2023
Integrating genetics and transcriptomics to study major depressive disorder: a conceptual framework, bioinformatic approaches, and recent findings
Hicks E, Seah C, Cote A, Marchese S, Brennand K, Nestler E, Girgenti M, Huckins L. Integrating genetics and transcriptomics to study major depressive disorder: a conceptual framework, bioinformatic approaches, and recent findings. Translational Psychiatry 2023, 13: 129. PMID: 37076454, PMCID: PMC10115809, DOI: 10.1038/s41398-023-02412-7.Peer-Reviewed Original ResearchConceptsBioinformatics approachTranscriptomic dataBrain transcriptomeGenome-wide analysisDynamic transcriptional landscapeBrain gene expression dataGene expression dataTranscriptional landscapeTranscriptomic studiesIntegrating GeneticExpression dataPhenotypic signaturesGenomic driversTranscriptomeMajor depressive disorderValuable resourceRecent findingsEnvironmental influencesTranscriptomicsDepressive disorderGeneticsMultiple approachesPathophysiology of depressionSignaturesDysregulation
2022
Reduced LYNX1 expression in transcriptome of human iPSC-derived neural progenitors modeling fragile X syndrome
Talvio K, Minkeviciene R, Townsley K, Achuta V, Huckins L, Corcoran P, Brennand K, Castrén M. Reduced LYNX1 expression in transcriptome of human iPSC-derived neural progenitors modeling fragile X syndrome. Frontiers In Cell And Developmental Biology 2022, 10: 1034679. PMID: 36506088, PMCID: PMC9731341, DOI: 10.3389/fcell.2022.1034679.Peer-Reviewed Original ResearchInduced pluripotent stem cellsFragile X syndromeHuman induced pluripotent stem cellsNeural progenitorsX syndromeEarly gene expression changesGene expression changesPatient-derived induced pluripotent stem cellsTriplet repeat instabilityFunctional enrichment analysisHuman neural progenitorsPluripotent stem cellsRNA splicingPhenotypic variationIntellectual disability syndromeEnrichment analysisExpression changesRepeat instabilityMolecular mechanismsProtein resultsGrowth factor pathwaysInsulin-like growth factor (IGF) pathwayAltered expressionStem cellsTranscriptomePopulation-level variation in enhancer expression identifies disease mechanisms in the human brain
Dong P, Hoffman G, Apontes P, Bendl J, Rahman S, Fernando M, Zeng B, Vicari J, Zhang W, Girdhar K, Townsley K, Misir R, Brennand K, Haroutunian V, Voloudakis G, Fullard J, Roussos P. Population-level variation in enhancer expression identifies disease mechanisms in the human brain. Nature Genetics 2022, 54: 1493-1503. PMID: 36163279, PMCID: PMC9547946, DOI: 10.1038/s41588-022-01170-4.Peer-Reviewed Original ResearchConceptsExpression quantitative trait lociPopulation-level variationTranscriptome-wide association studyQuantitative trait lociSpecific transcriptomeTrait lociTrait heritabilitySpecific transcriptionEnhancer functionGenetic mechanismsTarget genesAssociation studiesDisease locusNeuropsychiatric diseasesRisk variantsGenesRobust expressionTranscriptomeFunctional interpretationDisease mechanismsEnhancerDiseased statesLociHuman brainBrain samples
2017
Common developmental genome deprogramming in schizophrenia — Role of Integrative Nuclear FGFR1 Signaling (INFS)
Narla S, Lee Y, Benson C, Sarder P, Brennand K, Stachowiak E, Stachowiak M. Common developmental genome deprogramming in schizophrenia — Role of Integrative Nuclear FGFR1 Signaling (INFS). Schizophrenia Research 2017, 185: 17-32. PMID: 28094170, PMCID: PMC5507209, DOI: 10.1016/j.schres.2016.12.012.Peer-Reviewed Original ResearchMeSH KeywordsAdultCell DifferentiationCells, CulturedFemaleGene Expression Regulation, DevelopmentalGene Regulatory NetworksGenomeGenomicsHumansInduced Pluripotent Stem CellsMaleMicroRNAsModels, BiologicalMutationReceptor, Fibroblast Growth Factor, Type 1Receptor, Notch1SchizophreniaSignal TransductionTranscriptomeYoung AdultConceptsMRNA networkMajor developmental pathwaysIntegrative nuclear FGFR1MiRNA-mRNA networkHuman gene promotersCommon developmental genomesMiRNA genesMiRNA transcriptomeGene networksUpregulated genesGene promoterNuclear FGFR1Genomic etiologyGene dysregulationDisease ontogenyNuclear formGlobal dysregulationDevelopmental pathwaysGenesNeuron formationDistinct pathwaysConcerted actionPotential therapeutic targetTranscriptomeGenome