Featured Publications
Genome-wide association studies and cross-population meta-analyses investigating short and long sleep duration
Austin-Zimmerman I, Levey D, Giannakopoulou O, Deak J, Galimberti M, Adhikari K, Zhou H, Denaxas S, Irizar H, Kuchenbaecker K, McQuillin A, Concato J, Buysse D, Gaziano J, Gottlieb D, Polimanti R, Stein M, Bramon E, Gelernter J. Genome-wide association studies and cross-population meta-analyses investigating short and long sleep duration. Nature Communications 2023, 14: 6059. PMID: 37770476, PMCID: PMC10539313, DOI: 10.1038/s41467-023-41249-y.Peer-Reviewed Original ResearchConceptsAssociation studiesGenome-wide association studiesGenetic correlationsWide association studyLinkage disequilibrium scorePositive genetic correlationSleep traitsIndependent lociMillion Veteran ProgramTraitsAncestryUK BiobankVeteran ProgramMendelian randomisationLociHeritabilitySNPsPhenotypeEast AsiansSimilar patternCardiometabolic phenotypesGenome-wide association study of post-traumatic stress disorder reexperiencing symptoms in >165,000 US veterans
Gelernter J, Sun N, Polimanti R, Pietrzak R, Levey DF, Bryois J, Lu Q, Hu Y, Li B, Radhakrishnan K, Aslan M, Cheung KH, Li Y, Rajeevan N, Sayward F, Harrington K, Chen Q, Cho K, Pyarajan S, Sullivan PF, Quaden R, Shi Y, Hunter-Zinck H, Gaziano JM, Concato J, Zhao H, Stein MB. Genome-wide association study of post-traumatic stress disorder reexperiencing symptoms in >165,000 US veterans. Nature Neuroscience 2019, 22: 1394-1401. PMID: 31358989, PMCID: PMC6953633, DOI: 10.1038/s41593-019-0447-7.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesAssociation studiesHigh linkage disequilibrium regionLinkage disequilibrium regionWide association studyDisequilibrium regionBioinformatics analysisTranscriptomic profilesMillion Veteran ProgramChromosome 17Genetic risk factorsNew insightsUK Biobank dataReexperiencing of traumaStriatal medium spiny neuronsVeteran ProgramSignificant regionsCAMKVEuropean AmericansBiobank dataMedium spiny neuronsTCF4BiologyKANSL1African American cohortGenome-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
Genome-wide meta-analysis of myasthenia gravis uncovers new loci and provides insights into polygenic prediction
Braun A, Shekhar S, Levey D, Straub P, Kraft J, Panagiotaropoulou G, Heilbron K, Awasthi S, Meleka Hanna R, Hoffmann S, Stein M, Lehnerer S, Mergenthaler P, Elnahas A, Topaloudi A, Koromina M, Palviainen T, Asbjornsdottir B, Stefansson H, Skuladóttir A, Jónsdóttir I, Stefansson K, Reis K, Esko T, Palotie A, Leypoldt F, Stein M, Fontanillas P, Kaprio J, Gelernter J, Davis L, Paschou P, Tannemaat M, Verschuuren J, Kuhlenbäumer G, Gregersen P, Huijbers M, Stascheit F, Meisel A, Ripke S. Genome-wide meta-analysis of myasthenia gravis uncovers new loci and provides insights into polygenic prediction. Nature Communications 2024, 15: 9839. PMID: 39537604, PMCID: PMC11560923, DOI: 10.1038/s41467-024-53595-6.Peer-Reviewed Original ResearchConceptsPerformance of polygenic risk scoresGenome-wide significant hitsGenome-wide association studiesGenome-wide meta-analysisControls of European ancestryGenetic architecturePolygenic risk scoresSignificant hitsAssociation studiesPhenotypic variationPolygenic predictionEuropean ancestryAssociated with early-onsetHuman leukocyte antigen allelesLociEarly-onsetReplication studyNeuromuscular junctionMyasthenia gravisAutoantibody-mediated diseasesAntigen allelesAllelesAncestryDisease manifestationsLate-onset MGAssociation 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 patternsAssociation
2023
Polygenic risk score for problematic alcohol use predicts heavy drinking and alcohol use disorder symptoms in young adulthood after accounting for adolescent alcohol use and parental alcohol use disorder
Wang F, Hicks B, Zhou H, Kranzler H, Gelernter J, Zucker R. Polygenic risk score for problematic alcohol use predicts heavy drinking and alcohol use disorder symptoms in young adulthood after accounting for adolescent alcohol use and parental alcohol use disorder. Drug And Alcohol Dependence 2023, 248: 109909. PMID: 37163864, PMCID: PMC11013565, DOI: 10.1016/j.drugalcdep.2023.109909.Peer-Reviewed Original Research
2022
Alcohol withdrawal in past‐year drinkers with unhealthy alcohol use: Prevalence, characteristics, and correlates in a national epidemiologic survey
Livne O, Feinn R, Knox J, Hartwell EE, Gelernter J, Hasin DS, Kranzler HR. Alcohol withdrawal in past‐year drinkers with unhealthy alcohol use: Prevalence, characteristics, and correlates in a national epidemiologic survey. Alcohol Clinical And Experimental Research 2022, 46: 422-433. PMID: 35275407, PMCID: PMC8928097, DOI: 10.1111/acer.14781.Peer-Reviewed Original ResearchConceptsAlcohol withdrawal syndromeUnhealthy alcohol useSerious adverse outcomesNational Epidemiologic SurveyAlcohol useHealthcare utilizationAdverse outcomesGeneral populationPsychiatric disordersEpidemiologic SurveyAlcohol Use Disorders Identification Test-Consumption (AUDIT-C) questionnairePast-year alcohol use disorderNausea/vomitingMajor depressive disorderImportant clinical populationAlcohol use disorderRelated Conditions-IIIBorderline personality disorderPast-year prevalenceAlcohol withdrawalWithdrawal syndromeWithdrawal symptomsDepressive disorderUnhealthy drinkersHigher odds
2021
Drinking and smoking polygenic risk is associated with childhood and early-adulthood psychiatric and behavioral traits independently of substance use and psychiatric genetic risk
De Angelis F, Wendt FR, Pathak GA, Tylee DS, Goswami A, Gelernter J, Polimanti R. Drinking and smoking polygenic risk is associated with childhood and early-adulthood psychiatric and behavioral traits independently of substance use and psychiatric genetic risk. Translational Psychiatry 2021, 11: 586. PMID: 34775470, PMCID: PMC8590689, DOI: 10.1038/s41398-021-01713-z.Peer-Reviewed Original ResearchConceptsSubstance useYoung adultsBehavioral traitsPhiladelphia Neurodevelopmental CohortRemoval of participantsAnxiety-related traitsRisk-taking behaviorVerbal reasoningCognitive performancePolygenic risk scoresSocial competenciesNeurobiological processesNeurodevelopmental CohortPsychiatric genetic riskDrinking behaviorParent educationPRS associationsPolygenic riskPsychopathologyGenetic overlapPsychotic symptomsAdverse health outcomesHazardous behaviorEducational attainmentTobacco smoking
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 tissueDivergencePolygenic risk for autism spectrum disorder associates with anger recognition in a neurodevelopment-focused phenome-wide scan of unaffected youths from a population-based cohort
Wendt FR, Carvalho CM, Pathak GA, Gelernter J, Polimanti R. Polygenic risk for autism spectrum disorder associates with anger recognition in a neurodevelopment-focused phenome-wide scan of unaffected youths from a population-based cohort. PLOS Genetics 2020, 16: e1009036. PMID: 32941431, PMCID: PMC7523983, DOI: 10.1371/journal.pgen.1009036.Peer-Reviewed Original ResearchA 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 AdultDifferentiating 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 modelsOddsAssociationPLWHPolymorphismHIVCocainePatterns 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 analysisGenome‐wide analyses of psychological resilience in U.S. Army soldiers
Stein MB, Choi KW, Jain S, Campbell‐Sills L, Chen C, Gelernter J, He F, Heeringa SG, Maihofer AX, Nievergelt C, Nock MK, Ripke S, Sun X, Kessler RC, Smoller JW, Ursano RJ. Genome‐wide analyses of psychological resilience in U.S. Army soldiers. American Journal Of Medical Genetics Part B Neuropsychiatric Genetics 2019, 180: 310-319. PMID: 31081985, PMCID: PMC6551278, DOI: 10.1002/ajmg.b.32730.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesGenome-wide significant lociGenome-wide significant associationGenome-wide analysisCommon variant heritabilityGenome-wide significanceIntergenic regionSecond geneSignificant lociGenetic basisMolecular basisKinase 2Association studiesMember 5Genetic determinantsDoublecortin familyLociBiological basisPolygenic risk scoresNew avenuesGenome-wide Association Study of Maximum Habitual Alcohol Intake in >140,000 U.S. European and African American Veterans Yields Novel Risk Loci
Gelernter J, Sun N, Polimanti R, Pietrzak RH, Levey DF, Lu Q, Hu Y, Li B, Radhakrishnan K, Aslan M, Cheung KH, Li Y, Rajeevan N, Sayward F, Harrington K, Chen Q, Cho K, Honerlaw J, Pyarajan S, Lencz T, Quaden R, Shi Y, Hunter-Zinck H, Gaziano JM, Kranzler HR, Concato J, Zhao H, Stein MB, Program D, Program M. Genome-wide Association Study of Maximum Habitual Alcohol Intake in >140,000 U.S. European and African American Veterans Yields Novel Risk Loci. Biological Psychiatry 2019, 86: 365-376. PMID: 31151762, PMCID: PMC6919570, DOI: 10.1016/j.biopsych.2019.03.984.Peer-Reviewed Original ResearchConceptsAdditional genome-wide significant lociRisk lociWide association study (GWAS) analysisAssociation studiesGenome-wide significant lociGenome-wide association studiesGenetic correlationsWide association studyNovel risk lociAlcohol-related traitsStrong statistical supportSmoking-related traitsAdditional genomesSignificant lociPancreatic delta cellsChromosome 4Chromosome 11Protein productsChromosome 8Quantitative phenotypesMillion Veteran ProgramVeterans Affairs Million Veteran ProgramLociCell typesChromosome 17Evidence of causal effect of major depression on alcohol dependence: findings from the psychiatric genomics consortium
Polimanti R, Peterson RE, Ong JS, MacGregor S, Edwards AC, Clarke TK, Frank J, Gerring Z, Gillespie NA, Lind PA, Maes HH, Martin NG, Mbarek H, Medland SE, Streit F, Agrawal A, Edenberg H, Kendler K, Lewis C, Sullivan P, Wray N, Gelernter J, Derks E. Evidence of causal effect of major depression on alcohol dependence: findings from the psychiatric genomics consortium. Psychological Medicine 2019, 49: 1218-1226. PMID: 30929657, PMCID: PMC6565601, DOI: 10.1017/s0033291719000667.Peer-Reviewed Original ResearchConceptsMajor depressionAlcohol dependenceAlcohol consumptionPsychiatric Genomics ConsortiumImportant public health concernMendelian randomizationPublic health concernUK BiobankClinical associationsHealth concernMR analysisReverse causationCausal roleNon-significant resultsCausal relationshipGenetic liabilityGenomics ConsortiumLinkage disequilibrium score regressionIntervention efforts