Somatic mosaicism in schizophrenia brains reveals prenatal mutational processes
Maury E, Jones A, Seplyarskiy V, Nguyen T, Rosenbluh C, Bae T, Wang Y, Abyzov A, Khoshkhoo S, Chahine Y, Zhao S, Venkatesh S, Root E, Voloudakis G, Roussos P, Network B, Park P, Akbarian S, Brennand K, Reilly S, Lee E, Sunyaev S, Walsh C, Chess A. Somatic mosaicism in schizophrenia brains reveals prenatal mutational processes. Science 2024, 386: 217-224. PMID: 39388546, PMCID: PMC11490355, DOI: 10.1126/science.adq1456.Peer-Reviewed Original ResearchConceptsTranscription factor binding sitesWhole-genome sequencingOpen chromatinMutational processesSomatic mutationsFactor binding sitesSchizophrenia casesSchizophrenia risk genesSomatic mosaicismSomatic variantsRisk genesG mutationGene expressionGermline mutationsBinding sitesGenesMutationsIncreased somatic mutationsChromatinMosaic somatic mutationsPrenatal neurogenesisContext of schizophreniaBrain neuronsSchizophrenia brainVariants42. STRESS EXPOSURE DYNAMICALLY REGULATES EQTL ACTIVITY IN THE POST-MORTEM BRAIN AND IN HIPSC-DERIVED NEURONS
Seah C, Signer R, Young H, Hicks E, Rusielewicz T, Bader H, Xu C, Breen M, Paull D, Yehuda R, Girgenti M, Brennand K, Huckins L. 42. STRESS EXPOSURE DYNAMICALLY REGULATES EQTL ACTIVITY IN THE POST-MORTEM BRAIN AND IN HIPSC-DERIVED NEURONS. European Neuropsychopharmacology 2024, 87: 71-72. DOI: 10.1016/j.euroneuro.2024.08.156.Peer-Reviewed Original ResearchPost-mortem brainsTranscription factor binding sitesAbsence of cellular stressCombat-exposed veteransFactor binding sitesImpact gene expressionBinding sitesGR binding sitesPositive regulatory activityMotif enrichmentSequence readsCRISPRi screenOpen chromatinFunctional annotationBrain regionsTraumatic stressCRISPR screensEQTLTraumatic experiencesLeading locusPTSDPerturbed genesRegulatory architectureTranscriptomic activityTranscriptomic response