2023
STRESS IN A DISH: MODELING THE IMPACT OF COMMON GENETIC VARIATION ON STRESS RESPONSE IN HIPSC-DERIVED NEURONS IN PTSD
Seah C, Signer R, Young H, Kozik E, Rusielewicz T, Bader H, Xu C, de Pins A, Breen M, Paull D, Yehuda R, Girgenti M, Brennand K, Huckins L. STRESS IN A DISH: MODELING THE IMPACT OF COMMON GENETIC VARIATION ON STRESS RESPONSE IN HIPSC-DERIVED NEURONS IN PTSD. European Neuropsychopharmacology 2023, 75: s40. DOI: 10.1016/j.euroneuro.2023.08.081.Peer-Reviewed Original ResearchCommon genetic variationGenetic variationStress responseCell typesEQTL associationsTranscriptional stress responseGenomic risk lociTissue-specific mannerChIP-seq datasetsCell type deconvolutionCommon genetic variantsPost-mortem brainsGene expression signaturesHiPSC-derived neuronsTranscription factorsSuch lociCatalog genesRisk lociGenetic studiesExpression signaturesGenetic variantsRegulatory activityGenesEQTLsMechanistic understanding
2020
Massively parallel techniques for cataloguing the regulome of the human brain
Townsley KG, Brennand KJ, Huckins LM. Massively parallel techniques for cataloguing the regulome of the human brain. Nature Neuroscience 2020, 23: 1509-1521. PMID: 33199899, PMCID: PMC8018778, DOI: 10.1038/s41593-020-00740-1.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsRegulatory elementsTarget genesParallel reporter assaysPutative regulatory elementsNon-coding regionsDisease-associated lociSpecific expression patternsCandidate risk lociPluripotent stem cellsHigh-throughput assaysRelevant molecular pathwaysTranscriptional responseRegulatory architectureRisk lociExpression patternsReporter assaysComplex brain disordersMolecular pathwaysRegulomeStem cellsRisk architectureGenetic riskGenesLociGenetic diagnosisTranscriptional signatures of participant-derived neural progenitor cells and neurons implicate altered Wnt signaling in Phelan-McDermid syndrome and autism
Breen MS, Browne A, Hoffman GE, Stathopoulos S, Brennand K, Buxbaum JD, Drapeau E. Transcriptional signatures of participant-derived neural progenitor cells and neurons implicate altered Wnt signaling in Phelan-McDermid syndrome and autism. Molecular Autism 2020, 11: 53. PMID: 32560742, PMCID: PMC7304190, DOI: 10.1186/s13229-020-00355-0.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAutistic DisorderChildChild, PreschoolChromosome DeletionChromosome DisordersChromosomes, Human, Pair 22FemaleGene Expression ProfilingGene Expression RegulationHumansInduced Pluripotent Stem CellsMaleNeural Stem CellsNeuronsReproducibility of ResultsWnt Signaling PathwayConceptsNeural progenitor cellsTranscriptional signatureGene co-expression network analysisHiPSC-NPCsCo-expression network analysisIndependent biological samplesHiPSC-derived neural cellsProgenitor cellsPostsynaptic density genesDistinct transcriptional signaturesGenetic risk lociHuman-induced pluripotent stem cellsPluripotent stem cellsPotassium channel activityProtein translationSpecific neurobiological pathwaysTranscriptional differencesEmbryonic developmentLoss of SHANK3Risk lociHiPSC neuronsMorphological phenotypesWnt pathwayGenesHiPSC clones
2017
MEF2C transcription factor is associated with the genetic and epigenetic risk architecture of schizophrenia and improves cognition in mice
Mitchell A, Javidfar B, Pothula V, Ibi D, Shen E, Peter C, Bicks L, Fehr T, Jiang Y, Brennand K, Neve R, Gonzalez-Maeso J, Akbarian S. MEF2C transcription factor is associated with the genetic and epigenetic risk architecture of schizophrenia and improves cognition in mice. Molecular Psychiatry 2017, 23: 123-132. PMID: 28115742, PMCID: PMC5966823, DOI: 10.1038/mp.2016.254.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrainChromatin ImmunoprecipitationCognition DisordersComputational BiologyDisease Models, AnimalEpigenomicsGene Expression RegulationGreen Fluorescent ProteinsHistonesMEF2 Transcription FactorsMiceMice, Inbred C57BLMice, KnockoutNerve Tissue ProteinsNeuronsPolymorphism, Single NucleotideSchizophreniaTransduction, GeneticConceptsTherapeutic potentialPrefrontal projection neuronsNeuron-specific promoterUnexplored therapeutic potentialProjection neuronsDrug challengeDisease casesRelated disordersRisk architecturePrefrontal cortexSchizophreniaSingle nucleotide polymorphismsCognitive performancePsychiatric Genomics ConsortiumNeuronal genomeH3K4 hypermethylationRisk lociCognitive enhancement
2014
A Role for Noncoding Variation in Schizophrenia
Roussos P, Mitchell A, Voloudakis G, Fullard J, Pothula V, Tsang J, Stahl E, Georgakopoulos A, Ruderfer D, Charney A, Okada Y, Siminovitch K, Worthington J, Padyukov L, Klareskog L, Gregersen P, Plenge R, Raychaudhuri S, Fromer M, Purcell S, Brennand K, Robakis N, Schadt E, Akbarian S, Sklar P. A Role for Noncoding Variation in Schizophrenia. Cell Reports 2014, 9: 1417-1429. PMID: 25453756, PMCID: PMC4255904, DOI: 10.1016/j.celrep.2014.10.015.Peer-Reviewed Original ResearchMeSH KeywordsArthritis, RheumatoidCalcium Channels, L-TypeDatabases, GeneticDNA, IntergenicEnhancer Elements, GeneticGene Expression RegulationGenetic LociGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMolecular Sequence AnnotationOrgan SpecificityPolymorphism, Single NucleotidePromoter Regions, GeneticProtein BindingRisk FactorsSchizophreniaConceptsExpression quantitative trait lociGenome-wide significant lociCommon variant lociQuantitative trait lociPluripotent stem cell-derived neuronsDistal regulatory elementsStem cell-derived neuronsPotential physical interactionsCell-derived neuronsRegulatory element sequencesPotential functional roleGenome architectureChromosomal loopingTranscriptional regulationFunctional annotationTrait lociSignificant lociNoncoding SNPsRegulatory elementsNoncoding variationsRisk lociVariant lociUnknown functionFunctional linkElement sequences