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 GroupsPositive personality traits moderate persistent high alcohol consumption, determined by polygenic risk in U.S. military veterans: results from a 10-year, population-based, observational cohort study
Na P, Zhou H, Montalvo-Ortiz J, Cabrera-Mendoza B, Petrakis I, Krystal J, Polimanti R, Gelernter J, Pietrzak R. Positive personality traits moderate persistent high alcohol consumption, determined by polygenic risk in U.S. military veterans: results from a 10-year, population-based, observational cohort study. Psychological Medicine 2023, 53: 7893-7901. PMID: 37642191, DOI: 10.1017/s003329172300199x.Peer-Reviewed Original ResearchMeSH KeywordsAlcohol DrinkingCohort StudiesGenome-Wide Association StudyHumansLongitudinal StudiesPersonalityVeterans
2022
Genetic liability to suicidal thoughts and behaviors and risk of suicide attempt in US military veterans: moderating effects of cumulative trauma burden
Nichter B, Koller D, De Angelis F, Wang J, Girgenti M, Na P, Hill M, Norman S, Krystal J, Gelernter J, Polimanti R, Pietrzak R. Genetic liability to suicidal thoughts and behaviors and risk of suicide attempt in US military veterans: moderating effects of cumulative trauma burden. Psychological Medicine 2022, 53: 6325-6333. PMID: 36444557, DOI: 10.1017/s0033291722003646.Peer-Reviewed Original ResearchMeSH KeywordsFemaleGenome-Wide Association StudyHumansMaleRisk FactorsSuicidal IdeationSuicide, AttemptedVeteransConceptsPolygenic risk scoresUS military veteransLifetime suicide attemptsSuicide attemptsTrauma exposureTrauma burdenGenetic liabilityMilitary veteransDrug repurposing analysisPopulation-based sampleCumulative trauma exposureLifetime trauma exposureLow trauma exposureSuicide prediction modelsChronic inflammationInflammatory processNervous system developmentRisk scorePsychiatric characteristicsSuicidal behaviorExposure interactionsLarge genome-wide association studiesHigh levelsVeteransSuicidalitySex-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 ResearchMeSH KeywordsDNA MethylationEpigenomeGenome-Wide Association StudyHumansMaleStress Disorders, Post-TraumaticVeteransConceptsEpigenome-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
2021
Psychosocial moderators of polygenic risk for suicidal ideation: Results from a 7-year population-based, prospective cohort study of U.S. veterans
Na PJ, De Angelis F, Nichter B, Wendt FR, Krystal JH, Southwick SM, Levey DF, Gelernter J, Polimanti R, Pietrzak RH. Psychosocial moderators of polygenic risk for suicidal ideation: Results from a 7-year population-based, prospective cohort study of U.S. veterans. Molecular Psychiatry 2021, 27: 1068-1074. PMID: 34725455, DOI: 10.1038/s41380-021-01352-2.Peer-Reviewed Original ResearchMeSH KeywordsCohort StudiesGenome-Wide Association StudyHumansProspective StudiesSuicidal IdeationVeteransConceptsNew-onset suicidal ideationChronic suicidal ideationPolygenic risk scoresSuicidal ideationProspective cohort studyPolygenic riskRisk of SIHigher baseline levelsHigh polygenic riskModifiable psychosocial factorsSocial supportDispositional optimismCohort studyProspective cohortUS veteransSymptomatic courseRisk scorePsychosocial factorsGenome-wide association studiesBaseline levelsU.S. veteransSuicidal thoughtsPsychosocial moderatorsStudy periodLarge genome-wide association studiesAttachment Style Moderates Polygenic Risk for Incident Posttraumatic Stress in U.S. Military Veterans: A 7-Year, Nationally Representative, Prospective Cohort Study
Tamman AJF, Wendt FR, Pathak GA, Krystal JH, Southwick SM, Sippel LM, Gelernter J, Polimanti R, Pietrzak RH. Attachment Style Moderates Polygenic Risk for Incident Posttraumatic Stress in U.S. Military Veterans: A 7-Year, Nationally Representative, Prospective Cohort Study. Biological Psychiatry 2021, 91: 637-646. PMID: 34955171, DOI: 10.1016/j.biopsych.2021.09.025.Peer-Reviewed Original ResearchMeSH KeywordsGenome-Wide Association StudyHumansMilitary PersonnelMultifactorial InheritanceProspective StudiesStress Disorders, Post-TraumaticVeteransConceptsPosttraumatic stress disorderAttachment styleU.S. military veteransIncident posttraumatic stress disorderSocial environmental factorsDevelopment of PTSDMilitary veteransInsecure attachment stylesSecure attachment stylePolygenic riskEffect of PRSLifetime trauma burdenPTSD preventionPosttraumatic stressPTSD developmentPTSD symptomsStress disorderPolygenic risk scoresHigh polygenic riskProspective designNationally RepresentativePotential pharmacotherapyMultivariate geneStyleVeterans
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 tissueDivergenceMultivariate genome-wide analysis of education, socioeconomic status and brain phenome
Wendt FR, Pathak GA, Lencz T, Krystal JH, Gelernter J, Polimanti R. Multivariate genome-wide analysis of education, socioeconomic status and brain phenome. Nature Human Behaviour 2020, 5: 482-496. PMID: 33349686, PMCID: PMC8068566, DOI: 10.1038/s41562-020-00980-y.Peer-Reviewed Original ResearchMeSH KeywordsEducational StatusGenome-Wide Association StudyHumansIntelligenceMental DisordersPsychopathologyRisk FactorsSocial ClassConceptsPsychosocial factorsSocioeconomic statusPsychiatric disordersBipolar disorderGenetic riskNeuronal cell typesMajor depressionTourette syndromeBrain morphologyDisordersImaging phenotypesCell typesRisky behaviorsPsychopathologyGenetic overlapRiskGenetic discoveriesPsychiatric traitsStatusSyndromeAttachment Style Moderates Polygenic Risk for Posttraumatic Stress in United States Military Veterans: Results From the National Health and Resilience in Veterans Study
Tamman AJF, Wendt FR, Pathak GA, Krystal JH, Montalvo-Ortiz JL, Southwick SM, Sippel LM, Gelernter J, Polimanti R, Pietrzak RH. Attachment Style Moderates Polygenic Risk for Posttraumatic Stress in United States Military Veterans: Results From the National Health and Resilience in Veterans Study. Biological Psychiatry 2020, 89: 878-887. PMID: 33276944, DOI: 10.1016/j.biopsych.2020.09.018.Peer-Reviewed Original ResearchGenome-Wide Association StudyHumansMultifactorial InheritanceStress Disorders, Post-TraumaticUnited StatesVeteransWhite People
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
Machine learning selected smoking-associated DNA methylation signatures that predict HIV prognosis and mortality
Zhang X, Hu Y, Aouizerat BE, Peng G, Marconi VC, Corley MJ, Hulgan T, Bryant KJ, Zhao H, Krystal JH, Justice AC, Xu K. Machine learning selected smoking-associated DNA methylation signatures that predict HIV prognosis and mortality. Clinical Epigenetics 2018, 10: 155. PMID: 30545403, PMCID: PMC6293604, DOI: 10.1186/s13148-018-0591-z.Peer-Reviewed Original ResearchMeSH KeywordsAdultCpG IslandsDNA MethylationEpigenesis, GeneticFemaleFrailtyGenome-Wide Association StudyHIV InfectionsHumansMachine LearningMaleMiddle AgedMortalityPrognosisSignal TransductionSmokingConceptsWhite blood cellsSmoking-associated DNA methylationHIV prognosisInfection-related clinical outcomesBlood cellsSmoking-associated CpGsHIV-positive individualsImmune-related outcomesEpigenome-wide significant CpGsClinical outcomesTobacco smokingVeteran populationSurvival rateDNA methylation indexMortalityFrailtyHIVMethylation indexPrognosisMethylation signaturesDNA methylationOutcomesCell cycleCpGSignificant CpGsGenome-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
DNA methylation signatures of illicit drug injection and hepatitis C are associated with HIV frailty
Zhang X, Hu Y, Justice AC, Li B, Wang Z, Zhao H, Krystal JH, Xu K. DNA methylation signatures of illicit drug injection and hepatitis C are associated with HIV frailty. Nature Communications 2017, 8: 2243. PMID: 29269866, PMCID: PMC5740109, DOI: 10.1038/s41467-017-02326-1.Peer-Reviewed Original ResearchConceptsIllicit drug injectionHepatitis C infectionWhite blood cellsIllicit drug useCo-occurring conditionsMethylation signaturesDiscovery sampleC infectionHepatitis CEpigenome-wide association analysisLower frailtyDrug injectionHigh frailtyImmune functionHealth outcomesDrug useFrailtyDNA methylation signaturesBlood cellsHIVReplication sampleEpigenetic programmingSignificant CpGsEpigenetic effectsIndividualsPolygenic 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 disorderOxytocin receptor gene polymorphisms, attachment, and PTSD: Results from the National Health and Resilience in Veterans Study
Sippel LM, Han S, Watkins LE, Harpaz-Rotem I, Southwick SM, Krystal JH, Olff M, Sherva R, Farrer LA, Kranzler HR, Gelernter J, Pietrzak RH. Oxytocin receptor gene polymorphisms, attachment, and PTSD: Results from the National Health and Resilience in Veterans Study. Journal Of Psychiatric Research 2017, 94: 139-147. PMID: 28715704, PMCID: PMC5605420, DOI: 10.1016/j.jpsychires.2017.07.008.Peer-Reviewed Original Research
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 ResearchMeSH KeywordsAlcoholismAnimalsAustraliaCohort StudiesEuropeGenome-Wide Association StudyHumansMicePolymorphism, Single NucleotideRatsRisk FactorsWhite PeopleConceptsAfrican 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 analysis
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 ResearchRare SERINC2 variants are specific for alcohol dependence in individuals of European descent
Zuo L, Wang KS, Zhang XY, Li CS, Zhang F, Wang X, Chen W, Gao G, Zhang H, Krystal JH, Luo X. Rare SERINC2 variants are specific for alcohol dependence in individuals of European descent. Pharmacogenetics And Genomics 2013, 23: 395-402. PMID: 23778322, PMCID: PMC4287355, DOI: 10.1097/fpc.0b013e328362f9f2.Peer-Reviewed Original ResearchNKAIN1–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