceCell cycleDamaging variantsGenesDNA sequencingDe novoASD probandsGenetic etiologyBiological mechanismsSequencingDNANetwork analysisIon transport
2022
Whole‐exome DNA sequencing in childhood anxiety disorders identifies rare de novo damaging coding variants
Olfson E, Lebowitz ER, Hommel G, Pashankar N, Silverman WK, Fernandez TV. Whole‐exome DNA sequencing in childhood anxiety disorders identifies rare de novo damaging coding variants. Depression And Anxiety 2022, 39: 474-484. PMID: 35312124, PMCID: PMC9246845, DOI: 10.1002/da.23251.Peer-Reviewed Original ResearchMeSH KeywordsAnxiety DisordersBiological ProductsExomeGenetic Predisposition to DiseaseHumansSequence Analysis, DNAConceptsWhole-exome DNA sequencingRisk genesDNA sequencingCanonical biological pathwaysMissense genetic variantsNovo variantsGenetic variant detectionParent-child triosGenomic approachesDe novo variantsLikely geneBiologic pathwaysDeleterious variantsBiological pathwaysDamaging variantsGenesGenetic variantsPathwayVariant detectionSequencingNetwork analysisGenetic factorsUnderlying biologyVariantsEnrichment
2021
Whole-exome sequencing identifies genes associated with Tourette’s disorder in multiplex families
Cao X, Zhang Y, Abdulkadir M, Deng L, Fernandez TV, Garcia-Delgar B, Hagstrøm J, Hoekstra PJ, King RA, Koesterich J, Kuperman S, Morer A, Nasello C, Plessen KJ, Thackray JK, Zhou L, Dietrich A, Tischfield J, Heiman G, Xing J. Whole-exome sequencing identifies genes associated with Tourette’s disorder in multiplex families. Molecular Psychiatry 2021, 26: 6937-6951. PMID: 33837273, PMCID: PMC8501157, DOI: 10.1038/s41380-021-01094-1.Peer-Reviewed Original ResearchMeSH KeywordsCadherin Related ProteinsExome SequencingFamilyGenetic Predisposition to DiseaseHumansNerve Tissue ProteinsPedigreeSerine EndopeptidasesTourette SyndromeConceptsCandidate genesProtein-protein interaction networkGene ontology categoriesHigh-throughput sequencingStrong candidate geneCandidate gene expressionFamily member 1Heritable neurodevelopmental disorderIdentifies genesNovel genesOntology categoriesNeurodevelopmental disordersMultiplex familiesInteraction networksPolygenic natureBiological insightsGene expressionFunction predictionWhole-exome sequencingGenesGenetic variantsSegregation patternsGenetic heterogeneitySegregation informationMember 1
2019
Interrogating the Genetic Determinants of Tourette’s Syndrome and Other Tic Disorders Through Genome-Wide Association Studies
Yu D, Sul JH, Tsetsos F, Nawaz MS, Huang AY, Zelaya I, Illmann C, Osiecki L, Darrow SM, Hirschtritt ME, Greenberg E, Muller-Vahl KR, Stuhrmann M, Dion Y, Rouleau G, Aschauer H, Stamenkovic M, Schlögelhofer M, Sandor P, Barr CL, Grados M, 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, Luðvigsson P, Sæmundsen E, Thorarensen Ó, Atzmon G, Barzilai N, Wagner M, Moessner R, Ophoff R, Pato CN, Pato MT, Knowles JA, Roffman JL, Smoller JW, Buckner RL, Willsey AJ, Tischfield JA, Heiman GA, Stefansson H, Stefansson K, Posthuma D, Cox NJ, Pauls DL, Freimer NB, Neale BM, Davis LK, Paschou P, Coppola G, Mathews CA, Scharf JM. Interrogating the Genetic Determinants of Tourette’s Syndrome and Other Tic Disorders Through Genome-Wide Association Studies. American Journal Of Psychiatry 2019, 176: 217-227. PMID: 30818990, PMCID: PMC6677250, DOI: 10.1176/appi.ajp.2018.18070857.Peer-Reviewed Original ResearchConceptsGenome-wide association study approachGenome-wide significant lociGenome-wide association studiesGene-based associationGene-based analysisPolygenic risk scoresGenetic architectureSignificant lociEnrichment analysisGene expressionTop lociGenetic levelAssociation studiesSyndrome pathogenesisGenetic determinantsChromosome 13Genetic variantsGWASGenetic etiologyIndependent population-based samplesLociFundamental mechanismsGenesVariantsHeritability
2018
Chapter 49 Genetic susceptibility in obsessive-compulsive disorder
Fernandez TV, Leckman JF, Pittenger C. Chapter 49 Genetic susceptibility in obsessive-compulsive disorder. Handbook Of Clinical Neurology 2018, 148: 767-781. PMID: 29478613, DOI: 10.1016/b978-0-444-64076-5.00049-1.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsAnimalsDisease Models, AnimalDNA Copy Number VariationsGenetic Predisposition to DiseaseGlutamic AcidHumansMiceObsessive-Compulsive DisorderSignal TransductionConceptsObsessive-compulsive disorderPotential novel therapeutic avenuesNovel therapeutic avenuesSpecific risk allelesUnderlying pathophysiologyLarge cohortLifelong disabilityImmune pathwaysTherapeutic avenuesNew treatmentsGenetic susceptibilityRisk allelesCandidate gene association studiesMouse knockout modelsGenetic findingsGene association studiesKnockout modelsOCD pathologyRisk variantsNotable inroadsGenetic variantsDisordersVulnerable pathwaysSubstantial genetic contributionRepetitive behaviors
2017
De Novo Coding Variants Are Strongly Associated with Tourette Disorder
Willsey AJ, Fernandez TV, Yu D, King RA, Dietrich A, Xing J, Sanders SJ, Mandell JD, Huang AY, Richer P, Smith L, Dong S, Samocha KE, Genetics T, Abdulkadir M, Bohnenpoll J, Bromberg Y, Brown L, Cheon K, Coffey B, Deng L, Dietrich A, Dong S, Elzerman L, Fernandez T, Fründt O, Garcia-Delgar B, Gedvilaite E, Gilbert D, Grice D, Hagstrøm J, Hedderly T, Heiman G, Heyman I, Hoekstra P, Hong H, Huyser C, Ibanez-Gomez L, Kim Y, Kim Y, King R, Koh Y, Kook S, Kuperman S, Lamerz A, Leventhal B, Ludolph A, da Silva C, Madruga-Garrido M, Mandell J, Maras A, Mir P, Morer A, Münchau A, Murphy T, Nasello C, Openneer T, Plessen K, Richer P, Roessner V, Sanders S, Shin E, Sival D, Smith L, Song D, Song J, State M, Stolte A, Sun N, Tischfield J, Tübing J, Visscher F, Walker M, Wanderer S, Wang S, Willsey A, Woods M, Xing J, Zhang Y, Zhou A, Zinner S, 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, MaMahon 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, Neale B, Coppola G, Mathews C, Tischfield J, Scharf J, State M, Heiman G. De Novo Coding Variants Are Strongly Associated with Tourette Disorder. Neuron 2017, 94: 486-499.e9. PMID: 28472652, PMCID: PMC5769876, DOI: 10.1016/j.neuron.2017.04.024.Peer-Reviewed Original ResearchConceptsWhole-exome sequencingTourette's disorderDamaging variantsLikely gene-disrupting variantsComplex neurodevelopmental disorderClinical casesUnrelated probandsNeurodevelopmental disordersDe novo damaging variantsDisordersRisk genesGenetic cohortsConsistent evidenceCoding variantReplication sampleProbandsInternational ConsortiumCohortVariants
2015
No Evidence for Association of Autism with Rare Heterozygous Point Mutations in Contactin-Associated Protein-Like 2 (CNTNAP2), or in Other Contactin-Associated Proteins or Contactins
Murdoch JD, Gupta AR, Sanders SJ, Walker MF, Keaney J, Fernandez TV, Murtha MT, Anyanwu S, Ober GT, Raubeson MJ, DiLullo NM, Villa N, Waqar Z, Sullivan C, Gonzalez L, Willsey AJ, Choe SY, Neale BM, Daly MJ, State MW. No Evidence for Association of Autism with Rare Heterozygous Point Mutations in Contactin-Associated Protein-Like 2 (CNTNAP2), or in Other Contactin-Associated Proteins or Contactins. PLOS Genetics 2015, 11: e1004852. PMID: 25621974, PMCID: PMC4306541, DOI: 10.1371/journal.pgen.1004852.Peer-Reviewed Original ResearchConceptsContactin-Associated ProteinSingle nucleotide variantsRelated gene familiesPoint mutationsLike-2Autism risk genesHeterozygous single-nucleotide variantsNumber variation analysisGene familyNext-generation sequencingSequence dataMolecular cytogeneticsRare point mutationsAssociation studiesHomozygosity mappingNucleotide variantsRisk genesRare heterozygous mutationsProteinHeterozygous point mutationMutationsGenesVariation analysisContactinHeterozygous mutations
2014
Copy Number Variation in Obsessive-Compulsive Disorder and Tourette Syndrome: A Cross-Disorder Study
McGrath LM, Yu D, Marshall C, Davis LK, Thiruvahindrapuram B, Li B, Cappi C, Gerber G, Wolf A, Schroeder FA, Osiecki L, O'Dushlaine C, Kirby A, Illmann C, Haddad S, Gallagher P, Fagerness JA, Barr CL, Bellodi L, Benarroch F, Bienvenu OJ, Black DW, Bloch MH, Bruun RD, Budman CL, Camarena B, Cath DC, Cavallini MC, Chouinard S, Coric V, Cullen B, Delorme R, Denys D, Derks EM, Dion Y, Rosário MC, Eapen V, Evans P, Falkai P, Fernandez TV, Garrido H, Geller D, Grabe HJ, Grados MA, Greenberg BD, Gross-Tsur V, Grünblatt E, Heiman GA, Hemmings SM, Herrera LD, Hounie AG, Jankovic J, Kennedy JL, King RA, Kurlan R, Lanzagorta N, Leboyer M, Leckman JF, Lennertz L, Lochner C, Lowe TL, Lyon GJ, Macciardi F, Maier W, McCracken JT, McMahon W, Murphy DL, Naarden AL, Neale BM, Nurmi E, Pakstis AJ, Pato MT, Pato CN, Piacentini J, Pittenger C, Pollak Y, Reus VI, Richter MA, Riddle M, Robertson MM, Rosenberg D, Rouleau GA, Ruhrmann S, Sampaio AS, Samuels J, Sandor P, Sheppard B, Singer HS, Smit JH, Stein DJ, Tischfield JA, Vallada H, Veenstra-VanderWeele J, Walitza S, Wang Y, Wendland JR, Shugart YY, Miguel EC, Nicolini H, Oostra BA, Moessner R, Wagner M, Ruiz-Linares A, Heutink P, Nestadt G, Freimer N, Petryshen T, Posthuma D, Jenike MA, Cox NJ, Hanna GL, Brentani H, Scherer SW, Arnold PD, Stewart SE, Mathews CA, Knowles JA, Cook EH, Pauls DL, Wang K, Scharf JM. Copy Number Variation in Obsessive-Compulsive Disorder and Tourette Syndrome: A Cross-Disorder Study. Journal Of The American Academy Of Child & Adolescent Psychiatry 2014, 53: 910-919. PMID: 25062598, PMCID: PMC4218748, DOI: 10.1016/j.jaac.2014.04.022.Peer-Reviewed Original ResearchThe Tourette International Collaborative Genetics (TIC Genetics) study, finding the genes causing Tourette syndrome: objectives and methods
Dietrich A, Fernandez TV, King RA, State MW, Tischfield JA, Hoekstra PJ, Heiman GA, the TIC Genetics Collaborative Group. The Tourette International Collaborative Genetics (TIC Genetics) study, finding the genes causing Tourette syndrome: objectives and methods. European Child & Adolescent Psychiatry 2014, 24: 141-151. PMID: 24771252, PMCID: PMC4209328, DOI: 10.1007/s00787-014-0543-x.Peer-Reviewed Original ResearchConceptsGenetic studiesSimilar genetic architectureGene discovery effortsMultiply affected pedigreesSingle major geneParent-child triosGenetic architectureMultigenic inheritanceDe novo mutationsMajor geneGenomic researchCollaborative Genetics StudyAffected pedigreesDiscovery effortsGenetic variantsGenetic contributionGenetics ConsortiumNovo mutationsGenesRare variantsBroader scientific communityGenetic riskRecent progressGeneticsVariants
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 variantsChapter Six Genetic Susceptibility and Neurotransmitters in Tourette Syndrome
Paschou P, Fernandez TV, Sharp F, Heiman GA, Hoekstra PJ. Chapter Six Genetic Susceptibility and Neurotransmitters in Tourette Syndrome. International Review Of Neurobiology 2013, 112: 155-177. PMID: 24295621, PMCID: PMC4471172, DOI: 10.1016/b978-0-12-411546-0.00006-8.ChaptersConceptsGene expression findingsExpression findingsEtiology of TSGenetic workTwo-generation pedigreeTs phenotypeMolecular baseGenetic contributionTourette syndromeLikely interactionsMultifactorial inheritanceSegregation studiesNeurotransmitter systemsAutosomal dominant disorderGenetic factorsDynamic interplayGenetic susceptibilityNew treatment optionsExtracellular dopamine levelsGamma-aminobutyric acidDominant disorderGenesTreatment optionsCortico-striatoDopamine levels
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
2010
L-Histidine Decarboxylase and Tourette's Syndrome
Ercan-Sencicek AG, Stillman AA, Ghosh AK, Bilguvar K, O'Roak BJ, Mason CE, Abbott T, Gupta A, King RA, Pauls DL, Tischfield JA, Heiman GA, Singer HS, Gilbert DL, Hoekstra PJ, Morgan TM, Loring E, Yasuno K, Fernandez T, Sanders S, Louvi A, Cho JH, Mane S, Colangelo CM, Biederer T, Lifton RP, Gunel M, State MW. L-Histidine Decarboxylase and Tourette's Syndrome. New England Journal Of Medicine 2010, 362: 1901-1908. PMID: 20445167, PMCID: PMC2894694, DOI: 10.1056/nejmoa0907006.Peer-Reviewed Original ResearchMeSH KeywordsChromosome MappingCodon, NonsenseFemaleGenes, DominantGenetic LinkageGenetic Predisposition to DiseaseHaplotypesHistidine DecarboxylaseHumansMaleMicrosatellite RepeatsPedigreePolymerase Chain ReactionTourette SyndromeConceptsRare functional mutationsL-histidine decarboxylaseRate-limiting enzymeHDC geneTwo-generation pedigreeFunctional mutationsStrong genetic contributionHistamine biosynthesisAnalysis of linkageGenetic contributionModel systemRisk allelesDevelopmental neuropsychiatric disordersDecarboxylaseBiosynthesisGenesTourette syndromeMutationsAllelesEnzymeInheritanceNeuropsychiatric disordersPedigree
1999
Obstetrical Complications and Childhood-Onset Schizophrenia
Nicolson R, Malaspina D, Giedd JN, Hamburger S, Lenane M, Bedwell J, Fernandez T, Berman A, Susser E, Rapoport JL. Obstetrical Complications and Childhood-Onset Schizophrenia. American Journal Of Psychiatry 1999, 156: 1650-1652. PMID: 10518182, DOI: 10.1176/ajp.156.10.1650.Peer-Reviewed Original ResearchMeSH KeywordsAge of OnsetComorbidityFamilyFemaleGenetic Predisposition to DiseaseHumansIncidenceMaleMedical RecordsObstetric Labor ComplicationsPregnancyPregnancy ComplicationsSchizophreniaSex Factors