2023
Multi-ancestry study of the genetics of problematic alcohol use in over 1 million individuals
Zhou H, Kember R, Deak J, Xu H, Toikumo S, Yuan K, Lind P, Farajzadeh L, Wang L, Hatoum A, Johnson J, Lee H, Mallard T, Xu J, Johnston K, Johnson E, Nielsen T, Galimberti M, Dao C, Levey D, Overstreet C, Byrne E, Gillespie N, Gordon S, Hickie I, Whitfield J, Xu K, Zhao H, Huckins L, Davis L, Sanchez-Roige S, Madden P, Heath A, Medland S, Martin N, Ge T, Smoller J, Hougaard D, Børglum A, Demontis D, Krystal J, Gaziano J, Edenberg H, Agrawal A, Justice A, Stein M, Kranzler H, Gelernter J. Multi-ancestry study of the genetics of problematic alcohol use in over 1 million individuals. Nature Medicine 2023, 29: 3184-3192. PMID: 38062264, PMCID: PMC10719093, DOI: 10.1038/s41591-023-02653-5.Peer-Reviewed Original ResearchAlcoholismGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansPhenotypePolymorphism, Single NucleotideRacial Groups
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 ResearchMeSH KeywordsFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHSP27 Heat-Shock ProteinsHumansMaleMental DisordersNeuroticismPhenotypePolymorphism, Single NucleotideTranscription FactorsTranscriptomeConceptsGenome-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 riskNCOA6GeneticsHeritabilityPathwayFemales
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
Apolipoprotein E gene polymorphism, posttraumatic stress disorder, and cognitive function in older U.S. veterans: Results from the National Health and Resilience in Veterans Study
Averill LA, Abdallah CG, Levey DF, Han S, Harpaz‐Rotem I, Kranzler HR, Southwick SM, Krystal JH, Gelernter J, Pietrzak RH. Apolipoprotein E gene polymorphism, posttraumatic stress disorder, and cognitive function in older U.S. veterans: Results from the National Health and Resilience in Veterans Study. Depression And Anxiety 2019, 36: 834-845. PMID: 31385647, DOI: 10.1002/da.22912.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderExecutive functionCognitive functioningStress disorderΕ4 carrier statusΕ4 carriersVeterans StudyCognitive dysfunctionAttention/concentrationGreater cognitive difficultiesLower cognitive functioningOlder U.S. veteransΕ4 allele carrier statusPerseverative errorsCognitive difficultiesReplication sampleCarrier statusCognitive functionImportance of assessingNational HealthCognitive declinePredictive effectApolipoprotein E gene polymorphismE gene polymorphismΕ4 allele carriersAltered functional connectivity and low-frequency signal fluctuations in early psychosis and genetic high risk
Tang Y, Zhou Q, Chang M, Chekroud A, Gueorguieva R, Jiang X, Zhou Y, He G, Rowland M, Wang D, Fu S, Yin Z, Leng H, Wei S, Xu K, Wang F, Krystal JH, Driesen NR. Altered functional connectivity and low-frequency signal fluctuations in early psychosis and genetic high risk. Schizophrenia Research 2019, 210: 172-179. PMID: 30685394, DOI: 10.1016/j.schres.2018.12.041.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultCerebral CortexConnectomeFemaleGenetic Predisposition to DiseaseHumansMagnetic Resonance ImagingMalePsychotic DisordersRiskSchizophreniaYoung AdultConceptsFunctional connectivityHigh-risk individualsAltered functional connectivityHealthy comparison subjectsGenetic high riskGenetic high-risk individualsLow-frequency signal fluctuationsFunctional magnetic resonanceALFF abnormalitiesALFF measuresFunctional connectivity measuresBasal gangliaFirst episodeHigh riskEarly psychosisComparison subjectsSchizophrenia diathesisSchizophrenia vulnerabilityFESzGenetic riskLow-frequency fluctuationsIllnessSchizophreniaVoxel connectivityGHR
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
2017
Polygenic Scores for Major Depressive Disorder and Risk of Alcohol Dependence
Andersen AM, Pietrzak RH, Kranzler HR, Ma L, Zhou H, Liu X, Kramer J, Kuperman S, Edenberg HJ, Nurnberger JI, Rice JP, Tischfield JA, Goate A, Foroud TM, Meyers JL, Porjesz B, Dick DM, Hesselbrock V, Boerwinkle E, Southwick SM, Krystal JH, Weissman MM, Levinson DF, Potash JB, Gelernter J, Han S. Polygenic Scores for Major Depressive Disorder and Risk of Alcohol Dependence. JAMA Psychiatry 2017, 74: 1153-1160. PMID: 28813562, PMCID: PMC5710224, DOI: 10.1001/jamapsychiatry.2017.2269.Peer-Reviewed Original ResearchMeSH KeywordsAdultAlcoholismComorbidityDepressive Disorder, MajorFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMaleMiddle AgedMultifactorial InheritanceUnited StatesWhite PeopleConceptsMDD polygenic risk scoresMajor depressive disorderPolygenic risk scoresAlcohol dependenceDepressive disorderSignificant public health burdenPublic health burdenAD comorbidityNational HealthHealth burdenMAIN OUTCOMECase-control statusRisk scoreRisk of ADVeterans StudyYale-PennGenetic susceptibilityMDD statusCommon genetic factorsSubstance dependenceMDD casesAD samplesPolygenic riskGenetic factorsHeritable disorderAssociation Between Functional Polymorphism in Neuropeptide Y Gene Promoter rs16147 and Resilience to Traumatic Stress in US Military Veterans.
Watkins LE, Han S, Krystal JH, Southwick SM, Gelernter J, Pietrzak RH. Association Between Functional Polymorphism in Neuropeptide Y Gene Promoter rs16147 and Resilience to Traumatic Stress in US Military Veterans. The Journal Of Clinical Psychiatry 2017, 78: e1058-e1059. PMID: 29099554, DOI: 10.4088/jcp.17l11646.Peer-Reviewed Original ResearchAttachment style moderates effects of FKBP5 polymorphisms and childhood abuse on post-traumatic stress symptoms: Results from the National Health and Resilience in Veterans Study
Tamman AJF, Sippel LM, Han S, Neria Y, Krystal JH, Southwick SM, Gelernter J, Pietrzak RH. Attachment style moderates effects of FKBP5 polymorphisms and childhood abuse on post-traumatic stress symptoms: Results from the National Health and Resilience in Veterans Study. The World Journal Of Biological Psychiatry 2017, 20: 289-300. PMID: 28891785, DOI: 10.1080/15622975.2017.1376114.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 relevancePlk5FKBP5 polymorphisms, childhood abuse, and PTSD symptoms: Results from the National Health and Resilience in Veterans Study
Watkins LE, Han S, Harpaz-Rotem I, Mota NP, Southwick SM, Krystal JH, Gelernter J, Pietrzak RH. FKBP5 polymorphisms, childhood abuse, and PTSD symptoms: Results from the National Health and Resilience in Veterans Study. Psychoneuroendocrinology 2016, 69: 98-105. PMID: 27078785, DOI: 10.1016/j.psyneuen.2016.04.001.Peer-Reviewed Original ResearchAdultAllelesChildChild AbuseGene-Environment InteractionGenetic Predisposition to DiseaseGenotypeHumansHypothalamo-Hypophyseal SystemLinkage DisequilibriumMalePituitary-Adrenal SystemPolymorphism, Single NucleotideRisk FactorsStress Disorders, Post-TraumaticSubstance-Related DisordersTacrolimus Binding ProteinsVeterans
2015
Familial Alcoholism Risk and the Ratio of Stimulant to Sedative Effects of Ketamine
Yoon G, Pittman B, Limoncelli D, Krystal JH, Petrakis IL. Familial Alcoholism Risk and the Ratio of Stimulant to Sedative Effects of Ketamine. Biological Psychiatry 2015, 79: e69-e70. PMID: 26475672, DOI: 10.1016/j.biopsych.2015.09.006.Peer-Reviewed Original ResearchSignificant association between rare IPO11‐HTR1A variants and attention deficit hyperactivity disorder in Caucasians
Zuo L, Saba L, Lin X, Tan Y, Wang K, Krystal JH, Tabakoff B, Luo X. Significant association between rare IPO11‐HTR1A variants and attention deficit hyperactivity disorder in Caucasians. American Journal Of Medical Genetics Part B Neuropsychiatric Genetics 2015, 168: 544-556. PMID: 26079129, PMCID: PMC4851708, DOI: 10.1002/ajmg.b.32329.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAttention Deficit Disorder with HyperactivityBeta KaryopherinsBlack or African AmericanFemaleGene FrequencyGenetic Predisposition to DiseaseGenetic VariationHumansMaleMiddle AgedPolymorphism, Single NucleotideQuantitative Trait LociReceptor, Serotonin, 5-HT1ARisk FactorsWhite PeopleConceptsAttention deficit hyperactivity disorderDeficit hyperactivity disorderNeuropsychiatric disordersRare variantsHyperactivity disorderDifferent neuropsychiatric disordersRNA expression changesIndependent cohortSignificant associationSignificant regulatory effectDisordersCaucasiansEuropean descentRegulatory effectsHuman brainDiseaseAssociationCis-eQTL analysisIPO11African descentExpression changesSubjectsCohortFalse discovery rateVariants
2013
Sex chromosome-wide association analysis suggested male-specific risk genes for alcohol dependence
Zuo L, Wang K, Zhang X, Pan X, Wang G, Krystal JH, Zhang H, Luo X. Sex chromosome-wide association analysis suggested male-specific risk genes for alcohol dependence. Psychiatric Genetics 2013, 23: 233-238. PMID: 23907288, PMCID: PMC3941913, DOI: 10.1097/ypg.0b013e328364b8c7.Peer-Reviewed Original ResearchExome-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 ResearchMeSH KeywordsAdultAlcoholismCarrier ProteinsCase-Control StudiesFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMaleMembrane ProteinsMiddle AgedWhite PeopleConceptsGenome-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 Significant Association Signals in IPO11‐HTR1A Region Specific for Alcohol and Nicotine Codependence
Zuo L, Zhang X, Wang F, Li C, Lu L, Ye L, Zhang H, Krystal JH, Deng H, Luo X. Genome‐Wide Significant Association Signals in IPO11‐HTR1A Region Specific for Alcohol and Nicotine Codependence. Alcohol Clinical And Experimental Research 2012, 37: 730-739. PMID: 23216389, PMCID: PMC3610804, DOI: 10.1111/acer.12032.Peer-Reviewed Original ResearchMeSH KeywordsAdultAlcoholismBeta KaryopherinsBlack or African AmericanCase-Control StudiesChromosomes, Human, Pair 5FemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyGenotypeHumansMaleMiddle AgedPolymorphism, Single NucleotideQuantitative Trait LociReceptor, Serotonin, 5-HT1ATobacco Use DisorderWhite PeopleConceptsGenome-wide significance levelSingle nucleotide polymorphismsReplication cohortDiscovery cohortAlcohol dependenceExpression quantitative loci (eQTL) analysisPeripheral blood mononuclear cell samplesNeuropsychiatric disordersWide significant association signalsMononuclear cell samplesGenome-wide association studiesQuantitative loci analysisGene-disease association analysisCis-eQTL analysisTop single nucleotide polymorphismsCis-acting regulatory effectsSignificant association signalsBrain tissue samplesAmerican controlsEuropean American controlsRisk single nucleotide polymorphismsAfrican-American controlsSevere subtypeGenomic regionsAfrican American casesGenome‐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
2011
A Novel, Functional and Replicable Risk Gene Region for Alcohol Dependence Identified by Genome-Wide Association Study
Zuo L, Zhang CK, Wang F, Li CS, Zhao H, Lu L, Zhang XY, Lu L, Zhang H, Zhang F, Krystal JH, Luo X. A Novel, Functional and Replicable Risk Gene Region for Alcohol Dependence Identified by Genome-Wide Association Study. PLOS ONE 2011, 6: e26726. PMID: 22096494, PMCID: PMC3210123, DOI: 10.1371/journal.pone.0026726.Peer-Reviewed Original ResearchGenome-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