2023
Genome-wide association study of antisocial personality disorder diagnostic criteria provides evidence for shared risk factors across disorders
Li W, Zhou H, Thygesen J, Heydtmann M, Smith I, Degenhardt F, Nöthen M, Morgan M, Kranzler H, Gelernter J, Bass N, McQuillin A. Genome-wide association study of antisocial personality disorder diagnostic criteria provides evidence for shared risk factors across disorders. Psychiatric Genetics 2023, 33: 233-242. PMID: 37756443, PMCID: PMC10635348, DOI: 10.1097/ypg.0000000000000352.Peer-Reviewed Original ResearchConceptsAntisocial personality disorderAttention deficit hyperactivity disorderSubstance use disordersPosttraumatic stress disorderGenome-wide association studiesDeficit hyperactivity disorderDisorder diagnostic criteriaRisk factorsFrontal cortexDiagnostic criteriaUse disordersRisk score analysisAnterior cingulateAlcohol-dependent participantsPsychiatric conditionsSignificant associationBrain regionsPersonality disorder diagnostic criteriaStress disorderAnxiety disordersASPD criteriaHyperactivity disorderPolygenic risk score analysisPersonality disorderScore analysisProfiling neuronal methylome and hydroxymethylome of opioid use disorder in the human orbitofrontal cortex
Rompala G, Nagamatsu S, Martínez-Magaña J, Nuñez-Ríos D, Wang J, Girgenti M, Krystal J, Gelernter J, Hurd Y, Montalvo-Ortiz J. Profiling neuronal methylome and hydroxymethylome of opioid use disorder in the human orbitofrontal cortex. Nature Communications 2023, 14: 4544. PMID: 37507366, PMCID: PMC10382503, DOI: 10.1038/s41467-023-40285-y.Peer-Reviewed Original ResearchConceptsOpioid use disorderMulti-omics findingsGene expression patternsCo-methylation analysisGene expression profilesMulti-omics profilingGene networksDNA methylationNeuronal methylomesDNA hydroxymethylationMethylomic analysisExpression patternsExpression profilesEpigenetic disturbancesUse disordersPsychiatric traitsOrbitofrontal cortexOpioid-related drugsPostmortem orbitofrontal cortexEnvironmental factorsDrug interaction analysisOUD treatmentHuman orbitofrontal cortexOpioid signalingInteraction analysisPolysubstance addiction patterns among 7,989 individuals with cocaine use disorder
Stiltner B, Pietrzak R, Tylee D, Nunez Y, Adhikari K, Kranzler H, Gelernter J, Polimanti R. Polysubstance addiction patterns among 7,989 individuals with cocaine use disorder. IScience 2023, 26: 107336. PMID: 37554454, PMCID: PMC10405253, DOI: 10.1016/j.isci.2023.107336.Peer-Reviewed Original ResearchCocaine use disorderUse disordersAddiction patternsMixed bipolar episodesLatent class analysisDSM-5 diagnosisPosttraumatic stress disorderAntisocial personality disorderPsA severityMedication useHigher PSAPSA subgroupsHigher oddsBipolar episodesStress disorderPersonality disorderDisordersSubgroupsAgeSexClass analysisParticipantsComorbiditiesDiseaseDiagnosisDoes polygenic risk for substance‐related traits predict ages of onset and progression of symptoms?
Kranzler H, Feinn R, Xu H, Ho B, Saini D, Nicastro O, Jacoby A, Toikumo S, Gelernter J, Hartwell E, Kember R. Does polygenic risk for substance‐related traits predict ages of onset and progression of symptoms? Addiction 2023, 118: 1675-1686. PMID: 37069489, PMCID: PMC10525011, DOI: 10.1111/add.16210.Peer-Reviewed Original ResearchConceptsOpioid use disorderSubstance use disordersProgression of symptomsPolygenic risk scoresAlcohol use disorderUse disordersAfrican ancestry individualsGenetic riskRegular useEuropean ancestry individualsEarly onsetMore rapid progressionRegular alcohol useShorter progression timeAge of onsetFirst substance useDiscovery sampleUS inpatientsOnset of problemsOutpatient settingDisease progressionRapid progressionSymptom progressionRisk scoreGenome-wide association studiesMultivariate genome-wide association meta-analysis of over 1 million subjects identifies loci underlying multiple substance use disorders
Hatoum A, Colbert S, Johnson E, Huggett S, Deak J, Pathak G, Jennings M, Paul S, Karcher N, Hansen I, Baranger D, Edwards A, Grotzinger A, Tucker-Drob E, Kranzler H, Davis L, Sanchez-Roige S, Polimanti R, Gelernter J, Edenberg H, Bogdan R, Agrawal A. Multivariate genome-wide association meta-analysis of over 1 million subjects identifies loci underlying multiple substance use disorders. Nature Mental Health 2023, 1: 210-223. PMID: 37250466, PMCID: PMC10217792, DOI: 10.1038/s44220-023-00034-y.Peer-Reviewed Original ResearchGenome-wide associationGenetic risk lociIndependent single nucleotide polymorphismsProblematic tobacco useSingle nucleotide polymorphismsRisk lociHigh polygenicityLociReceptor geneAddiction risk factorsPolygenic risk scoresEuropean descentPolygenicityGenesSummary statisticsSubstance use disordersSomatic conditionsAncestryRegulationConfersUse disordersPolymorphismGenetic liabilityDopamine regulationPDE4BTrajectories of alcohol consumption in U.S. military veterans: Results from a 10-year population-based longitudinal study
Na P, Montalvo-Ortiz J, Petrakis I, Krystal J, Polimanti R, Gelernter J, Pietrzak R. Trajectories of alcohol consumption in U.S. military veterans: Results from a 10-year population-based longitudinal study. Drug And Alcohol Dependence 2023, 246: 109833. PMID: 36963160, PMCID: PMC10811960, DOI: 10.1016/j.drugalcdep.2023.109833.Peer-Reviewed Original ResearchConceptsAlcohol consumption groupCurrent mental health treatmentDysphoric arousal symptomsMental health treatmentUS veteransAlcohol consumptionHealth treatmentConsumption groupArousal symptomsYounger agePopulation-based longitudinal studyPublic health problemLongitudinal studyExcessive alcohol consumptionAlcohol use disorderPosttraumatic stress disorderU.S. military veteransMedical comorbiditiesChronic courseNational HealthClose monitoringUse disordersHealth problemsVeterans StudyStress disorder
2022
Cross-ancestry meta-analysis of opioid use disorder uncovers novel loci with predominant effects in brain regions associated with addiction
Kember RL, Vickers-Smith R, Xu H, Toikumo S, Niarchou M, Zhou H, Hartwell EE, Crist RC, Rentsch CT, Davis L, Justice A, Sanchez-Roige S, Kampman K, Gelernter J, Kranzler H. Cross-ancestry meta-analysis of opioid use disorder uncovers novel loci with predominant effects in brain regions associated with addiction. Nature Neuroscience 2022, 25: 1279-1287. PMID: 36171425, PMCID: PMC9682545, DOI: 10.1038/s41593-022-01160-z.Peer-Reviewed Original ResearchConceptsOpioid use disorderGenome-wide association studiesWide significant lociGene expression enrichmentSignificant genetic correlationsCell type groupSignificant lociAssociation studiesExpression enrichmentMillion Veteran ProgramGenetic correlationsUse disordersLociBrain regionsExonic variantsIntronic variantsSubstance use disordersTraitsBiological basisOpioid epidemicPsychiatric disordersVeteran ProgramBrain diseasesTSNARE1FBXW4Psychosocial Factors Associated With Accelerated GrimAge in Male U.S. Military Veterans
Tamman AJF, Nagamatsu S, Krystal JH, Gelernter J, Montalvo-Ortiz JL, Pietrzak RH. Psychosocial Factors Associated With Accelerated GrimAge in Male U.S. Military Veterans. American Journal Of Geriatric Psychiatry 2022, 31: 97-109. PMID: 36210262, DOI: 10.1016/j.jagp.2022.09.002.Peer-Reviewed Original ResearchConceptsRisk factorsPremature mortalityU.S. veteransPsychosocial variablesNovel epigenetic clockLifetime substance use disorderRisk stratification modelMale U.S. veteransCross-sectional studyU.S. veteran populationWeekly physical exerciseSubstance use disordersMale U.S. military veteransBiological agingU.S. military veteransHealth morbidityModifiable correlatesMortality riskSleep qualityHigh riskGreater oddsUse disordersPhysical exercisePsychosocial factorsVeteran populationPhenome-wide Association Analysis of Substance Use Disorders in a Deeply Phenotyped Sample
Kember RL, Hartwell EE, Xu H, Rotenberg J, Almasy L, Zhou H, Gelernter J, Kranzler HR. Phenome-wide Association Analysis of Substance Use Disorders in a Deeply Phenotyped Sample. Biological Psychiatry 2022, 93: 536-545. PMID: 36273948, PMCID: PMC9931661, DOI: 10.1016/j.biopsych.2022.08.010.Peer-Reviewed Original ResearchConceptsSubstance use disordersAlcohol use disorderOpioid use disorderPolygenic risk scoresUse disordersCo-occurring psychiatric disordersComprehensive psychiatric interviewSemi-Structured AssessmentElectronic health recordsControl subjectsLow prevalencePsychiatric interviewRisk scorePsychiatric disordersPhenome-wide association analysisDrug dependenceEuropean individualsHealth recordsLifetime cannabisPhenome-wide association studyDisordersAfrican ancestry individualsDSM diagnosesPopulation sampleGenetic liabilityAssociations 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 functionUnique and joint associations of polygenic risk for major depression and opioid use disorder with endogenous opioid system function
Love T, Shabalin AA, Kember RL, Docherty AR, Zhou H, Koppelmans V, Gelernter J, Baker AK, Hartwell E, Dubroff J, Zubieta JK, Kranzler HR. Unique and joint associations of polygenic risk for major depression and opioid use disorder with endogenous opioid system function. Neuropsychopharmacology 2022, 47: 1784-1790. PMID: 35545664, PMCID: PMC9372136, DOI: 10.1038/s41386-022-01325-1.Peer-Reviewed Original ResearchConceptsOpioid use disorderMajor depressive disorderPolygenic risk scoresUse disordersEndogenous opioid system functionOpioid system functionOpioid system activityMDD polygenic risk scoresPolygenic riskAssociation of PRSEndogenous opioid responseOpioid system activationNon-displaceable bindingPathophysiologic linkOpioid responseMOR availabilityOpioid releaseDepressive disorderMajor depressionNeurotransmitter systemsVentral pallidumRisk scoreReceptor concentrationSystem activationRegion of interestGenome-wide meta-analysis of alcohol use disorder in East Asians
Zhou H, Kalayasiri R, Sun Y, Nuñez YZ, Deng HW, Chen XD, Justice AC, Kranzler HR, Chang S, Lu L, Shi J, Sanichwankul K, Mutirangura A, Malison RT, Gelernter J. Genome-wide meta-analysis of alcohol use disorder in East Asians. Neuropsychopharmacology 2022, 47: 1791-1797. PMID: 35094024, PMCID: PMC9372033, DOI: 10.1038/s41386-022-01265-w.Peer-Reviewed Original ResearchConceptsAlcohol use disorderAlcohol dependenceUse disordersICD-9-CM diagnosisGenome-wide association studiesEast Asian subjectsElectronic health recordsPack yearsLeading causePolygenic risk scoresThai cohortRisk scoreAlcohol consumptionDSM-IVAsian subjectsCohortMillion Veteran Program sampleHealth recordsLarge genome-wide association studiesEast AsiansOngoing recruitmentRisk genesDisordersRisk lociSubjectsPost‐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
2021
Investigation of convergent and divergent genetic influences underlying schizophrenia and alcohol use disorder
Johnson EC, Kapoor M, Hatoum AS, Zhou H, Polimanti R, Wendt FR, Walters RK, Lai D, Kember RL, Hartz S, Meyers JL, Peterson RE, Ripke S, Bigdeli TB, Fanous AH, Pato CN, Pato MT, Goate AM, Kranzler HR, O'Donovan MC, Walters JTR, Gelernter J, Edenberg HJ, Agrawal A. Investigation of convergent and divergent genetic influences underlying schizophrenia and alcohol use disorder. Psychological Medicine 2021, 53: 1196-1204. PMID: 34231451, PMCID: PMC8738774, DOI: 10.1017/s003329172100266x.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesGenome-wide significant single nucleotide polymorphismsLarge-scale genome-wide association studiesSignificant single nucleotide polymorphismsIndependent genome-wide significant single nucleotide polymorphismsSignificant genetic correlationsGenomic regionsSingle nucleotide polymorphismsGene expressionGenetic covariancePleiotropic associationsAssociation studiesGenetic correlationsGenetic variantsNucleotide polymorphismsGenetic overlapDisorder-specific effectsAlcohol use disorderGenetic influencesGenesUse disordersGenome-wide association study of stimulant dependence
Cox J, Sherva R, Wetherill L, Foroud T, Edenberg HJ, Kranzler HR, Gelernter J, Farrer LA. Genome-wide association study of stimulant dependence. Translational Psychiatry 2021, 11: 363. PMID: 34226506, PMCID: PMC8257618, DOI: 10.1038/s41398-021-01440-5.Peer-Reviewed Original ResearchConceptsStimulant dependenceAssociation studiesVoltage-gated channel proteinsGenome-wide association studiesNicotinic acetylcholine receptor genesTop GWAS signalsUse disordersAcetylcholine receptor genesWide association studyGWAS signalsSubstance use disordersEuropean ancestry subjectsNovel genesCocaine use disorderUsers of cocaineChannel proteinsGenetic studiesSpecific genetic factorsGenetics of AlcoholismSignificant pleiotropy
2020
Association 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 Revision
2019
FUNCTIONAL CODING VARIANT IN OPRM1 GENE ASSOCIATED WITH OPIOID USE DISORDER: EVIDENCE FROM GWAS ON LARGE COHORTS
Zhou H, Rentsch C, Cheng Z, Kember R, Nunex Y, Tate J, Dao C, Polimanti R, Justice A, Kranzler H, Gelernter J. FUNCTIONAL CODING VARIANT IN OPRM1 GENE ASSOCIATED WITH OPIOID USE DISORDER: EVIDENCE FROM GWAS ON LARGE COHORTS. European Neuropsychopharmacology 2019, 29: s34-s35. DOI: 10.1016/j.euroneuro.2019.07.070.Peer-Reviewed Original ResearchPatterns 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 discoveriesReceiptHIV
2017
Trauma exposure interacts with the genetic risk of bipolar disorder in alcohol misuse of US soldiers
Polimanti R, Kaufman J, Zhao H, Kranzler HR, Ursano RJ, Kessler RC, Stein MB, Gelernter J. Trauma exposure interacts with the genetic risk of bipolar disorder in alcohol misuse of US soldiers. Acta Psychiatrica Scandinavica 2017, 137: 148-156. PMID: 29230810, PMCID: PMC6110087, DOI: 10.1111/acps.12843.Peer-Reviewed Original ResearchConceptsBD polygenic risk scorePolygenic risk scoresAlcohol misuseBipolar disorderTrauma exposurePsychiatric disordersGenetic riskMajor depressive disorderNicotine dependence symptomsSubstance use disordersSchizophrenia polygenic risk scoresVoltage-gated calcium channel activityCalcium channel activityUS Army soldiersBeta2-adrenergic receptorDepressive disorderRisk scoreUse disordersAdrenergic receptorsMental disordersSubstance abuseDisordersDependence symptomsChannel activityExposureSchizophrenia and substance use comorbidity: a genome-wide perspective
Polimanti R, Agrawal A, Gelernter J. Schizophrenia and substance use comorbidity: a genome-wide perspective. Genome Medicine 2017, 9: 25. PMID: 28327175, PMCID: PMC5359801, DOI: 10.1186/s13073-017-0423-3.Peer-Reviewed Original ResearchConceptsSubstance use disordersPublic health messagesPremature mortalityPsychiatric disordersUse disordersDual diagnosisHealth messagesRecent genetic investigationsDiagnosisSchizophreniaDisordersGenetic investigationsWide association studyAssociation studiesComorbiditiesMortalityGenome-wide perspective