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 ResearchConceptsDNA 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
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 ResearchConceptsWhole-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
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
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
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
2014
The inheritance of Tourette Disorder: A review
Pauls DL, Fernandez TV, Mathews CA, State MW, Scharf JM. The inheritance of Tourette Disorder: A review. Journal Of Obsessive-Compulsive And Related Disorders 2014, 3: 380-385. PMID: 25506544, PMCID: PMC4260404, DOI: 10.1016/j.jocrd.2014.06.003.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsGenetic variationGenome-wide associationGenetic mechanismsBiological pathwaysCausative genesCase-control sampleNumber variantsCommon variantsMultigenerational familiesGenetic factorsRecent studiesFamilyBroad spectrumGenesVariantsFamilial clusteringInheritanceNeuropsychiatric disordersNumerous studiesPathwayVariationGeorges Gilles deCytogenetic abnormalitiesNuclear familiesTranscriptome 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 interneuronsTranscriptsRNAThe 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