2022
Sex-Specific Genetic and Transcriptomic Liability to Neuroticism
Wendt FR, Pathak GA, Singh K, Stein MB, Koenen KC, Krystal JH, Gelernter J, Davis LK, Polimanti R. Sex-Specific Genetic and Transcriptomic Liability to Neuroticism. Biological Psychiatry 2022, 93: 243-252. PMID: 36244801, PMCID: PMC10508260, DOI: 10.1016/j.biopsych.2022.07.019.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesTranscriptomic profilesAssociation studiesSingle nucleotide polymorphism heritabilityGene expression variationGenome-wide significanceSex-specific geneticChromosomal variationTranscriptomic changesRisk lociExpression variationBiological processesMolecular pathwaysLociPolygenic associationSex-specific effectsGenetic correlatesPolygenic scoresUK BiobankGenetic riskNCOA6GeneticsHeritabilityPathwayFemalesEpigenome-wide association study of posttraumatic stress disorder identifies novel loci in U.S. military veterans
Montalvo-Ortiz JL, Gelernter J, Cheng Z, Girgenti MJ, Xu K, Zhang X, Gopalan S, Zhou H, Duman RS, Southwick SM, Krystal JH, Pietrzak R. Epigenome-wide association study of posttraumatic stress disorder identifies novel loci in U.S. military veterans. Translational Psychiatry 2022, 12: 65. PMID: 35177594, PMCID: PMC8854688, DOI: 10.1038/s41398-022-01822-3.Peer-Reviewed Original ResearchConceptsEpigenome-wide association studiesAssociation studiesTranscription regulationCpG sitesGenome-wide association studiesCell type proportionsPosttraumatic stress disorderPotential epigenetic biomarkersSignificant CpG sitesEpigenetic mechanismsDNA methylationNovel lociCell signalingEpigenetic biomarkersMethylation analysisAxonal guidanceNovel molecular biomarkersEPIC BeadChipLifetime posttraumatic stress disorderMilitary veteransPostmortem brain tissueMedial orbitofrontal cortexMolecular biomarkersRegulationU.S. military veterans
2020
Transcriptomic organization of the human brain in post-traumatic stress disorder
Girgenti MJ, Wang J, Ji D, Cruz DA, Stein M, Gelernter J, Young K, Huber B, Williamson D, Friedman M, Krystal J, Zhao H, Duman R. Transcriptomic organization of the human brain in post-traumatic stress disorder. Nature Neuroscience 2020, 24: 24-33. PMID: 33349712, DOI: 10.1038/s41593-020-00748-7.Peer-Reviewed Original ResearchMeSH KeywordsAdultAutopsyBrain ChemistryCohort StudiesDepressive Disorder, MajorFemaleGene Expression RegulationGene Regulatory NetworksGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansInterneuronsMaleMiddle AgedNerve Tissue ProteinsSex CharacteristicsStress Disorders, Post-TraumaticTranscriptomeYoung AdultConceptsGenome-wide association studiesSignificant gene networksDifferential gene expressionSystems-level evidenceSignificant genetic liabilityMajor depressive disorder cohortGene networksTranscriptomic organizationTranscriptomic landscapeDownregulated setsGenomic networksGene expressionAssociation studiesMolecular determinantsExtensive remodelingGenotype dataSexual dimorphismSignificant divergenceMolecular profileNetwork analysisELFN1TranscriptsDimorphismPostmortem tissueDivergence
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 transmission
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 relevancePlk5Epigenome-wide differential DNA methylation between HIV-infected and uninfected individuals
Zhang X, Justice AC, Hu Y, Wang Z, Zhao H, Wang G, Johnson EO, Emu B, Sutton RE, Krystal JH, Xu K. Epigenome-wide differential DNA methylation between HIV-infected and uninfected individuals. Epigenetics 2016, 11: 750-760. PMID: 27672717, PMCID: PMC5094631, DOI: 10.1080/15592294.2016.1221569.Peer-Reviewed Original ResearchDifferential DNA methylationDNA methylationLarge-scale epigenome-wide association studyMajor histocompatibility complex (MHC) class I gene expressionNovel host genesEpigenome-wide association studiesClass I gene expressionVeterans Aging Cohort StudyEpigenome-wide significant CpGsEpigenetic controlHIV-1 infectionHost genesI gene expressionEpigenetic changesHost genomeCARD domainKey regulatorGene expressionAssociation studiesSignificant CpGsGene 5CpG sitesMethylationCell typesLower methylation
2015
A New Genomewide Association Meta‐Analysis of Alcohol Dependence
Zuo L, Tan Y, Zhang X, Wang X, Krystal J, Tabakoff B, Zhong C, Luo X. A New Genomewide Association Meta‐Analysis of Alcohol Dependence. Alcohol Clinical And Experimental Research 2015, 39: 1388-1395. PMID: 26173551, PMCID: PMC5587504, DOI: 10.1111/acer.12786.Peer-Reviewed Original ResearchConceptsAfrican American cohortAmerican cohortAlcohol dependenceSingle nucleotide polymorphismsAustralian cohortRisk genesEuropean American cohortRisk single nucleotide polymorphismsRat brainIndependent cohortMeta-AnalysisCohortMouse brainRisk variantsP-valueRNA expression analysisGenomewide association studiesBrainHuman tissuesNucleotide polymorphismsAssociation studiesGenomewide association analysisGene-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
2011
Erratum: Genome-Wide Association Study of Alcohol Dependence Implicates KIAA0040 on Chromosome 1q
Zuo L, Gelernter J, Zhang C, Zhao H, Lu L, Kranzler H, Malison R, Li C, Wang F, Zhang X, Deng H, Krystal J, Zhang F, Luo X. Erratum: Genome-Wide Association Study of Alcohol Dependence Implicates KIAA0040 on Chromosome 1q. Neuropsychopharmacology 2011, 37: 581-582. PMCID: PMC3242324, DOI: 10.1038/npp.2011.271.Peer-Reviewed Original ResearchGenome-wide association studiesAssociation studiesGenome-Wide Association Study of Alcohol Dependence Implicates KIAA0040 on Chromosome 1q
Zuo L, Gelernter J, Zhang CK, Zhao H, Lu L, Kranzler HR, Malison RT, Li CS, Wang F, Zhang XY, Deng HW, Krystal JH, Zhang F, Luo X. Genome-Wide Association Study of Alcohol Dependence Implicates KIAA0040 on Chromosome 1q. Neuropsychopharmacology 2011, 37: 557-566. PMID: 21956439, PMCID: PMC3242317, DOI: 10.1038/npp.2011.229.Peer-Reviewed Original ResearchConceptsSignificant risk genesHapMap populationsGenome-wide association analysisExpression quantitative trait loci (eQTL) analysisGenome-wide association study data setsQuantitative trait locus (QTL) analysisAssociation analysisMetabolic pathwaysRisk genesGenome-wide association studiesSNP-expression associationsCis-acting regulatory effectsExtracellular matrix proteinsGene expression levelsNumerous genesSignificant SNPsCausal variantsKIAA0040Risk lociRisk of ADLocus analysisAssociation studiesMatrix proteinsRisk SNPsCell migration
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