Featured Publications
Genome-wide association study of alcohol consumption and use disorder in 274,424 individuals from multiple populations
Kranzler HR, Zhou H, Kember RL, Vickers Smith R, Justice AC, Damrauer S, Tsao PS, Klarin D, Baras A, Reid J, Overton J, Rader DJ, Cheng Z, Tate JP, Becker WC, Concato J, Xu K, Polimanti R, Zhao H, Gelernter J. Genome-wide association study of alcohol consumption and use disorder in 274,424 individuals from multiple populations. Nature Communications 2019, 10: 1499. PMID: 30940813, PMCID: PMC6445072, DOI: 10.1038/s41467-019-09480-8.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesAssociation studiesMillion Veteran Program sampleGenetic correlationsWide significant lociSignificant genetic correlationsPolygenic risk scoresCell type groupSignificant lociHeritable traitEnrichment analysisTraitsMultiple populationsLociPhenotypeProgram samples
2024
Association patterns of antisocial personality disorder across substance use disorders
Low A, Stiltner B, Nunez Y, Adhikari K, Deak J, Pietrzak R, Kranzler H, Gelernter J, Polimanti R. Association patterns of antisocial personality disorder across substance use disorders. Translational Psychiatry 2024, 14: 346. PMID: 39198385, PMCID: PMC11358160, DOI: 10.1038/s41398-024-03054-z.Peer-Reviewed Original ResearchConceptsAntisocial personality disorderSubstance use disordersPersonality disorderUse disorderAssociation of antisocial personality disorderPresence of antisocial personality disorderPrevalence of antisocial personality disorderHazardous useDSM-5 SUD diagnosesSubstance use disorder severityDiagnostic criteriaInteraction effects with sexTobacco use disorderDSM-5Association of alcoholSUD diagnosisDisordersCocaineRacial/ethnic backgroundsIndividualsCocUDSeverityCannabisAssociation patternsAssociationGenome-wide association study of the common retinal disorder epiretinal membrane: Significant risk loci in each of three American populations
Gelernter J, Levey D, Galimberti M, Harrington K, Zhou H, Adhikari K, Gupta P, Program V, Gaziano J, Eliott D, Stein M. Genome-wide association study of the common retinal disorder epiretinal membrane: Significant risk loci in each of three American populations. Cell Genomics 2024, 4: 100582. PMID: 38870908, PMCID: PMC11228954, DOI: 10.1016/j.xgen.2024.100582.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesMillion Veteran ProgramRisk lociAssociation studiesTrans-ancestry meta-analysisSignificant risk lociPathway enrichment analysisEpiretinal membraneTrans-ancestryGenome-wideMultiple traitsGenetic associationEnrichment analysisGene expressionEuropean AmericansLoss of visual acuityVeteran ProgramGenetic correlationsLociBiological mechanismsAmerican populationVisual acuityRetinal conditionsControl individualsRetinal surface
2022
Associations between moderate alcohol consumption, brain iron, and cognition in UK Biobank participants: Observational and mendelian randomization analyses
Topiwala A, Wang C, Ebmeier KP, Burgess S, Bell S, Levey DF, Zhou H, McCracken C, Roca-Fernández A, Petersen SE, Raman B, Husain M, Gelernter J, Miller KL, Smith SM, Nichols TE. Associations between moderate alcohol consumption, brain iron, and cognition in UK Biobank participants: Observational and mendelian randomization analyses. PLOS Medicine 2022, 19: e1004039. PMID: 35834561, PMCID: PMC9282660, DOI: 10.1371/journal.pmed.1004039.Peer-Reviewed Original ResearchConceptsAlcohol use disorderHigh brain ironModerate alcohol consumptionBrain ironAlcohol consumptionAlcohol intakeUse disordersSubstantia nigraAlcohol-related cognitive declineIron depositionBrain regionsSusceptibility-weighted magnetic resonanceIron accumulationIron levelsBrain iron depositionBrain iron levelsSystemic iron levelsSystemic iron storesAlcohol-related cognitive deficitsBasal ganglia ironElevated liver ironMendelian randomizationWeekly alcohol consumptionUK Biobank participantsExecutive functionEffect of Pharmacogenomic Testing for Drug-Gene Interactions on Medication Selection and Remission of Symptoms in Major Depressive Disorder
Oslin DW, Lynch KG, Shih MC, Ingram EP, Wray LO, Chapman SR, Kranzler HR, Gelernter J, Pyne JM, Stone A, DuVall SL, Lehmann LS, Thase ME, Aslam M, Batki S, Bjork J, Blow F, Brenner L, Chen P, Desai S, Dieperink E, Fears S, Fuller M, Goodman C, Graham D, Haas G, Hamner M, Helstrom A, Hurley R, Icardi M, Jurjus G, Kilbourne A, Kreyenbuhl J, Lache D, Lieske S, Lynch J, Meyer L, Montalvo C, Muralidhar S, Ostacher M, Paschall G, Pfeiffer P, Prieto S, Przygodzki R, Ranganathan M, Rodriguez-Suarez M, Roggenkamp H, Schichman S, Schneeweis J, Simonetti J, Steinhauer S, Suppes T, Umbert M, Vassy J, Voora D, Wiechers I, Wood A. Effect of Pharmacogenomic Testing for Drug-Gene Interactions on Medication Selection and Remission of Symptoms in Major Depressive Disorder. JAMA 2022, 328: 151-161. PMID: 35819423, PMCID: PMC9277497, DOI: 10.1001/jama.2022.9805.Peer-Reviewed Original ResearchConceptsMajor depressive disorderPatient Health Questionnaire-9Usual care groupUsual carePharmacogenomic testingDrug-gene interactionsRemission rateMedication selectionCare groupDepressive disorderVeterans Affairs Medical CenterActive substance use disorderCo-primary outcomesPrescription of medicationsBetter clinical outcomesProportion of prescriptionsRemission of symptomsSubstance use disordersEligible patientsWeek 24Effective antidepressantSingle antidepressantClinical outcomesInitial treatmentQuestionnaire-9Post‐treatment effects of topiramate on alcohol‐related outcomes: A combined analysis of two placebo‐controlled trials
Kranzler HR, Feinn R, Pond T, Hartwell E, Gelernter J, Crist RC, Witkiewitz K. Post‐treatment effects of topiramate on alcohol‐related outcomes: A combined analysis of two placebo‐controlled trials. Addiction Biology 2022, 27: e13130. PMID: 35229945, PMCID: PMC9257958, DOI: 10.1111/adb.13130.Peer-Reviewed Original ResearchConceptsAlcohol use disorderPost-treatment periodAlcohol-related outcomesAlcohol-related problemsTopiramate's effectsSingle nucleotide polymorphismsPlacebo-controlled trialPrimary treatment outcomeOptimal treatment durationSelf-reported alcohol consumptionTrial of topiramatePost-treatment effectsTopiramate groupPlacebo groupSecond RCTMedication effectsTreatment outcomesProblematic alcohol useTopiramateTreatment durationUse disordersAlcohol consumptionΓ-glutamyltransferaseRobust effectGenotype groups
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 tissueDivergenceGenome-wide association study of smoking trajectory and meta-analysis of smoking status in 842,000 individuals
Xu K, Li B, McGinnis KA, Vickers-Smith R, Dao C, Sun N, Kember RL, Zhou H, Becker WC, Gelernter J, Kranzler HR, Zhao H, Justice AC. Genome-wide association study of smoking trajectory and meta-analysis of smoking status in 842,000 individuals. Nature Communications 2020, 11: 5302. PMID: 33082346, PMCID: PMC7598939, DOI: 10.1038/s41467-020-18489-3.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesLarge genome-wide association studiesMillion Veteran ProgramAssociation studiesExpression quantitative trait lociQuantitative trait lociChromatin interactionsComplex traitsFunctional annotationTrait lociSequencing ConsortiumDozen genesSignificant lociSmoking phenotypesLociMultiple populationsNew insightsPhenotypeVeteran ProgramGenetic vulnerabilityGenesTraitsAnnotationEuropean AmericansConsortiumAssociation of OPRM1 Functional Coding Variant With Opioid Use Disorder
Zhou H, Rentsch CT, Cheng Z, Kember RL, Nunez YZ, Sherva RM, Tate JP, Dao C, Xu K, Polimanti R, Farrer LA, Justice AC, Kranzler HR, Gelernter J. Association of OPRM1 Functional Coding Variant With Opioid Use Disorder. JAMA Psychiatry 2020, 77: 1072-1080. PMID: 32492095, PMCID: PMC7270886, DOI: 10.1001/jamapsychiatry.2020.1206.Peer-Reviewed Original ResearchConceptsOpioid use disorderUse disordersMendelian randomization analysisAfrican American individualsMAIN OUTCOMEFunctional coding variantSignificant associationCausal associationRandomization analysisElectronic health record dataCurrent opioid crisisAmerican individualsHealth record dataCognitive performanceInternational Statistical ClassificationRelated Health ProblemsPotential causal associationAmerican controlsEuropean American controlsAfrican-American controlsCoding variantBuprenorphine treatmentOUD diagnosisTobacco smokingNinth RevisionGenotyping Array Design and Data Quality Control in the Million Veteran Program
Hunter-Zinck H, Shi Y, Li M, Gorman BR, Ji SG, Sun N, Webster T, Liem A, Hsieh P, Devineni P, Karnam P, Gong X, Radhakrishnan L, Schmidt J, Assimes TL, Huang J, Pan C, Humphries D, Brophy M, Moser J, Muralidhar S, Huang GD, Przygodzki R, Concato J, Gaziano JM, Gelernter J, O’Donnell C, Hauser ER, Zhao H, O’Leary T, Program V, Tsao PS, Pyarajan S. Genotyping Array Design and Data Quality Control in the Million Veteran Program. American Journal Of Human Genetics 2020, 106: 535-548. PMID: 32243820, PMCID: PMC7118558, DOI: 10.1016/j.ajhg.2020.03.004.Peer-Reviewed Original ResearchConceptsMillion Veteran ProgramGenome-wide association studiesGenome-wide scanHigh-quality genotypesArray-based genotypingWhole-genome sequencingNon-European individualsAssociation studiesGenetic markersOmics assaysAxiom arrayDownstream analysisVeteran ProgramCommon variantsGenetic associationAfrican American ancestryAmerican ancestryMVP cohortRare variantsSingle assayDiversityFurther data releasesLarge biobanksPromising resourceQuality controlReproducible Genetic Risk Loci for Anxiety: Results From ∼200,000 Participants in the Million Veteran Program
Levey DF, Gelernter J, Polimanti R, Zhou H, Cheng Z, Aslan M, Quaden R, Concato J, Radhakrishnan K, Bryois J, Sullivan PF, Stein M. Reproducible Genetic Risk Loci for Anxiety: Results From ∼200,000 Participants in the Million Veteran Program. American Journal Of Psychiatry 2020, 177: 223-232. PMID: 31906708, PMCID: PMC7869502, DOI: 10.1176/appi.ajp.2019.19030256.Peer-Reviewed Original ResearchConceptsNovel genome-wide significant associationsGene expressionGenome-wide significant signalsGenome-wide significant associationMillion Veteran ProgramWide association studyGenetic risk lociSignificant genetic correlationsGenetic risk mechanismsGenetic architectureGlobal regulatorChromosome 3Risk lociChromosome 6Chromosome 7Association studiesLargest GWASLarge biobanksGlobal regulationGenetic correlationsContinuous traitsVeteran ProgramGWASsLociPrevious GWASsA genome-wide association study of cocaine use disorder accounting for phenotypic heterogeneity and gene–environment interaction
Sun J, Kranzler HR, Gelernter J, Bi J. A genome-wide association study of cocaine use disorder accounting for phenotypic heterogeneity and gene–environment interaction. Journal Of Psychiatry And Neuroscience 2020, 45: 34-44. PMID: 31490055, PMCID: PMC6919916, DOI: 10.1503/jpn.180098.Peer-Reviewed Original ResearchConceptsGenetic lociGenome-wide association testsPhenotypic heterogeneityNew genetic lociGenetic variantsWide association studyGene-environment interplayNovel genetic variantsHigh heritability estimatesSignificant genomeReplication sampleSingle nucleotide polymorphismsGenetic variationAssociation studiesLociNucleotide polymorphismsAssociation TestHeritability estimatesGene-environment interactionsReplication resultsCluster analysisEnvironmental factorsTRAK2GenomeDiscovery phase
2019
Genomewide Gene-by-Sex Interaction Scans Identify ADGRV1 for Sex Differences in Opioid Dependent African Americans
Yang BZ, Zhou H, Cheng Z, Kranzler HR, Gelernter J. Genomewide Gene-by-Sex Interaction Scans Identify ADGRV1 for Sex Differences in Opioid Dependent African Americans. Scientific Reports 2019, 9: 18070. PMID: 31792237, PMCID: PMC6889277, DOI: 10.1038/s41598-019-53560-0.Peer-Reviewed Original ResearchMeSH KeywordsAdultAllelesAnalgesics, OpioidBlack or African AmericanBrainCalcium-Binding ProteinsFemaleGene Expression ProfilingGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMaleMiddle AgedOpioid-Related DisordersPolymorphism, Single NucleotideReceptors, G-Protein-CoupledReceptors, Kainic AcidSex FactorsWhite PeopleConceptsOpioid dependenceOD riskSex-different effectsSex differencesInferior olivary nucleusDSM-IV diagnosisDimorphic riskSubstantia nigraAA menOlivary nucleusFrontal cortexEuropean-American subjectsADGRV1Further studiesRiskAfrican AmericansGenetic variantsDisease enrichment analysisBrainSex interactionNominal significanceMenFirst studyPutamenLungGenome-wide association study of alcohol dependence in male Han Chinese and cross-ethnic polygenic risk score comparison
Sun Y, Chang S, Wang F, Sun H, Ni Z, Yue W, Zhou H, Gelernter J, Malison RT, Kalayasiri R, Wu P, Lu L, Shi J. Genome-wide association study of alcohol dependence in male Han Chinese and cross-ethnic polygenic risk score comparison. Translational Psychiatry 2019, 9: 249. PMID: 31591379, PMCID: PMC6779867, DOI: 10.1038/s41398-019-0586-3.Peer-Reviewed Original ResearchAdultAlcohol DehydrogenaseAlcoholismAldehyde Dehydrogenase, MitochondrialAsian PeopleBlack or African AmericanCase-Control StudiesChinaCross-Cultural ComparisonGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansLogistic ModelsMaleMiddle AgedMultifactorial InheritancePolymorphism, Single NucleotideWhite PeopleYoung AdultEpigenome‐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 rateDifferentiating Types of Self-Reported Alcohol Abstinence
Gordon KS, McGinnis K, Dao C, Rentsch CT, Small A, Smith RV, Kember RL, Gelernter J, Kranzler HR, Bryant KJ, Tate JP, Justice AC. Differentiating Types of Self-Reported Alcohol Abstinence. AIDS And Behavior 2019, 24: 655-665. PMID: 31435887, PMCID: PMC6994373, DOI: 10.1007/s10461-019-02638-x.Peer-Reviewed Original ResearchConceptsLifetime abstainersSelf-reported alcohol abstinenceAlcohol biomarkersGenetic polymorphismsLogistic regression modelsHepatitis CAlcohol abstinenceUninfected individualsCharacteristics of peopleAlcohol useAbstinenceHealth effectsSmokingAbstainersBiomarkersRegression modelsOddsAssociationPLWHPolymorphismHIVCocaineApolipoprotein 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 carriersPatterns and Correlates of Prescription Opioid Receipt Among US Veterans: A National, 18-Year Observational Cohort Study
Rentsch CT, Edelman EJ, Justice AC, Marshall BDL, Xu K, Smith AH, Crystal S, Gaither JR, Gordon AJ, Smith RV, Kember RL, Polimanti R, Gelernter J, Fiellin DA, Tate JP, Kranzler HR, Becker WC. Patterns and Correlates of Prescription Opioid Receipt Among US Veterans: A National, 18-Year Observational Cohort Study. AIDS And Behavior 2019, 23: 3340-3349. PMID: 31317364, PMCID: PMC7344341, DOI: 10.1007/s10461-019-02608-3.Peer-Reviewed Original ResearchConceptsOpioid use disorderOpioid receiptCohort studyLong-term opioid therapyVeterans Aging Cohort StudyLatent growth mixture modellingPrescription opioid receiptObservational cohort studyAging Cohort StudyOpioid therapyCause mortalityHepatitis COpioid prescriptionsFuture prevention researchOUD diagnosisGrowth mixture modellingUS veteransHigh prevalenceLow doseHigh incidenceUse disordersPrevention researchGenetic discoveriesReceiptHIVSalivary microRNAs identified by small RNA sequencing and machine learning as potential biomarkers of alcohol dependence
Rosato AJ, Chen X, Tanaka Y, Farrer LA, Kranzler HR, Nunez YZ, Henderson DC, Gelernter J, Zhang H. Salivary microRNAs identified by small RNA sequencing and machine learning as potential biomarkers of alcohol dependence. Epigenomics 2019, 11: 739-749. PMID: 31140863, PMCID: PMC6595542, DOI: 10.2217/epi-2018-0177.Peer-Reviewed Original ResearchMultivariate Analyses Reveal Biological Components Related to Neuronal Signaling and Immunity Mediating Electroencephalograms Abnormalities in Alcohol‐Dependent Individuals from the Collaborative Study on the Genetics of Alcoholism Cohort
Meda SA, Narayanan B, Chorlian D, Meyers JL, Gelernter J, Hesselbrock V, Bauer L, Calhoun VD, Porjesz B, Pearlson G. Multivariate Analyses Reveal Biological Components Related to Neuronal Signaling and Immunity Mediating Electroencephalograms Abnormalities in Alcohol‐Dependent Individuals from the Collaborative Study on the Genetics of Alcoholism Cohort. Alcohol Clinical And Experimental Research 2019, 43: 1462-1477. PMID: 31009096, DOI: 10.1111/acer.14063.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAlcoholismCase-Control StudiesCohort StudiesElectroencephalographyFemaleGenetic Association StudiesGenome-Wide Association StudyGenotypeHumansMaleMiddle AgedMultigene FamilyNeuronsPhenotypePolymorphism, Single NucleotideSignal TransductionSubstance-Related DisordersWhite PeopleYoung AdultConceptsGenetic clustersSingle nucleotide polymorphism dataSignificant genotype-phenotype associationsNucleotide polymorphism dataLipid/cholesterol metabolismLinkage-based analysisGenotype-phenotype relationshipsGenotype-phenotype associationsGene clusterCell signalingPolymorphism dataMolecular mechanismsAlcoholism datasetGenomewide associationTop hitsGenetic componentNeuronal signalingGeneticsSignalingBiological componentsRelationship pairsCholesterol metabolismNeurogenesisSNP componentParallel independent component analysis