2025
Implications of gene Ă— environment interactions in post-traumatic stress disorder risk and treatment
Seah C, Sidamon-Eristoff A, Huckins L, Brennand K. Implications of gene Ă— environment interactions in post-traumatic stress disorder risk and treatment. Journal Of Clinical Investigation 2025, 135: e185102. PMID: 40026250, PMCID: PMC11870735, DOI: 10.1172/jci185102.Peer-Reviewed Original ResearchMeSH KeywordsFemaleGene-Environment InteractionGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMaleRisk FactorsStress Disorders, Post-TraumaticConceptsPost-traumatic stress disorderGene x environment interactionsGenetic component of riskLimitations of genetic studiesTreating post-traumatic stress disorderExposure to traumatic stressPost-traumatic stress disorder riskInteraction of traumaGenetic screeningGenetic studiesGenetic componentEnvironment interactionMolecular mechanismsStress disorderPTSD riskTraumatic exposureTraumatic stressTraumatic experiencesDisorder riskGenetic factorsNovel therapeuticsBiological mechanismsGWASGeneral populationGenes
2024
Genome-wide association analyses identify 95 risk loci and provide insights into the neurobiology of post-traumatic stress disorder
Nievergelt C, Maihofer A, Atkinson E, Chen C, Choi K, Coleman J, Daskalakis N, Duncan L, Polimanti R, Aaronson C, Amstadter A, Andersen S, Andreassen O, Arbisi P, Ashley-Koch A, Austin S, Avdibegoviç E, Babić D, Bacanu S, Baker D, Batzler A, Beckham J, Belangero S, Benjet C, Bergner C, Bierer L, Biernacka J, Bierut L, Bisson J, Boks M, Bolger E, Brandolino A, Breen G, Bressan R, Bryant R, Bustamante A, Bybjerg-Grauholm J, Bækvad-Hansen M, Børglum A, Børte S, Cahn L, Calabrese J, Caldas-de-Almeida J, Chatzinakos C, Cheema S, Clouston S, Colodro-Conde L, Coombes B, Cruz-Fuentes C, Dale A, Dalvie S, Davis L, Deckert J, Delahanty D, Dennis M, Desarnaud F, DiPietro C, Disner S, Docherty A, Domschke K, Dyb G, Kulenović A, Edenberg H, Evans A, Fabbri C, Fani N, Farrer L, Feder A, Feeny N, Flory J, Forbes D, Franz C, Galea S, Garrett M, Gelaye B, Gelernter J, Geuze E, Gillespie C, Goleva S, Gordon S, Goçi A, Grasser L, Guindalini C, Haas M, Hagenaars S, Hauser M, Heath A, Hemmings S, Hesselbrock V, Hickie I, Hogan K, Hougaard D, Huang H, Huckins L, Hveem K, Jakovljević M, Javanbakht A, Jenkins G, Johnson J, Jones I, Jovanovic T, Karstoft K, Kaufman M, Kennedy J, Kessler R, Khan A, Kimbrel N, King A, Koen N, Kotov R, Kranzler H, Krebs K, Kremen W, Kuan P, Lawford B, Lebois L, Lehto K, Levey D, Lewis C, Liberzon I, Linnstaedt S, Logue M, Lori A, Lu Y, Luft B, Lupton M, Luykx J, Makotkine I, Maples-Keller J, Marchese S, Marmar C, Martin N, MartĂnez-Levy G, McAloney K, McFarlane A, McLaughlin K, McLean S, Medland S, Mehta D, Meyers J, Michopoulos V, Mikita E, Milani L, Milberg W, Miller M, Morey R, Morris C, Mors O, Mortensen P, Mufford M, Nelson E, Nordentoft M, Norman S, Nugent N, O’Donnell M, Orcutt H, Pan P, Panizzon M, Pathak G, Peters E, Peterson A, Peverill M, Pietrzak R, Polusny M, Porjesz B, Powers A, Qin X, Ratanatharathorn A, Risbrough V, Roberts A, Rothbaum A, Rothbaum B, Roy-Byrne P, Ruggiero K, Rung A, Runz H, Rutten B, de Viteri S, Salum G, Sampson L, Sanchez S, Santoro M, Seah C, Seedat S, Seng J, Shabalin A, Sheerin C, Silove D, Smith A, Smoller J, Sponheim S, Stein D, Stensland S, Stevens J, Sumner J, Teicher M, Thompson W, Tiwari A, Trapido E, Uddin M, Ursano R, ValdimarsdĂłttir U, Van Hooff M, Vermetten E, Vinkers C, Voisey J, Wang Y, Wang Z, Waszczuk M, Weber H, Wendt F, Werge T, Williams M, Williamson D, Winsvold B, Winternitz S, Wolf C, Wolf E, Xia Y, Xiong Y, Yehuda R, Young K, Young R, Zai C, Zai G, Zervas M, Zhao H, Zoellner L, Zwart J, deRoon-Cassini T, van Rooij S, van den Heuvel L, Stein M, Ressler K, Koenen K. Genome-wide association analyses identify 95 risk loci and provide insights into the neurobiology of post-traumatic stress disorder. Nature Genetics 2024, 56: 792-808. PMID: 38637617, PMCID: PMC11396662, DOI: 10.1038/s41588-024-01707-9.Peer-Reviewed Original ResearchMeSH KeywordsGenetic LociGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansNeurobiologyPolymorphism, Single NucleotideStress Disorders, Post-TraumaticWhite PeopleConceptsMeta-analysis of genome-wide association studiesGenome-wide significant lociMulti-ancestry meta-analysisGenome-wide association analysisGenome-wide association studiesIndividuals of European ancestryPotential causal genesNative American ancestryMulti-omics approachPost-traumatic stress disorderAdmixed individualsSignificant lociRisk lociCausal genesAssociation studiesAssociation analysisFunctional genesTranscription factorsGenetic studiesAmerican ancestryEuropean ancestryAxon guidanceSynaptic structureLociGenes
2022
Modeling gene Ă— environment interactions in PTSD using human neurons reveals diagnosis-specific glucocorticoid-induced gene expression
Seah C, Breen M, Rusielewicz T, Bader H, Xu C, Hunter C, McCarthy B, Deans P, Chattopadhyay M, Goldberg J, Dobariya S, Desarnaud F, Makotkine I, Flory J, Bierer L, Staniskyte M, Noggle S, Huckins L, Paull D, Brennand K, Yehuda R. Modeling gene Ă— environment interactions in PTSD using human neurons reveals diagnosis-specific glucocorticoid-induced gene expression. Nature Neuroscience 2022, 25: 1434-1445. PMID: 36266471, PMCID: PMC9630117, DOI: 10.1038/s41593-022-01161-y.Peer-Reviewed Original ResearchMeSH KeywordsGene ExpressionGene-Environment InteractionGlucocorticoidsHumansInduced Pluripotent Stem CellsLeukocytes, MononuclearNeuronsStress Disorders, Post-TraumaticConceptsPost-traumatic stress disorderPeripheral blood mononuclear cellsGlucocorticoid-induced changesGlucocorticoid-induced gene expressionBlood mononuclear cellsIndividual clinical outcomesEnvironmental risk factorsHuman postmortem brainGlucocorticoid hypersensitivityClinical outcomesGlutamatergic neuronsMononuclear cellsRisk factorsHydrocortisone exposureSevere traumaPostmortem brainsHuman neuronsGlucocorticoid responseInduced neuronsStress disorderNeuronsNew therapeuticsGene expressionGene Ă— environment interactionsCombat veteransUsing phenotype risk scores to enhance gene discovery for generalized anxiety disorder and posttraumatic stress disorder
Wendt FR, Pathak GA, Deak JD, De Angelis F, Koller D, Cabrera-Mendoza B, Lebovitch DS, Levey DF, Stein MB, Kranzler HR, Koenen KC, Gelernter J, Huckins LM, Polimanti R. Using phenotype risk scores to enhance gene discovery for generalized anxiety disorder and posttraumatic stress disorder. Molecular Psychiatry 2022, 27: 2206-2215. PMID: 35181757, PMCID: PMC9133008, DOI: 10.1038/s41380-022-01469-y.Peer-Reviewed Original ResearchMeSH KeywordsAnxiety DisordersDepressive Disorder, MajorFemaleGenome-Wide Association StudyHumansMalePhenotypeRisk FactorsStress Disorders, Post-TraumaticAltered gene expression and PTSD symptom dimensions in World Trade Center responders
Marchese S, Cancelmo L, Diab O, Cahn L, Aaronson C, Daskalakis NP, Schaffer J, Horn SR, Johnson JS, Schechter C, Desarnaud F, Bierer LM, Makotkine I, Flory JD, Crane M, Moline JM, Udasin IG, Harrison DJ, Roussos P, Charney DS, Koenen KC, Southwick SM, Yehuda R, Pietrzak RH, Huckins LM, Feder A. Altered gene expression and PTSD symptom dimensions in World Trade Center responders. Molecular Psychiatry 2022, 27: 2225-2246. PMID: 35177824, DOI: 10.1038/s41380-022-01457-2.Peer-Reviewed Original ResearchMeSH KeywordsAnxietyChloride ChannelsGene ExpressionHumansRNA-Binding ProteinsSelf ReportSeptember 11 Terrorist AttacksStress Disorders, Post-TraumaticConceptsPTSD symptom dimensionsPosttraumatic stress disorderCAPS scoresAnxious arousal symptomsSymptom dimensionsWorld Trade Center rescueClinician-Administered PTSD Scale scoresBiomarker of PTSDArousal symptomsCD4 T cellsWorld Trade Center respondersDevelopment of PTSDTotal CAPS scoresCase/control statusTherapeutic target developmentIdentification of biomarkersClinical interview dataResponder cohortPTSD symptom severityPotential biological differencesWTC respondersT cellsGene expressionPTSD studiesPsychiatric disorders
2020
Analysis of Genetically Regulated Gene Expression Identifies a Prefrontal PTSD Gene, SNRNP35, Specific to Military Cohorts
Huckins L, Chatzinakos C, Breen M, Hartmann J, Klengel T, da Silva Almeida A, Dobbyn A, Girdhar K, Hoffman G, Klengel C, Logue M, Lori A, Maihofer A, Morrison F, Nguyen H, Park Y, Ruderfer D, Sloofman L, van Rooij S, Consortium P, Baker D, Chen C, Cox N, Duncan L, Geyer M, Glatt S, Im H, Risbrough V, Smoller J, Stein D, Yehuda R, Liberzon I, Koenen K, Jovanovic T, Kellis M, Miller M, Bacanu S, Nievergelt C, Buxbaum J, Sklar P, Ressler K, Stahl E, Daskalakis N. Analysis of Genetically Regulated Gene Expression Identifies a Prefrontal PTSD Gene, SNRNP35, Specific to Military Cohorts. Cell Reports 2020, 31: 107716. PMID: 32492425, PMCID: PMC7359754, DOI: 10.1016/j.celrep.2020.107716.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCase-Control StudiesCohort StudiesDexamethasoneDown-RegulationGene Expression RegulationGene Regulatory NetworksGenetic Predisposition to DiseaseHumansLeukocytesMaleMiceMice, Inbred C57BLMilitary PersonnelPrefrontal CortexRepressor ProteinsRibonucleoproteins, Small NuclearRNA InterferenceRNA, Small InterferingStress Disorders, Post-TraumaticConceptsPost-traumatic stress disorderGenetically regulated gene expressionPost-traumatic stress disorder casesDorsolateral prefrontal cortexGene expressionU12 intron splicingPrefrontal cortexStress disorderDeployment stressTranscriptome imputationTissue-specific gene expressionDifferential gene expressionMilitary cohortZNF140U12 intronsGenetic heterogeneityExpression changesFunctional roleExogenous glucocorticoidsPeripheral leukocytesEuropean cohortCortexCohortDisordersExpression
2018
Recent Genetics and Epigenetics Approaches to PTSD
Daskalakis N, Rijal C, King C, Huckins L, Ressler K. Recent Genetics and Epigenetics Approaches to PTSD. Current Psychiatry Reports 2018, 20: 30. PMID: 29623448, PMCID: PMC6486832, DOI: 10.1007/s11920-018-0898-7.Peer-Reviewed Original ResearchMeSH KeywordsEpigenesis, GeneticEpigenomicsGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansStress Disorders, Post-TraumaticConceptsPosttraumatic stress disorderTrauma exposureGenome-wide association studiesEpigenetic approachesTargeted genetic studiesEpigenome-wide studiesInduce epigenetic changesResponse to trauma exposureAssociation studiesAdult trauma exposureGenetic studiesNegative emotional symptomsEpigenetic alterationsEpigenetic changesFunctional regulationEpigenetic riskIntrusive memoriesStress disorderTraumatic exposureImpaired cognitionEmotional symptomsAvoidance behaviorDisability syndromeBiological riskElectronic medical records
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