2024
Gene × environment effects and mediation involving adverse childhood events, mood and anxiety disorders, and substance dependence
Kranzler H, Davis C, Feinn R, Jinwala Z, Khan Y, Oikonomou A, Silva-Lopez D, Burton I, Dixon M, Milone J, Ramirez S, Shifman N, Levey D, Gelernter J, Hartwell E, Kember R. Gene × environment effects and mediation involving adverse childhood events, mood and anxiety disorders, and substance dependence. Nature Human Behaviour 2024, 8: 1616-1627. PMID: 38834750, DOI: 10.1038/s41562-024-01885-w.Peer-Reviewed Original ResearchAdverse childhood eventsSubstance dependenceMood/anxiety disordersAnxiety disordersChildhood eventsIndirect associationsGenetic riskExposure to adverse childhood eventsDevelopment of moodSubstance use disordersAssociations of adverse childhood eventsUse disorderMediation modelMood/anxietyDisorder factorsPolygenic scoresIndirect pathsDisordersEuropean ancestry individualsMoodTreatment approachesAnxietySelf-medicationEuropean ancestryLatent variables
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
2017
Polygenic 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 ResearchConceptsMDD 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 disorder
2015
Association of the OPRM1 Variant rs1799971 (A118G) with Non-Specific Liability to Substance Dependence in a Collaborative de novo Meta-Analysis of European-Ancestry Cohorts
Schwantes-An TH, Zhang J, Chen LS, Hartz SM, Culverhouse RC, Chen X, Coon H, Frank J, Kamens HM, Konte B, Kovanen L, Latvala A, Legrand LN, Maher BS, Melroy WE, Nelson EC, Reid MW, Robinson JD, Shen PH, Yang BZ, Andrews JA, Aveyard P, Beltcheva O, Brown SA, Cannon DS, Cichon S, Corley RP, Dahmen N, Degenhardt L, Foroud T, Gaebel W, Giegling I, Glatt SJ, Grucza RA, Hardin J, Hartmann AM, Heath AC, Herms S, Hodgkinson CA, Hoffmann P, Hops H, Huizinga D, Ising M, Johnson EO, Johnstone E, Kaneva RP, Kendler KS, Kiefer F, Kranzler HR, Krauter KS, Levran O, Lucae S, Lynskey MT, Maier W, Mann K, Martin NG, Mattheisen M, Montgomery GW, Müller-Myhsok B, Murphy MF, Neale MC, Nikolov MA, Nishita D, Nöthen MM, Nurnberger J, Partonen T, Pergadia ML, Reynolds M, Ridinger M, Rose RJ, Rouvinen-Lagerström N, Scherbaum N, Schmäl C, Soyka M, Stallings MC, Steffens M, Treutlein J, Tsuang M, Wall TL, Wodarz N, Yuferov V, Zill P, Bergen AW, Chen J, Cinciripini PM, Edenberg HJ, Ehringer MA, Ferrell RE, Gelernter J, Goldman D, Hewitt JK, Hopfer CJ, Iacono WG, Kaprio J, Kreek MJ, Kremensky IM, Madden PA, McGue M, Munafò MR, Philibert RA, Rietschel M, Roy A, Rujescu D, Saarikoski ST, Swan GE, Todorov AA, Vanyukov MM, Weiss RB, Bierut LJ, Saccone NL. Association of the OPRM1 Variant rs1799971 (A118G) with Non-Specific Liability to Substance Dependence in a Collaborative de novo Meta-Analysis of European-Ancestry Cohorts. Behavior Genetics 2015, 46: 151-169. PMID: 26392368, PMCID: PMC4752855, DOI: 10.1007/s10519-015-9737-3.Peer-Reviewed Original ResearchConceptsSubstance dependenceModest protective effectDSM-IV alcoholOpioid receptor geneLight smokingProtective effectNicotine dependenceAddiction liabilityDifferent addictive substancesG alleleMeta-AnalysisCocaine dependenceRs1799971Addictive substancesHuman genetic studiesReceptor genePotential functional significanceEuropean ancestry cohortsOPRM1Substance dependence riskSimilar effectsEuropean ancestry subjectsFunctional significanceAddictive behaviorsRisk
2014
The Joint Effects of ADH1B Variants and Childhood Adversity on Alcohol Related Phenotypes in African‐American and European‐American Women and Men
Sartor CE, Wang Z, Xu K, Kranzler HR, Gelernter J. The Joint Effects of ADH1B Variants and Childhood Adversity on Alcohol Related Phenotypes in African‐American and European‐American Women and Men. Alcohol Clinical And Experimental Research 2014, 38: 2907-2914. PMID: 25410943, PMCID: PMC4445128, DOI: 10.1111/acer.12572.Peer-Reviewed Original ResearchConceptsChildhood adversityAllele carriersEA menAlcohol use disorder symptomsAlcohol phenotypesRisk factorsAA womenProtective effectADH1B rs1229984Psychiatric outcomesEA womenEuropean American womenOrdinal regression analysisProtective allelesAlcohol dependenceAUD symptomsSubstance dependenceSingle nucleotide polymorphismsDisorder symptomsADH1B variantsAlcohol problemsWomenMenRegression analysisSignificant main effectDSM-5 Gambling Disorder: Prevalence and Characteristics in a Substance Use Disorder Sample
Rennert L, Denis C, Peer K, Lynch KG, Gelernter J, Kranzler HR. DSM-5 Gambling Disorder: Prevalence and Characteristics in a Substance Use Disorder Sample. Experimental And Clinical Psychopharmacology 2014, 22: 50-56. PMID: 24490711, PMCID: PMC4019046, DOI: 10.1037/a0034518.Peer-Reviewed Original ResearchConceptsSubstance Use Disorder SamplePathological gamblingGD diagnosisSemistructured psychiatric interviewFourth Edition diagnosisLogistic regression analysisGambling disorderDSM-5 diagnosisMultinomial logistic regression analysisDisorder sampleProspective studySUD sampleEdition diagnosisHigh prevalenceComorbid SUDPG criteriaPsychiatric interviewMental disordersDSM-IVSubstance dependenceDiagnosisPrevalenceStatistical ManualRegression analysisFifth edition
2013
Association of Gamma-Aminobutyric Acid A Receptor α2 Gene (GABRA2) with Alcohol Use Disorder
Li D, Sulovari A, Cheng C, Zhao H, Kranzler HR, Gelernter J. Association of Gamma-Aminobutyric Acid A Receptor α2 Gene (GABRA2) with Alcohol Use Disorder. Neuropsychopharmacology 2013, 39: 907-918. PMID: 24136292, PMCID: PMC3924525, DOI: 10.1038/npp.2013.291.Peer-Reviewed Original ResearchConceptsReceptor geneGABA receptor genesGABAA receptor genesCandidate gene association studiesSAGE data setsBonferroni-corrected thresholdGene association studiesSingle nucleotide polymorphismsAssociation studiesGenotype dataStudy of AddictionGamma-aminobutyric acidMammalian brainGenesComplex disorderGABRA2 single nucleotide polymorphismsSubstance dependenceMajor inhibitory neurotransmitterGeneticsInhibitory neurotransmitterVariantsGABA receptorsSignificant associationSubstance abuseMethamphetamine dependenceRate 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
2012
Identification of POMC Exonic Variants Associated with Substance Dependence and Body Mass Index
Wang F, Gelernter J, Kranzler HR, Zhang H. Identification of POMC Exonic Variants Associated with Substance Dependence and Body Mass Index. PLOS ONE 2012, 7: e45300. PMID: 23028917, PMCID: PMC3444488, DOI: 10.1371/journal.pone.0045300.Peer-Reviewed Original ResearchConceptsBody mass indexSubstance dependenceMass indexExact testRare variantsAfrican AmericansNormal weight groupCommon variantsFisher's exact testProopiomelanocortin geneObese groupObese subjectsExonic variantsMelanocortin peptidesEuropean AmericansLogistic regressionCommon polymorphismsOverweightRare exonic variantsVariants AssociatedPopulation-specific mannerRiskAssociationObesityGroupGABRA2 Genotype, Impulsivity, and Body Mass
Bauer LO, Yang B, Houston RJ, Kranzler HR, Gelernter J. GABRA2 Genotype, Impulsivity, and Body Mass. American Journal On Addictions 2012, 21: 404-410. PMID: 22882390, PMCID: PMC3773931, DOI: 10.1111/j.1521-0391.2012.00252.x.Peer-Reviewed Original ResearchMeSH KeywordsAdultAttention Deficit Disorder with HyperactivityBody Mass IndexCase-Control StudiesConnecticutFemaleGenotypeHumansImpulsive BehaviorMaleMiddle AgedPolymorphism, Single NucleotidePsychiatric Status Rating ScalesReceptors, GABA-ASex FactorsSubstance Abuse Treatment CentersSubstance-Related DisordersConceptsBody mass indexElevated body mass indexAssociation of BMIGABRA2 genotypeSubstance dependenceAttention-deficit/hyperactivity disorderHigh-calorie foodsPrevious pregnancyMass indexElectroencephalographic featuresRisk factorsChildhood symptomsScale scoreDrug abstinenceCalorie foodsHyperactivity disorderGenetic findingsWomenLonger durationBarratt Impulsiveness ScalePsychological indicatorsGABRA2 variantsSex differencesSecond analysisBody massPrevalence of DSM-IV and DSM-5 alcohol, cocaine, opioid, and cannabis use disorders in a largely substance dependent sample
Peer K, Rennert L, Lynch KG, Farrer L, Gelernter J, Kranzler HR. Prevalence of DSM-IV and DSM-5 alcohol, cocaine, opioid, and cannabis use disorders in a largely substance dependent sample. Drug And Alcohol Dependence 2012, 127: 215-219. PMID: 22884164, PMCID: PMC3727225, DOI: 10.1016/j.drugalcdep.2012.07.009.Peer-Reviewed Original ResearchConceptsSubstance use disordersSUD diagnosisDSM-IVDiagnosis of SUDDSM-5DSM-5 substance use disordersDSM-5 SUD diagnosesDiagnostic orphansSevere substance use disordersLimited diagnostic utilityDSM-5 diagnosisDSM-5 alcoholSemi-Structured AssessmentDSM-IV abuseDiagnostic switchLifetime presenceClinical careDiagnostic criteriaGreater prevalenceUse disordersDiagnostic utilityDependence diagnosisMental disordersDrug dependenceSubstance dependence
2011
5-HTTLPR as a potential moderator of the effects of adverse childhood experiences on risk of antisocial personality disorder
Douglas K, Chan G, Gelernter J, Arias AJ, Anton RF, Poling J, Farrer L, Kranzler HR. 5-HTTLPR as a potential moderator of the effects of adverse childhood experiences on risk of antisocial personality disorder. Psychiatric Genetics 2011, 21: 240-248. PMID: 21399568, PMCID: PMC3119731, DOI: 10.1097/ypg.0b013e3283457c15.Peer-Reviewed Original ResearchConceptsAdverse childhood eventsAntisocial personality disorderSubstance dependenceRisk factorsAA womenPersonality disorderStrong Association of the Alcohol Dehydrogenase 1B Gene (ADH1B) with Alcohol Dependence and Alcohol-Induced Medical Diseases
Li D, Zhao H, Gelernter J. Strong Association of the Alcohol Dehydrogenase 1B Gene (ADH1B) with Alcohol Dependence and Alcohol-Induced Medical Diseases. Biological Psychiatry 2011, 70: 504-512. PMID: 21497796, PMCID: PMC3142297, DOI: 10.1016/j.biopsych.2011.02.024.Peer-Reviewed Original ResearchConceptsAlcohol dependenceAlcohol dehydrogenase 1B (ADH1B) geneMedical diseasesAlcohol-induced liver diseaseStrong associationCertain Asian populationsRandom-effects modelADH1B geneLarger ORsLiver diseaseSubgroup analysisLarger sample sizeDrug dependenceSignificant associationSubstance dependenceMultiple ethnic populationsRecessive modelAsian populationsDiseaseAgitated 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 interviewsPMAAssociationComorbidities
2009
Interactive Effect of Stressful Life Events and the Serotonin Transporter 5-HTTLPR Genotype on Posttraumatic Stress Disorder Diagnosis in 2 Independent Populations
Xie P, Kranzler HR, Poling J, Stein MB, Anton RF, Brady K, Weiss RD, Farrer L, Gelernter J. Interactive Effect of Stressful Life Events and the Serotonin Transporter 5-HTTLPR Genotype on Posttraumatic Stress Disorder Diagnosis in 2 Independent Populations. JAMA Psychiatry 2009, 66: 1201-1209. PMID: 19884608, PMCID: PMC2867334, DOI: 10.1001/archgenpsychiatry.2009.153.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedBlack or African AmericanChildChild AbuseCross-Sectional StudiesDiagnostic and Statistical Manual of Mental DisordersFemaleGenetic Predisposition to DiseaseGenotypeHomozygoteHumansLife Change EventsMaleMiddle AgedPolymorphism, GeneticPsychiatric Status Rating ScalesRisk FactorsSerotonin Plasma Membrane Transport ProteinsSocial EnvironmentStress Disorders, Post-TraumaticSubstance-Related DisordersWhite PeopleConceptsAdult traumatic eventsPosttraumatic stress disorderLifetime posttraumatic stress disorderChildhood adversityStressful life eventsTraumatic eventsDSM-IV diagnostic criteriaOnset of PTSDCross-sectional studyStress disorder diagnosisPosttraumatic stress disorder (PTSD) diagnosisLogistic regression modelingLife eventsSemi-Structured AssessmentEtiology of PTSDAdverse eventsAfrican American individualsDepressive symptomsDiagnostic criteriaSerotonin transporter geneDrug dependenceTrauma exposureStress disorderGene x environment interactionsSubstance dependenceSubtypes of major depression in substance dependence
Niciu MJ, Chan G, Gelernter J, Arias AJ, Douglas K, Weiss R, Anton RF, Farrer L, Cubells JF, Kranzler HR. Subtypes of major depression in substance dependence. Addiction 2009, 104: 1700-1709. PMID: 19681804, PMCID: PMC2980795, DOI: 10.1111/j.1360-0443.2009.02672.x.Peer-Reviewed Original ResearchMeSH KeywordsAcademic Medical CentersAdolescentAdultAge FactorsAnxiety DisordersBlack or African AmericanComorbidityData Interpretation, StatisticalDepressive Disorder, MajorFemaleHispanic or LatinoHumansInterview, PsychologicalLogistic ModelsMaleRecurrenceSocioeconomic FactorsSubstance-Related DisordersSuicide, AttemptedWhite PeopleYoung AdultConceptsMajor depressive episodeSubstance dependenceMDE subtypesDrug dependenceRelated clinical featuresPotential therapeutic implicationsSubstance use disordersAcademic medical centerGreater psychiatric severitySemi-Structured AssessmentClinical featuresDepressive episodeMajor depressionMedical CenterSecondary data analysisDepressive symptomsDiagnostic criteriaPsychiatric severityTherapeutic implicationsUse disordersSubtypesAnxiety disordersPsychiatric measuresCase-control genetic studyCommunity recruitmentAdverse 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 dependabilityReportInterviewersPopulation admixture modulates risk for alcohol dependence
Zuo L, Luo X, Listman JB, Kranzler HR, Wang S, Anton RF, Blumberg HP, Stein MB, Pearlson GD, Covault J, Charney DS, van Kammen DP, Price LH, Lappalainen J, Cramer J, Krystal JH, Gelernter J. Population admixture modulates risk for alcohol dependence. Human Genetics 2009, 125: 605-613. PMID: 19306106, PMCID: PMC2777998, DOI: 10.1007/s00439-009-0647-4.Peer-Reviewed Original Research