2023
Activity-Dependent Transcriptional Program in NGN2+ Neurons Enriched for Genetic Risk for Brain-Related Disorders
Ma Y, Bendl J, Hartley B, Fullard J, Abdelaal R, Ho S, Kosoy R, Gochman P, Rapoport J, Hoffman G, Brennand K, Roussos P. Activity-Dependent Transcriptional Program in NGN2+ Neurons Enriched for Genetic Risk for Brain-Related Disorders. Biological Psychiatry 2023, 95: 187-198. PMID: 37454787, PMCID: PMC10787819, DOI: 10.1016/j.biopsych.2023.07.003.Peer-Reviewed Original ResearchConceptsTranscriptional programsBrain-related disordersGlutamatergic neuronsGene coexpression network analysisSignificant heritability enrichmentsEnhancer-promoter interactionsCoexpression network analysisDisease-associated genesExpression of genesLarge-scale geneticMultiomics data integrationChromatin accessibilityEpigenomic changesHeritability enrichmentGenetic regulationRegulatory elementsMultiple genesSequence variationGene expressionAxon guidanceGenetic riskPotassium chloride-induced depolarizationActivity-dependent changesDepolarization-induced changesGenes
2022
Using Stem Cell Models to Explore the Genetics Underlying Psychiatric Disorders: Linking Risk Variants, Genes, and Biology in Brain Disease
Brennand K. Using Stem Cell Models to Explore the Genetics Underlying Psychiatric Disorders: Linking Risk Variants, Genes, and Biology in Brain Disease. American Journal Of Psychiatry 2022, 179: 322-328. PMID: 35491564, DOI: 10.1176/appi.ajp.20220235.Commentaries, Editorials and LettersConceptsRisk variantsFunctional genomic studiesCell typesDiverse cell typesPatient-specific variantsStem cell modelGenomic studiesSignificant lociStem cell-based approachesGenetic studiesExciting questionsCell-based approachesEngineering strategiesGenetic profileNovel therapeutic interventionsCell modelPluripotent stem cell-based approachesVariantsComplex interplayGenetic riskCRISPRGenesLociBiologyTherapeutic interventions
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 diagnosisIntegration of CRISPR-engineering and hiPSC-based models of psychiatric genomics
Matos MR, Ho SM, Schrode N, Brennand KJ. Integration of CRISPR-engineering and hiPSC-based models of psychiatric genomics. Molecular And Cellular Neuroscience 2020, 107: 103532. PMID: 32712198, PMCID: PMC7484226, DOI: 10.1016/j.mcn.2020.103532.Peer-Reviewed Original ResearchConceptsPenetrant rare variantsDisease-associated variantsNeuronal cell typesPluripotent stem cellsGenomic engineeringFunctional characterizationComplex geneticsCRISPR engineeringCRISPR technologyIsogenic comparisonsPsychiatric genomicsCell typesGenetic variantsStem cellsIndividual variantsCommon variantsPolygenic disorderRare variantsVariantsComplex interplayGenomicsGenetic riskPleiotropyCRISPRGenetics
2019
CRISPR-based functional evaluation of schizophrenia risk variants
Rajarajan P, Flaherty E, Akbarian S, Brennand KJ. CRISPR-based functional evaluation of schizophrenia risk variants. Schizophrenia Research 2019, 217: 26-36. PMID: 31277978, PMCID: PMC6939156, DOI: 10.1016/j.schres.2019.06.017.Peer-Reviewed Original ResearchConceptsSchizophrenia-associated variantsPluripotent stem cellsCRISPR genome engineeringSchizophrenia risk variantsCellular functionsGenome engineeringGenomic studiesSchizophrenia lociList of variantsGene expressionPatient-specific humanGenotype dataRisk variantsStem cellsFunctional impactCommon variantsCRISPRPost-mortem brain tissueRecent findingsVariantsNeuropsychiatric diseasesPoint of convergenceGenetic riskLociSpecific effects