2023
Cross-Species Convergence of Brain Transcriptomic and Epigenomic Findings in Posttraumatic Stress Disorder: A Systematic Review
Núñez-Rios D, Martínez-Magaña J, Nagamatsu S, Krystal J, Martínez-González K, Giusti-Rodríguez P, Montalvo-Ortiz J. Cross-Species Convergence of Brain Transcriptomic and Epigenomic Findings in Posttraumatic Stress Disorder: A Systematic Review. Complex Psychiatry 2023, 9: 100-118. PMID: 37404872, PMCID: PMC10315001, DOI: 10.1159/000529536.Peer-Reviewed Original ResearchG protein-coupled receptorsPosttraumatic stress disorderEpigenomic findingsEpigenomic studiesEpigenomic profilesTranscriptomic modificationsEpigenetic studiesBrain transcriptomicsBiological pathwaysComplex multifactorial disorderGenesBrain tissueGene-environment interplayStress disorderSpeciesHuman postmortem samplesChemical synaptic transmissionSystematic literature searchEnvironmental factorsCurrent knowledge gapsPotential roleOrexin pathwayPathwayBrain alterationsPeripheral tissues
2022
Genetically regulated multi-omics study for symptom clusters of posttraumatic stress disorder highlights pleiotropy with hematologic and cardio-metabolic traits
Pathak GA, Singh K, Wendt FR, Fleming TW, Overstreet C, Koller D, Tylee DS, De Angelis F, Cabrera Mendoza B, Levey DF, Koenen KC, Krystal JH, Pietrzak RH, O’ Donell C, Gaziano JM, Falcone G, Stein MB, Gelernter J, Pasaniuc B, Mancuso N, Davis LK, Polimanti R. Genetically regulated multi-omics study for symptom clusters of posttraumatic stress disorder highlights pleiotropy with hematologic and cardio-metabolic traits. Molecular Psychiatry 2022, 27: 1394-1404. PMID: 35241783, PMCID: PMC9210390, DOI: 10.1038/s41380-022-01488-9.Peer-Reviewed Original ResearchConceptsLocal genetic correlationsCell type-specific expressionVanderbilt University biorepositoryMulti-omics studiesMulti-omics investigationsDorsolateral prefrontal cortex tissueGenomic evidenceLaboratory traitsSpecific expressionCardio-metabolic traitsMillion Veteran ProgramPrefrontal cortex tissueMiR-148GenesGenetic correlationsRegulatory profileTraitsProtein expressionCardiometabolic traitsExpressionVeteran ProgramCortex tissueBiological heterogeneitySplicingPrioritization approach
2021
Sex-stratified gene-by-environment genome-wide interaction study of trauma, posttraumatic-stress, and suicidality
Wendt FR, Pathak GA, Levey DF, Nuñez YZ, Overstreet C, Tyrrell C, Adhikari K, De Angelis F, Tylee DS, Goswami A, Krystal JH, Abdallah CG, Stein MB, Kranzler HR, Gelernter J, Polimanti R. Sex-stratified gene-by-environment genome-wide interaction study of trauma, posttraumatic-stress, and suicidality. Neurobiology Of Stress 2021, 14: 100309. PMID: 33665242, PMCID: PMC7905234, DOI: 10.1016/j.ynstr.2021.100309.Peer-Reviewed Original ResearchGenome-wide interaction studyRisk lociChromatin interaction profilesExtracellular matrix biologyGene-based analysisMatrix biologyMolecular basisTranscriptomic profilesInteraction studiesMultivariate geneGenetic perspectiveSNP effectsSuicidal behavior severityLociNovel targetGenesInteraction profilesSynaptic plasticityCellsInteractorsGenetic riskBiologyStressGxEIndependent cohort
2020
Single-cell Transcriptome Mapping Identifies Common and Cell-type Specific Genes Affected by Acute Delta9-tetrahydrocannabinol in Humans
Hu Y, Ranganathan M, Shu C, Liang X, Ganesh S, Osafo-Addo A, Yan C, Zhang X, Aouizerat BE, Krystal JH, D’Souza D, Xu K. Single-cell Transcriptome Mapping Identifies Common and Cell-type Specific Genes Affected by Acute Delta9-tetrahydrocannabinol in Humans. Scientific Reports 2020, 10: 3450. PMID: 32103029, PMCID: PMC7044203, DOI: 10.1038/s41598-020-59827-1.Peer-Reviewed Original ResearchConceptsSpecific genesCell type-specific genesGene expressionSingle-cell transcriptomic profilingCell typesGene expression correlationsAlters gene expressionTranscriptome mappingTranscriptomic profilingExpression correlationEnrichment analysisCommon genesImportant medical implicationsSignificant genesGenesMajor immune cell typesCell proliferationImmune cell typesImmune responseCell toxicityMedical implicationsCellsImportant insightsExpressionHuman immune cells
2019
Epigenome‐Wide DNA Methylation Association Analysis Identified Novel Loci in Peripheral Cells for Alcohol Consumption Among European American Male Veterans
Xu K, Montalvo‐Ortiz J, Zhang X, Southwick SM, Krystal JH, Pietrzak RH, Gelernter J. Epigenome‐Wide DNA Methylation Association Analysis Identified Novel Loci in Peripheral Cells for Alcohol Consumption Among European American Male Veterans. Alcohol Clinical And Experimental Research 2019, 43: 2111-2121. PMID: 31386212, PMCID: PMC9377208, DOI: 10.1111/acer.14168.Peer-Reviewed Original ResearchConceptsEpigenome-wide association studiesDNA methylationCpG sitesSignificant CpG sitesHigh-density methylation arraysNovel DNA methylation sitesNew CpG sitesDNA methylation sitesEpigenome-wide DNA methylationAmino acid transportIndividual CpG sitesGene lengthPeripheral cellsNovel lociDNA sitesKEGG databaseMethylation sitesEnrichment analysisMethylation arraysAssociation studiesAssociation analysisGenesMethylationAcid transportFalse discovery rate
2018
Genome-wide association study identifies glutamate ionotropic receptor GRIA4 as a risk gene for comorbid nicotine dependence and major depression
Zhou H, Cheng Z, Bass N, Krystal JH, Farrer LA, Kranzler HR, Gelernter J. Genome-wide association study identifies glutamate ionotropic receptor GRIA4 as a risk gene for comorbid nicotine dependence and major depression. Translational Psychiatry 2018, 8: 208. PMID: 30287806, PMCID: PMC6172277, DOI: 10.1038/s41398-018-0258-8.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesGenome-wide association study identifiesRisk genesTop risk genesCalcium ion bindingGenomes reference panelFast excitatory synaptic transmissionGenetic risk variantsGenetic basisEnrichment analysisAssociation studiesExome arrayCell adhesionRisk variantsGenesReference panelGenetic riskAMPA-sensitive glutamate receptorsIntronic variantsIon bindingBiological mechanismsConditional analysisGRIA4Excitatory synaptic transmissionSynaptic transmissionF131. Genome-Wide Association Study Identifies Glutamate Ionotropic Receptor GRIA4 as a Risk Gene for Comorbid Nicotine Dependence and Major Depression
Zhou H, Zhong Z, Bass N, Krystal J, Farrer L, Kranzler H, Gelernter J. F131. Genome-Wide Association Study Identifies Glutamate Ionotropic Receptor GRIA4 as a Risk Gene for Comorbid Nicotine Dependence and Major Depression. Biological Psychiatry 2018, 83: s288-s289. DOI: 10.1016/j.biopsych.2018.02.744.Peer-Reviewed Original Research
2016
Implication of NOTCH1 gene in susceptibility to anxiety and depression among sexual abuse victims
Steine IM, Zayats T, Stansberg C, Pallesen S, Mrdalj J, Håvik B, Soulé J, Haavik J, Milde AM, Skrede S, Murison R, Krystal J, Grønli J. Implication of NOTCH1 gene in susceptibility to anxiety and depression among sexual abuse victims. Translational Psychiatry 2016, 6: e977-e977. PMID: 27959334, PMCID: PMC5290341, DOI: 10.1038/tp.2016.248.Peer-Reviewed Original ResearchMeSH KeywordsAllelesAnimalsAnxiety DisordersBrainDepressive DisorderDisease Models, AnimalFemaleGene ExpressionGenetic Predisposition to DiseaseHumansLife Change EventsMaleNeurodevelopmental DisordersPolymorphism, Single NucleotideRats, WistarReceptor, Notch1Sex OffensesTranslational Research, BiomedicalConceptsSingle nucleotide polymorphismsDifferent early-life conditionsGene expressionEarly-life conditionsBrain gene expressionGenetic association studiesCandidate genesAssociation studiesNeural developmentDifferential expressionTag single nucleotide polymorphismsBrain of rodentsGenesHuman samplesFalse discovery rateNotch1 geneSymptoms of anxietyExpressionSignificance analysisDiscovery ratePotential importanceEarly life stressMeans of correspondencePotential relevancePlk5
2015
Gene-based and pathway-based genome-wide association study of alcohol dependence
Lingjun Z, ZHANG CK, SAYWARD FG, CHEUNG KH, Kesheng W, KRYSTAL JH, Hongyu Z, Xingguang L. Gene-based and pathway-based genome-wide association study of alcohol dependence. General Psychiatry 2015, 27: 111-118. PMID: 26120261, PMCID: PMC4466852, DOI: 10.11919/j.issn.1002-0829.215031.Peer-Reviewed Original ResearchGenome-wide association studiesRisk genesAssociation studiesBiological signaling processesPXN geneGene pathwaysSignaling processesGlycan degradationInteraction pathwayGenetic markersTransporter pathwaysGenesDiscovery samplePathwayReplication sampleAfrican American casesRisk pathwaysMultiple testingBonferroni correctionNew evidence
2013
Exome-wide association study of replicable nonsynonymous variants conferring risk for alcohol dependence.
Zuo L, Saba L, Wang K, Zhang X, Krystal JH, Tabakoff B, Luo X. Exome-wide association study of replicable nonsynonymous variants conferring risk for alcohol dependence. Journal Of Studies On Alcohol And Drugs 2013, 74: 622-5. PMID: 23739027, PMCID: PMC3711352, DOI: 10.15288/jsad.2013.74.622.Peer-Reviewed Original ResearchConceptsApolipoprotein E receptor 2Risk genesNonsynonymous variantsRNA expression analysisExome-wide association studyE receptor 2Expression analysisAssociation studiesGenesWhole exomeProtein 2RNA expressionNsSNPReplicable associationsAlcohol dependenceNonhuman speciesEuropean American sampleReceptor 2UbiquitinVariantsMultiple testingSpeciesExomeBioinformaticsUBAP2NKAIN1–SERINC2 is a functional, replicable and genome-wide significant risk gene region specific for alcohol dependence in subjects of European descent
Zuo L, Wang K, Zhang XY, Krystal JH, Li CS, Zhang F, Zhang H, Luo X. NKAIN1–SERINC2 is a functional, replicable and genome-wide significant risk gene region specific for alcohol dependence in subjects of European descent. Drug And Alcohol Dependence 2013, 129: 254-264. PMID: 23455491, PMCID: PMC3628730, DOI: 10.1016/j.drugalcdep.2013.02.006.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesExpression quantitative loci (eQTL) analysisGene regionMetabolic pathwaysQuantitative loci analysisSNP-expression associationsCis-acting regulatory effectsDiscovery sampleSNP-disease associationsNumerous genesReplication sampleLocus analysisAssociation studiesAssociation analysisRisk SNPsTranscript expressionSNPsRegulatory effectsGenesPathwayEuropean descentExpression
2012
Genome‐wide search for replicable risk gene regions in alcohol and nicotine co‐dependence
Zuo L, Zhang F, Zhang H, Zhang X, Wang F, Li C, Lu L, Hong J, Lu L, Krystal J, Deng H, Luo X. Genome‐wide search for replicable risk gene regions in alcohol and nicotine co‐dependence. American Journal Of Medical Genetics Part B Neuropsychiatric Genetics 2012, 159B: 437-444. PMID: 22488850, PMCID: PMC3405545, DOI: 10.1002/ajmg.b.32047.Peer-Reviewed Original ResearchConceptsChromosome 3Genome-wide false discovery rateGene regionFalse discovery rateGenome-wide association analysisExpression quantitative trait loci (eQTL) analysisQuantitative trait locus (QTL) analysisRisk SNPsTranscript expressionGenome-wide association strategyGenome-wide searchCombined P valueSNP-disease associationsAssociation peakGenomic regionsEQTL analysisEuropean American casesCausal lociLocus analysisGene expressionAssociation analysisGenesSNPsRegulatory effectsDiscovery rate
2006
Mutation screen of the GAD2 gene and association study of alcoholism in three populations
Lappalainen J, Krupitsky E, Kranzler HR, Luo X, Remizov M, Pchelina S, Taraskina A, Zvartau E, Räsanen P, Makikyro T, Somberg LK, Krystal JH, Stein MB, Gelernter J. Mutation screen of the GAD2 gene and association study of alcoholism in three populations. American Journal Of Medical Genetics Part B Neuropsychiatric Genetics 2006, 144B: 183-192. PMID: 17034009, DOI: 10.1002/ajmg.b.30377.Peer-Reviewed Original ResearchMeSH KeywordsAdultAlcoholismBlack or African AmericanCase-Control StudiesDNA Mutational AnalysisExonsFemaleGene FrequencyGenetic Predisposition to DiseaseGenetic TestingGlutamate DecarboxylaseHispanic or LatinoHumansIsoenzymesLinkage DisequilibriumMaleMutationPolymorphism, Single NucleotideStudentsUnited StatesWhite PeopleConceptsSingle nucleotide polymorphismsGAD2 geneNon-synonymous polymorphismsAssociation studiesSequence variantsGamma-amino butyric acidGlutamate decarboxylase 2GenesMutation screenNucleotide polymorphismsAdditional populationsMajor enzymeG single nucleotide polymorphismPolymorphismG variantButyric acidPopulationVariantsEnzymeAdditional samplesRoleRussian malesVariationScreenDHPLC
2004
Confirmation and fine mapping of the chromosome 1 alcohol dependence risk locus
Lappalainen J, Kranzler HR, Petrakis I, Somberg LK, Page G, Krystal JH, Gelernter J. Confirmation and fine mapping of the chromosome 1 alcohol dependence risk locus. Molecular Psychiatry 2004, 9: 312-319. PMID: 15094791, DOI: 10.1038/sj.mp.4001429.Peer-Reviewed Original ResearchConceptsTransmission disequilibrium testNovel candidate genesSTR markersTransmission disequilibriumShort tandem repeat markersGenetic linkage studiesFine mappingRepeat markersTandem repeat markersCandidate genesChromosome 1Linkage signalMap intervalSmall nuclear familiesBase pairsGenesLinkage disequilibriumLinkage findingsSusceptibility genesDNA base pairsLinkage studiesSupport intervalBP intervalChromosome 1pDisequilibrium test