2019
Are serum brain-derived neurotrophic factor concentrations related to brain structure and psychopathology in late childhood and early adolescence?
de Araujo C, Swardfager W, Zugman A, Cogo-Moreira H, Belangero S, Ota V, Spindola L, Hakonarson H, Pellegrino R, Gadelha A, Salum G, Pan P, Mansur R, Hoexter M, Picon F, Sato J, Brietzke E, Grassi-Oliveira R, Rohde L, Miguel E, Bressan R, Jackowski A. Are serum brain-derived neurotrophic factor concentrations related to brain structure and psychopathology in late childhood and early adolescence? CNS Spectrums 2019, 25: 790-796. PMID: 31845634, DOI: 10.1017/s1092852919001688.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentBiomarkersBrainBrain-Derived Neurotrophic FactorChildFemaleGenotypeHumansMagnetic Resonance ImagingMaleMental DisordersPolymorphism, Single NucleotideConceptsSerum BDNF concentrationsBrain-derived neurotrophic factorBDNF concentrationsBDNF genotypeCortical thicknessPsychiatric disordersSerum brain-derived neurotrophic factor (BDNF) concentrationsBrain-derived neurotrophic factor concentrationSubcortical volumesMental disordersWell-Being Behavior AssessmentBrain structuresBDNF serum concentrationsNeurotrophic factor concentrationsPeripheral blood concentrationsHigh Risk Cohort StudyLate childhoodAdult psychiatric disordersLarge independent samplesCohort studyNeurotrophic factorCortical maturationSerum concentrationsBlood concentrationsMet carriersGenetic risk for Alzheimer's disease and functional brain connectivity in children and adolescents
Axelrud L, Sato J, Santoro M, Talarico F, Pine D, Rohde L, Zugman A, Junior E, Bressan R, Grassi-Oliveira R, Pan P, Hoffmann M, Simioni A, Guinjoan S, Hakonarson H, Brietzke E, Gadelha A, Pellegrino da Silva R, Hoexter M, Miguel E, Belangero S, Salum G. Genetic risk for Alzheimer's disease and functional brain connectivity in children and adolescents. Neurobiology Of Aging 2019, 82: 10-17. PMID: 31376729, PMCID: PMC7658444, DOI: 10.1016/j.neurobiolaging.2019.06.011.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAlzheimer DiseaseBrainBrazilChildCross-Sectional StudiesFemaleFunctional NeuroimagingGenetic Predisposition to DiseaseHumansMaleNerve NetPolymorphism, Single NucleotideConceptsAlzheimer's diseaseAD-PRSBrain connectivityGenetic riskRight superior temporal gyrusFunctional brain connectivityMagnetic resonance imagingInhibitory controlSuperior temporal gyrusTau pathologyAD developmentPolygenic risk scoresRisk scoreRight precuneusResonance imagingTau proteinTemporal gyrusDiseaseBrain connectionsEarly lifePathology networkFunctional networksRiskPorto AlegreMemory performanceEffects of the interaction between genetic factors and maltreatment on child and adolescent psychiatric disorders
Carvalho C, Pan P, Ota V, Spindola L, Xavier G, Santoro M, Mazzotti D, Pellegrino R, Hakonarson H, Rohde L, Miguel E, Gadelha A, Bressan R, Belangero S. Effects of the interaction between genetic factors and maltreatment on child and adolescent psychiatric disorders. Psychiatry Research 2019, 273: 575-577. PMID: 30716596, DOI: 10.1016/j.psychres.2019.01.078.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdolescent BehaviorBrazilChildChild AbuseFemaleGene-Environment InteractionHumansMaleNeurodevelopmental DisordersPolymorphism, Single NucleotideProspective StudiesConceptsMental disordersSingle nucleotide polymorphismsSchool-based prospective studyAdolescent psychiatric disordersBonferroni multiple comparison correctionChild maltreatmentProspective studyPsychiatric disordersMultiple comparison correctionSignificant associationGenetic factorsDisordersNucleotide polymorphismsPsychopathologyLogistic modelMaltreatment
2017
Effects of the brain-derived neurotropic factor variant Val66Met on cortical structure in late childhood and early adolescence
de Araujo C, Zugman A, Swardfager W, Belangero S, Ota V, Spindola L, Hakonarson H, Pellegrino R, Gadelha A, Salum G, Pan P, de Moura L, Del Aquilla M, Picon F, Amaro E, Sato J, Brietzke E, Grassi-Oliveira R, Rohde L, Miguel E, Bressan R, Jackowski A. Effects of the brain-derived neurotropic factor variant Val66Met on cortical structure in late childhood and early adolescence. Journal Of Psychiatric Research 2017, 98: 51-58. PMID: 29288952, DOI: 10.1016/j.jpsychires.2017.12.008.Peer-Reviewed Original ResearchMeSH KeywordsBrain-Derived Neurotrophic FactorBrazilCerebral CortexChildChild DevelopmentCohort StudiesFemaleHumansMagnetic Resonance ImagingMaleMental DisordersPolymorphism, Single NucleotideConceptsPsychiatric disordersVal66Met polymorphismCortical thicknessBrain-derived neurotrophic factor (BDNF) Val66Met polymorphismRegional structural brain changesNeurotrophic factor Val66Met polymorphismPrefrontal cortexStructural brain changesLateral temporal cortexEffect of Val66MetBilateral prefrontal cortexVal66Met effectsWindow of vulnerabilityCortical maturationBrain changesOccipital lobeMet carriersAtypical neurodevelopmentMRI scansPsychiatric diagnosisTemporal cortexDiagnosis interactionVal66MetNeuropsychiatric disordersBrain morphology
2016
Whole-exome sequencing in obsessive-compulsive disorder identifies rare mutations in immunological and neurodevelopmental pathways
Cappi C, Brentani H, Lima L, Sanders SJ, Zai G, Diniz BJ, Reis VN, Hounie AG, Conceição do Rosário M, Mariani D, Requena GL, Puga R, Souza-Duran FL, Shavitt RG, Pauls DL, Miguel EC, Fernandez TV. Whole-exome sequencing in obsessive-compulsive disorder identifies rare mutations in immunological and neurodevelopmental pathways. Translational Psychiatry 2016, 6: e764-e764. PMID: 27023170, PMCID: PMC4872454, DOI: 10.1038/tp.2016.30.Peer-Reviewed Original ResearchConceptsSingle nucleotide variantsPPI networkPathway analysisProtein-protein interaction networkGenome-wide association studiesNovo single nucleotide variantsParticular biological pathwaysRare genetic variationDisease gene prioritizationDirect molecular interactionWhole-exome sequencing studiesGene discoveryNetwork genesSpecific risk genesNetwork enrichmentGenetic variationInteraction networksGene prioritizationCandidate genesAssociation studiesBiological pathwaysSequencing platformsSequencing studiesWhole-exome sequencingGenesAn integrative approach to investigate the respective roles of single-nucleotide variants and copy-number variants in Attention-Deficit/Hyperactivity Disorder
de Araújo Lima L, Feio-dos-Santos A, Belangero S, Gadelha A, Bressan R, Salum G, Pan P, Moriyama T, Graeff-Martins A, Tamanaha A, Alvarenga P, Krieger F, Fleitlich-Bilyk B, Jackowski A, Brietzke E, Sato J, Polanczyk G, Mari J, Manfro G, do Rosário M, Miguel E, Puga R, Tahira A, Souza V, Chile T, Gouveia G, Simões S, Chang X, Pellegrino R, Tian L, Glessner J, Hashimoto R, Rohde L, Sleiman P, Hakonarson H, Brentani H. An integrative approach to investigate the respective roles of single-nucleotide variants and copy-number variants in Attention-Deficit/Hyperactivity Disorder. Scientific Reports 2016, 6: 22851. PMID: 26947246, PMCID: PMC4780010, DOI: 10.1038/srep22851.Peer-Reviewed Original ResearchConceptsCopy number variantsProtein-protein interaction networkDe novo CNVsSingle nucleotide variantsGenetic architectureNew genesInteraction networksOnly geneFunctional analysisCNV studiesNovo CNVsGenesCell adhesionGenetic variantsExome dataIntegrative approachPathwayGenetic susceptibilityVariantsGWASTriosRespective rolesSilicoCNVsSNVs
2015
COMT and MAO-A Polymorphisms and Obsessive-Compulsive Disorder: A Family-Based Association Study
Sampaio A, Hounie A, Petribú K, Cappi C, Morais I, Vallada H, do Rosário M, Stewart S, Fargeness J, Mathews C, Arnold P, Hanna G, Richter M, Kennedy J, Fontenelle L, de Bragança Pereira C, Pauls D, Miguel E. COMT and MAO-A Polymorphisms and Obsessive-Compulsive Disorder: A Family-Based Association Study. PLOS ONE 2015, 10: e0119592. PMID: 25793616, PMCID: PMC4368617, DOI: 10.1371/journal.pone.0119592.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAllelesCatechol O-MethyltransferaseChildEpistasis, GeneticFamilyFemaleGene FrequencyGenetic Association StudiesGenetic Predisposition to DiseaseGenotypeHaplotypesHumansLinkage DisequilibriumMaleMonoamine OxidaseObsessive-Compulsive DisorderPhenotypePolymorphism, Single NucleotideYoung AdultConceptsAssociation studiesBroad spectrum phenotypesTransmission disequilibrium analysisSingle geneSingle nucleotide polymorphismsGenetic association studiesGene-gene interactionsGenesClassical case-control designDisequilibrium analysisGenetic componentAssociation investigationsEpistatic influencesPhenotypePolymorphismSpectrum phenotypeEpistasisOCD susceptibilityAlternative strategyRoleNarrow phenotype
2014
Cross-Disorder Genome-Wide Analyses Suggest a Complex Genetic Relationship Between Tourette’s Syndrome and OCD
Yu D, Mathews CA, Scharf JM, Neale BM, Davis LK, Gamazon ER, Derks EM, Evans P, Edlund CK, Crane J, Fagerness JA, Osiecki L, Gallagher P, Gerber G, Haddad S, Illmann C, McGrath LM, Mayerfeld C, Arepalli S, Barlassina C, Barr CL, Bellodi L, Benarroch F, Berrió GB, Bienvenu OJ, Black DW, Bloch MH, Brentani H, Bruun RD, Budman CL, Camarena B, Campbell DD, Cappi C, Silgado JC, Cavallini MC, Chavira DA, Chouinard S, Cook EH, Cookson MR, Coric V, Cullen B, Cusi D, Delorme R, Denys D, Dion Y, Eapen V, Egberts K, Falkai P, Fernandez T, Fournier E, Garrido H, Geller D, Gilbert DL, Girard SL, Grabe HJ, Grados MA, Greenberg BD, Gross-Tsur V, Grünblatt E, Hardy J, Heiman GA, Hemmings SM, Herrera LD, Hezel DM, Hoekstra PJ, Jankovic J, Kennedy JL, King RA, Konkashbaev AI, Kremeyer B, Kurlan R, Lanzagorta N, Leboyer M, Leckman JF, Lennertz L, Liu C, Lochner C, Lowe TL, Lupoli S, Macciardi F, Maier W, Manunta P, Marconi M, McCracken JT, Mesa Restrepo SC, Moessner R, Moorjani P, Morgan J, Muller H, Murphy DL, Naarden AL, Nurmi E, Ochoa WC, Ophoff RA, Pakstis AJ, Pato MT, Pato CN, Piacentini J, Pittenger C, Pollak Y, Rauch SL, Renner T, Reus VI, Richter MA, Riddle MA, Robertson MM, Romero R, Rosário MC, Rosenberg D, Ruhrmann S, Sabatti C, Salvi E, Sampaio AS, Samuels J, Sandor P, Service SK, Sheppard B, Singer HS, Smit JH, Stein DJ, Strengman E, Tischfield JA, Turiel M, Valencia Duarte AV, Vallada H, Veenstra-VanderWeele J, Walitza S, Wang Y, Weale M, Weiss R, Wendland JR, Westenberg HG, Shugart YY, Hounie AG, Miguel EC, Nicolini H, Wagner M, Ruiz-Linares A, Cath DC, McMahon W, Posthuma D, Oostra BA, Nestadt G, Rouleau GA, Purcell S, Jenike MA, Heutink P, Hanna GL, Conti DV, Arnold PD, Freimer NB, Stewart SE, Knowles JA, Cox NJ, Pauls DL. Cross-Disorder Genome-Wide Analyses Suggest a Complex Genetic Relationship Between Tourette’s Syndrome and OCD. American Journal Of Psychiatry 2014, 172: 82-93. PMID: 25158072, PMCID: PMC4282594, DOI: 10.1176/appi.ajp.2014.13101306.Peer-Reviewed Original ResearchMeSH KeywordsAdultComorbidityFemaleGenome-Wide Association StudyHumansMaleObsessive-Compulsive DisorderPolymorphism, Single NucleotidePsychiatric Status Rating ScalesSeverity of Illness IndexTourette SyndromeConceptsGenome-wide association studiesSingle nucleotide polymorphismsPolygenic score analysisGene expression levelsGenetic architecturePhenotypic varianceCombined genome-wide association studyFunctional variantsPolygenic componentPolygenic signalSignificant polygenic componentExpression levelsGWAS summary statisticsAncestry-matched controlsBrain gene expression levelsComplex genetic relationshipsHeritable neurodevelopmental disorderTrue functional variantsParent-child triosGWAS signalsIndividual single nucleotide polymorphismsWide analysisGenetic variationUnderlying genetic susceptibilityAssociation studiesCopy 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 Research
2013
Partitioning the Heritability of Tourette Syndrome and Obsessive Compulsive Disorder Reveals Differences in Genetic Architecture
Davis LK, Yu D, Keenan CL, Gamazon ER, Konkashbaev AI, Derks EM, Neale BM, Yang J, Lee SH, Evans P, Barr CL, Bellodi L, Benarroch F, Berrio GB, Bienvenu OJ, Bloch MH, Blom RM, Bruun RD, Budman CL, Camarena B, Campbell D, Cappi C, Silgado J, Cath DC, Cavallini MC, Chavira DA, Chouinard S, Conti DV, Cook EH, Coric V, Cullen BA, Deforce D, Delorme R, Dion Y, Edlund CK, Egberts K, Falkai P, Fernandez TV, Gallagher PJ, Garrido H, Geller D, Girard SL, Grabe HJ, Grados MA, Greenberg BD, Gross-Tsur V, Haddad S, Heiman GA, Hemmings SM, Hounie AG, Illmann C, Jankovic J, Jenike MA, Kennedy JL, King RA, Kremeyer B, Kurlan R, Lanzagorta N, Leboyer M, Leckman JF, Lennertz L, Liu C, Lochner C, Lowe TL, Macciardi F, McCracken JT, McGrath LM, Restrepo S, Moessner R, Morgan J, Muller H, Murphy DL, Naarden AL, Ochoa WC, Ophoff RA, Osiecki L, Pakstis AJ, Pato MT, Pato CN, Piacentini J, Pittenger C, Pollak Y, Rauch SL, Renner TJ, Reus VI, Richter MA, Riddle MA, Robertson MM, Romero R, Rosàrio MC, Rosenberg D, Rouleau GA, Ruhrmann S, Ruiz-Linares A, Sampaio AS, Samuels J, Sandor P, Sheppard B, Singer HS, Smit JH, Stein DJ, Strengman E, Tischfield JA, Duarte A, Vallada H, Van Nieuwerburgh F, Veenstra-VanderWeele J, Walitza S, Wang Y, Wendland JR, Westenberg HG, Shugart YY, Miguel EC, McMahon W, Wagner M, Nicolini H, Posthuma D, Hanna GL, Heutink P, Denys D, Arnold PD, Oostra BA, Nestadt G, Freimer NB, Pauls DL, Wray NR, Stewart SE, Mathews CA, Knowles JA, Cox NJ, Scharf JM. Partitioning the Heritability of Tourette Syndrome and Obsessive Compulsive Disorder Reveals Differences in Genetic Architecture. PLOS Genetics 2013, 9: e1003864. PMID: 24204291, PMCID: PMC3812053, DOI: 10.1371/journal.pgen.1003864.Peer-Reviewed Original ResearchMeSH KeywordsGene FrequencyGenome-Wide Association StudyHumansObsessive-Compulsive DisorderPhenotypePolymorphism, Single NucleotideQuantitative Trait, HeritableTourette SyndromeConceptsGenome-wide complex trait analysisExpression quantitative trait lociGenetic architectureGenetic correlationsGenome-wide common variant dataQuantitative trait lociComplex trait analysisDistinct genetic architecturesGenomic architectureGenomic elementsFunctional annotationMinor allele frequencyTrait lociPrevious heritability estimatesMAF binsGWAS studiesGene expressionTrait analysisHeritabilityGenetic overlapVariant dataHeritability estimatesAllele frequenciesCommon variationSNPs
2012
Genome-wide association study of obsessive-compulsive disorder
Stewart SE, Yu D, Scharf JM, Neale BM, Fagerness JA, Mathews CA, Arnold PD, Evans PD, Gamazon ER, Osiecki L, McGrath L, Haddad S, Crane J, Hezel D, Illman C, Mayerfeld C, Konkashbaev A, Liu C, Pluzhnikov A, Tikhomirov A, Edlund C, Rauch S, Moessner R, Falkai P, Maier W, Ruhrmann S, Grabe H, Lennertz L, Wagner M, Bellodi L, Cavallini M, Richter M, Cook E, Kennedy J, Rosenberg D, Stein D, Hemmings S, Lochner C, Azzam A, Chavira D, Fournier E, Garrido H, Sheppard B, Umaña P, Murphy D, Wendland J, Veenstra-VanderWeele J, Denys D, Blom R, Deforce D, Van Nieuwerburgh F, Westenberg H, Walitza S, Egberts K, Renner T, Miguel E, Cappi C, Hounie A, Conceição do Rosário M, Sampaio A, Vallada H, Nicolini H, Lanzagorta N, Camarena B, Delorme R, Leboyer M, Pato C, Pato M, Voyiaziakis E, Heutink P, Cath D, Posthuma D, Smit J, Samuels J, Bienvenu O, Cullen B, Fyer A, Grados M, Greenberg B, McCracken J, Riddle M, Wang Y, Coric V, Leckman J, Bloch M, Pittenger C, Eapen V, Black D, Ophoff R, Strengman E, Cusi D, Turiel M, Frau F, Macciardi F, Gibbs J, Cookson M, Singleton A, Hardy J, Crenshaw A, Parkin M, Mirel D, Conti D, Purcell S, Nestadt G, Hanna G, Jenike M, Knowles J, Cox N, Pauls D. Genome-wide association study of obsessive-compulsive disorder. Molecular Psychiatry 2012, 18: 788-798. PMID: 22889921, PMCID: PMC4218751, DOI: 10.1038/mp.2012.85.Peer-Reviewed Original ResearchConceptsExpression quantitative trait lociSingle nucleotide polymorphismsGenome-wide significant levelGenome-wide significance thresholdX-chromosome single nucleotide polymorphismsGenome-wide association studiesTrio-based analysisQuantitative trait lociAncestry-matched controlsComplex genetic etiologyTrait lociCase-control association analysisMethylation QTLsGenetic variationGene expressionAssociation studiesTop signalsAssociation analysisBroader roleSignificant enrichmentSNP microarraysCase-control sampleNucleotide polymorphismsGenetic etiologySignificance threshold
2006
Association of polymorphisms within the promoter region of the tumor necrosis factor-α with clinical outcomes of rheumatic fever
Ramasawmy R, Faé K, Spina G, Victora G, Tanaka A, Palácios S, Hounie A, Miguel E, Oshiro S, Goldberg A, Kalil J, Guilherme L. Association of polymorphisms within the promoter region of the tumor necrosis factor-α with clinical outcomes of rheumatic fever. Molecular Immunology 2006, 44: 1873-1878. PMID: 17079017, DOI: 10.1016/j.molimm.2006.10.001.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAortic DiseasesAutoimmune DiseasesChildChoreaCohort StudiesFemaleGenetic Predisposition to DiseaseHumansMaleMyocarditisPolymorphism, Single NucleotidePredictive Value of TestsQuantitative Trait LociRheumatic Heart DiseaseStreptococcal InfectionsStreptococcus pyogenesTumor Necrosis Factor-alphaConceptsRheumatic feverRF patientsClinical outcomesHealthy controlsTNFA geneMinor alleleRF/RHDAortic valve lesionsRecognition of autoantigensStratification of patientsTumor necrosis factorAssociation of polymorphismsMild carditisValve lesionsAdaptive armsSydenham's choreaAutoimmune diseasesHeart diseaseInflammatory diseasesNecrosis factorBorderline associationG-308APatientsImmune systemClinical phenotype