2024
Genetic and non-genetic predictors of risk for opioid dependence.
Na P, Deak J, Kranzler H, Pietrzak R, Gelernter J. Genetic and non-genetic predictors of risk for opioid dependence. Psychological Medicine 2024, 54: 1779-1786. PMID: 38317430, PMCID: PMC11132928, DOI: 10.1017/s0033291723003732.Peer-Reviewed Original ResearchPolygenic risk scoresMulti-trait analysis of genome-wide association studyOpioid use disorderPosttraumatic stress disorderPsychosocial/environmental factorsAnalysis of genome-wide association studiesHigher education levelGenome-wide association studiesNon-genetic predictorsEuropean-ancestry adultsEtiology of ODPublic health crisisPsychosocial factorsPolygenic riskMulti-trait analysisEducation levelPsychosocial environmentHousehold incomeRisk scoreAssociation studiesOpioid dependenceDiagnosis of ODLifetime diagnosisYale-PennAssociated with OD
2021
Multi-environment gene interactions linked to the interplay between polysubstance dependence and suicidality
Polimanti R, Levey DF, Pathak GA, Wendt FR, Nunez YZ, Ursano RJ, Kessler RC, Kranzler HR, Stein MB, Gelernter J. Multi-environment gene interactions linked to the interplay between polysubstance dependence and suicidality. Translational Psychiatry 2021, 11: 34. PMID: 33431810, PMCID: PMC7801457, DOI: 10.1038/s41398-020-01153-1.Peer-Reviewed Original ResearchConceptsSuicidal ideationPolysubstance dependenceSuicide attemptsOdds ratioGene-environment interactionsYale-PennMultivariate logistic regressionImportant risk factorMultivariate gene-environment interactionsMental health risksOpioid dependenceRisk factorsNicotine dependenceSuicidality outcomesCocaine dependenceLogistic regressionSubstance dependenceSuicidalityCohortLifetime suicidalityLinear mixed modelsMultiple substancesArmy STARRSArmy personnelHealth risks
2020
Leveraging genome-wide data to investigate differences between opioid use vs. opioid dependence in 41,176 individuals from the Psychiatric Genomics Consortium
Polimanti R, Walters RK, Johnson EC, McClintick JN, Adkins AE, Adkins DE, Bacanu SA, Bierut LJ, Bigdeli TB, Brown S, Bucholz KK, Copeland WE, Costello EJ, Degenhardt L, Farrer LA, Foroud TM, Fox L, Goate AM, Grucza R, Hack LM, Hancock DB, Hartz SM, Heath AC, Hewitt JK, Hopfer CJ, Johnson EO, Kendler KS, Kranzler HR, Krauter K, Lai D, Madden PAF, Martin NG, Maes HH, Nelson EC, Peterson RE, Porjesz B, Riley BP, Saccone N, Stallings M, Wall TL, Webb BT, Wetherill L, Edenberg H, Agrawal A, Gelernter J. Leveraging genome-wide data to investigate differences between opioid use vs. opioid dependence in 41,176 individuals from the Psychiatric Genomics Consortium. Molecular Psychiatry 2020, 25: 1673-1687. PMID: 32099098, PMCID: PMC7392789, DOI: 10.1038/s41380-020-0677-9.Peer-Reviewed Original Research
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 studyPutamenLungGenomewide Study of Epigenetic Biomarkers of Opioid Dependence in European- American Women
Montalvo-Ortiz JL, Cheng Z, Kranzler HR, Zhang H, Gelernter J. Genomewide Study of Epigenetic Biomarkers of Opioid Dependence in European- American Women. Scientific Reports 2019, 9: 4660. PMID: 30874594, PMCID: PMC6420601, DOI: 10.1038/s41598-019-41110-7.Peer-Reviewed Original ResearchConceptsEpigenome-wide association studiesEpigenetic mechanismsAssociation studiesAssociation analysisCpG sitesFirst epigenome-wide association studyGenome-wide association studiesPrevious genome-wide association studyCandidate gene approachChromatin remodelingDNA bindingGene approachGenomewide studiesDNA methylation ageCell survivalEpigenetic biomarkersRisk variantsPopulation stratificationMethylation ageGenesCell projectionsOpioid dependenceNovel peripheral biomarkersEuropean American womenCell proportion
2018
Genome-wide Association Study Identifies a Regulatory Variant of RGMA Associated With Opioid Dependence in European Americans
Cheng Z, Zhou H, Sherva R, Farrer LA, Kranzler HR, Gelernter J. Genome-wide Association Study Identifies a Regulatory Variant of RGMA Associated With Opioid Dependence in European Americans. Biological Psychiatry 2018, 84: 762-770. PMID: 29478698, PMCID: PMC6041180, DOI: 10.1016/j.biopsych.2017.12.016.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesAssociation studiesHomologous mouse geneMouse geneAxon guidance proteinRegulatory variantsCoexpression analysisOpioid dependenceTranscript variantsGenetic studiesChromosome 15Guidance proteinsRNA expressionNominal significanceMessenger RNA expressionGenesRepulsive guidance molecule AHigh expressionRGMaRisk allelesChronic morphine injectionDSM-IV diagnosisExpressionNew leadsMorphine injection
2017
Genome-wide association study of therapeutic opioid dosing identifies a novel locus upstream of OPRM1
Smith AH, Jensen KP, Li J, Nunez Y, Farrer LA, Hakonarson H, Cook-Sather SD, Kranzler HR, Gelernter J. Genome-wide association study of therapeutic opioid dosing identifies a novel locus upstream of OPRM1. Molecular Psychiatry 2017, 22: 346-352. PMID: 28115739, PMCID: PMC5407902, DOI: 10.1038/mp.2016.257.Peer-Reviewed Original ResearchMeSH KeywordsAdultAllelesAnalgesics, OpioidBlack or African AmericanDose-Response Relationship, DrugFemaleGene FrequencyGenetic Predisposition to DiseaseGenome-Wide Association StudyGenotypeHumansMaleMethadoneMiddle AgedMorphineOpioid-Related DisordersPainPolymorphism, Single NucleotideReceptors, Opioid, muUnited StatesWhite PeopleConceptsMethadone doseOD subjectsOpioid dependenceSignificant associationDaily methadone doseMethadone maintenance doseOpioid analgesic doseDose of morphineHigher methadone doseDifferent clinical settingsΜ-opioid receptorAnalgesic doseMaintenance doseOral methadoneEffective analgesicSurgical painOpioid sensitivityPrecision pharmacotherapySelective agonistGenome-wide association studiesAA childrenClinical settingDoseMinor alleleOPRM1
2015
Evidence of CNIH3 involvement in opioid dependence
Nelson EC, Agrawal A, Heath AC, Bogdan R, Sherva R, Zhang B, Al-Hasani R, Bruchas MR, Chou YL, Demers CH, Carey CE, Conley ED, Fakira AK, Farrer LA, Goate A, Gordon S, Henders AK, Hesselbrock V, Kapoor M, Lynskey MT, Madden PA, Moron JA, Rice JP, Saccone NL, Schwab SG, Shand FL, Todorov AA, Wallace L, Wang T, Wray NR, Zhou X, Degenhardt L, Martin NG, Hariri AR, Kranzler HR, Gelernter J, Bierut LJ, Clark DJ, Montgomery GW. Evidence of CNIH3 involvement in opioid dependence. Molecular Psychiatry 2015, 21: 608-614. PMID: 26239289, PMCID: PMC4740268, DOI: 10.1038/mp.2015.102.Peer-Reviewed Original ResearchConceptsSingle nucleotide polymorphismsGenome-wide association studiesComputational genetic analysisEpigenetic annotationsGenetic analysisAssociation studiesGenetic studiesStudy of AddictionVivo functionalityMouse strainsOpioid dependenceNeurogenetics StudySevere addictive disordersΑ-aminoGenesOpioid misusersGeneticsCnih3SNPsDuke Neurogenetics StudyHaplotypesPhenotypeA alleleAllelesFetal brain
2013
Rate of progression from first use to dependence on cocaine or opioids: A cross-substance examination of associated demographic, psychiatric, and childhood risk factors
Sartor CE, Kranzler HR, Gelernter J. Rate of progression from first use to dependence on cocaine or opioids: A cross-substance examination of associated demographic, psychiatric, and childhood risk factors. Addictive Behaviors 2013, 39: 473-479. PMID: 24238782, PMCID: PMC3855905, DOI: 10.1016/j.addbeh.2013.10.021.Peer-Reviewed Original ResearchMeSH KeywordsAdultAge of OnsetAgedAlcohol-Related DisordersBehavior, AddictiveCase-Control StudiesChildChild AbuseCluster AnalysisCocaine-Related DisordersConnecticutCross-Sectional StudiesDiagnosis, Dual (Psychiatry)Disease ProgressionFemaleHumansInterviews as TopicLogistic ModelsMaleMental DisordersMiddle AgedOpioid-Related DisordersPennsylvaniaRisk FactorsSocial EnvironmentSocioeconomic FactorsSouth CarolinaTime FactorsConceptsChildhood risk factorsOpioid dependenceOpioid-dependent participantsRisk factorsCocaine dependenceDependent participantsImportant public health goalRate of progressionPublic health goalsLogistic regression modelsBlack/African AmericanChildhood physical abuseOrdinal logistic regression modelsCocaine-dependent participantsMean ageSlow progressionElevated riskAssociated demographicPsychiatric disordersMulti-site studyDependence diagnosisGreater riskHealth goalsSubstance dependenceConduct disorderDeep resequencing of 17 glutamate system genes identifies rare variants in DISC1 and GRIN2B affecting risk of opioid dependence
Xie P, Kranzler HR, Krystal JH, Farrer LA, Zhao H, Gelernter J. Deep resequencing of 17 glutamate system genes identifies rare variants in DISC1 and GRIN2B affecting risk of opioid dependence. Addiction Biology 2013, 19: 955-964. PMID: 23855403, PMCID: PMC3815683, DOI: 10.1111/adb.12072.Peer-Reviewed Original ResearchConceptsOpioid dependenceSubstance dependenceRare variantsN-methyl-D-aspartate (NMDA) glutamate receptorsCo-occurring alcohol dependenceHealthy control subjectsControl subjectsNMDA systemOpioid abuseGlutamate receptorsSchizophrenia risk genesSD riskAlcohol dependenceSignificant associationCocaine dependenceAdditional subjectsOD riskRisk genesDISC1African AmericansFirst demonstrationCommon variantsRiskSubjectsMinor allele frequency
2011
Empirically derived subtypes of opioid use and related behaviors
Chan G, Gelernter J, Oslin D, Farrer L, Kranzler HR. Empirically derived subtypes of opioid use and related behaviors. Addiction 2011, 106: 1146-1154. PMID: 21306596, PMCID: PMC3164489, DOI: 10.1111/j.1360-0443.2011.03390.x.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAge of OnsetAgedAnalgesics, OpioidChildCluster AnalysisComorbidityDiagnostic and Statistical Manual of Mental DisordersFamily HealthFemaleGenetic Association StudiesGenetic Predisposition to DiseaseGenotypeHumansInterview, PsychologicalMaleMental DisordersMiddle AgedOpioid-Related DisordersPhenotypePrevalenceSiblingsSubstance Abuse, IntravenousUnited StatesYoung AdultConceptsOpioid usePsychiatric disordersHomogeneous subtypesRelated behaviorsSemi-Structured AssessmentGeneral community sampleOpioid dependenceMedical historyPrevalence ratesCocaine dependenceDrug dependenceSubtypesParticipant demographicsSubstance useCase-control genetic studyDemographicsDisordersCommunity sampleGenetic studiesAgitated depression in substance dependence
Leventhal AM, Gelernter J, Oslin D, Anton RF, Farrer LA, Kranzler HR. Agitated depression in substance dependence. Drug And Alcohol Dependence 2011, 116: 163-169. PMID: 21277711, PMCID: PMC3105217, DOI: 10.1016/j.drugalcdep.2010.12.012.Peer-Reviewed Original ResearchConceptsSubstance dependenceOpioid dependenceDSM-IV mental disordersMajor depressive episodeNon-opioid formsLifetime substance dependenceDepression associatesMDE subtypesSedative dependencePsychomotor agitationDepressive episodeDepression subtypesLifetime depressionOpioidsDrug dependenceMental disordersSubtypesCocaineDrugsDepressionPsychiatric phenotypesStructured interviewsPMAAssociationComorbiditiesInter-rater reliability and concurrent validity of DSM-IV opioid dependence in a Hmong isolate using the Thai version of the Semi-Structured Assessment for Drug Dependence and Alcoholism (SSADDA)
Malison RT, Kalayasiri R, Sanichwankul K, Sughondhabirom A, Mutirangura A, Pittman B, Gueorguieva R, Kranzler HR, Gelernter J. Inter-rater reliability and concurrent validity of DSM-IV opioid dependence in a Hmong isolate using the Thai version of the Semi-Structured Assessment for Drug Dependence and Alcoholism (SSADDA). Addictive Behaviors 2011, 36: 156-160. PMID: 20888699, PMCID: PMC2981662, DOI: 10.1016/j.addbeh.2010.08.031.Peer-Reviewed Original Research
2010
Functional impact of a single-nucleotide polymorphism in the OPRD1 promoter region
Zhang H, Gelernter J, Gruen JR, Kranzler HR, Herman AI, Simen AA. Functional impact of a single-nucleotide polymorphism in the OPRD1 promoter region. Journal Of Human Genetics 2010, 55: 278-284. PMID: 20300121, PMCID: PMC2876206, DOI: 10.1038/jhg.2010.22.Peer-Reviewed Original ResearchMeSH KeywordsAllelesCell LineElectrophoretic Mobility Shift AssayGene Expression RegulationHumansLuciferasesNuclear ProteinsOligonucleotide ProbesPolymorphism, Single NucleotidePromoter Regions, GeneticProtein BindingReceptors, Opioid, deltaRecombinant Fusion ProteinsTranscription FactorsTransfectionConceptsMinor G alleleG alleleΔ-opioid receptorsSubstances of abuseDual-luciferase reporterOpioid dependenceBrain nuclear proteinsGreater expression levelsA alleleLuciferase reporterRenilla luciferase vectorsSingle nucleotide polymorphismsLuciferase reporter vectorExpression levelsPromoter regionHEK293 cellsLuciferase vectorFunctional impactLuciferase expressionFunctional significanceExpressionRenilla luciferase expressionReporter vectorTranscription factors
2009
Adverse childhood events as risk factors for substance dependence: Partial mediation by mood and anxiety disorders
Douglas KR, Chan G, Gelernter J, Arias AJ, Anton RF, Weiss RD, Brady K, Poling J, Farrer L, Kranzler HR. Adverse childhood events as risk factors for substance dependence: Partial mediation by mood and anxiety disorders. Addictive Behaviors 2009, 35: 7-13. PMID: 19720467, PMCID: PMC2763992, DOI: 10.1016/j.addbeh.2009.07.004.Peer-Reviewed Original ResearchConceptsAdverse childhood eventsSD riskSubstance dependenceAnxiety disordersRisk factorsNegative health outcomesSemi-Structured AssessmentChildhood eventsOpioid dependenceSD diagnosisLifetime moodEffective treatmentLifetime diagnosisFirst onsetHealth outcomesDrug dependenceEarly life experiencesDisordersChildhood abuseRiskMoodDiagnosisAlcoholismCocaineSources of unreliability in the diagnosis of substance dependence.
Feinn R, Gelernter J, Cubells JF, Farrer L, Kranzler HR. Sources of unreliability in the diagnosis of substance dependence. Journal Of Studies On Alcohol And Drugs 2009, 70: 475-81. PMID: 19371499, PMCID: PMC2670752, DOI: 10.15288/jsad.2009.70.475.Peer-Reviewed Original ResearchConceptsSubstance dependence diagnosesDrug dependenceCommon diagnosisCriterion countsSemi-Structured AssessmentOpioid dependencePsychiatric disordersMost diagnosesOccasion variabilityMental disordersSubstance dependenceDiagnosisStatistical ManualMarijuana dependenceReliable diagnosisFourth EditionDependence categoriesSubjects' reportsSubjectsExcellent reliabilityDisordersCountIndex of dependabilityReportInterviewersPro-Opiomelanocortin Gene Variation Related to Alcohol or Drug Dependence: Evidence and Replications Across Family- and Population-based Studies
Zhang H, Kranzler HR, Weiss RD, Luo X, Brady KT, Anton RF, Farrer LA, Gelernter J. Pro-Opiomelanocortin Gene Variation Related to Alcohol or Drug Dependence: Evidence and Replications Across Family- and Population-based Studies. Biological Psychiatry 2009, 66: 128-136. PMID: 19217079, PMCID: PMC2896237, DOI: 10.1016/j.biopsych.2008.12.021.Peer-Reviewed Original ResearchConceptsOpioid dependencePro-opiomelanocortin geneCocaine dependenceOpioidergic neurotransmissionSubstance dependence
2008
Correlates of co-occurring ADHD in drug-dependent subjects: Prevalence and features of substance dependence and psychiatric disorders
Arias AJ, Gelernter J, Chan G, Weiss RD, Brady KT, Farrer L, Kranzler HR. Correlates of co-occurring ADHD in drug-dependent subjects: Prevalence and features of substance dependence and psychiatric disorders. Addictive Behaviors 2008, 33: 1199-1207. PMID: 18558465, PMCID: PMC2532519, DOI: 10.1016/j.addbeh.2008.05.003.Peer-Reviewed Original ResearchConceptsAttention deficit hyperactivity disorderFirst substance useOpioid dependenceLifetime diagnosisSubstance useCo-occurring attention-deficit hyperactivity disorderSubstance dependence disordersDrug-dependent subjectsSemi-Structured AssessmentDeficit hyperactivity disorderClinical courseMore hospitalizationsSevere coursePsychiatric comorbiditySD diagnosisDependence disordersPsychiatric disordersADHD prevalencePsychiatric diagnosisDrug dependenceMore SDsSubstance dependenceConduct disorderDiagnosisHyperactivity disorder
2007
Reliability of DSM-IV diagnostic criteria using the semi-structured assessment for drug dependence and alcoholism (SSADDA)
Pierucci-Lagha A, Gelernter J, Chan G, Arias A, Cubells JF, Farrer L, Kranzler HR. Reliability of DSM-IV diagnostic criteria using the semi-structured assessment for drug dependence and alcoholism (SSADDA). Drug And Alcohol Dependence 2007, 91: 85-90. PMID: 17590536, PMCID: PMC2039919, DOI: 10.1016/j.drugalcdep.2007.04.014.Peer-Reviewed Original ResearchConceptsDSM-IV diagnosisDSM-IV criteriaSemi-Structured AssessmentDrug dependenceIndividual DSM-IV criteriaDiagnostic reliabilityDiagnostic criteriaSubstance dependenceDSM-IV diagnostic criteriaIndividual diagnostic criteriaSubstance dependence diagnosesOpioid dependenceTest-retest reliabilityInter-rater reliabilityPsychiatric disordersDependence diagnosisCocaine dependenceConfidence intervalsDiagnosisInter-rater reliability estimatesAlcoholismSedativesCriteriaIndividual criteriaSpecific groups
2004
Allelic and haplotypic association of GABRA2 with alcohol dependence
Covault J, Gelernter J, Hesselbrock V, Nellissery M, Kranzler HR. Allelic and haplotypic association of GABRA2 with alcohol dependence. American Journal Of Medical Genetics Part B Neuropsychiatric Genetics 2004, 129B: 104-109. PMID: 15274050, DOI: 10.1002/ajmg.b.30091.Peer-Reviewed Original ResearchConceptsAlcohol-dependent subjectsAlcohol dependenceSingle nucleotide polymorphismsMajor depressive episodeGABAA receptor subunitsSubstance use disordersHaplotypic associationsEvidence of associationSerious morbidityOpioid dependenceAlpha 2 subunitDepressive episodePrevalent disorderUse disordersEuropean-American subjectsNeurotransmitter receptorsControl groupDrug dependenceReceptor subunitsCommon haplotypeGABRA2 geneBehavioral effectsImportant mediatorAssociationSubjects