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2025
Whole-exome sequencing study of opioid dependence offers novel insights into the contributions of exome variants
Wang L, Nuñez Y, Martínez-Magaña J, Rivera-Hernandez M, Mao Z, Brennand K, Montalvo-Ortiz J, Kranzler H, Gelernter J, Zhou H. Whole-exome sequencing study of opioid dependence offers novel insights into the contributions of exome variants. Translational Psychiatry 2025, 15: 380. PMID: 41052974, PMCID: PMC12500996, DOI: 10.1038/s41398-025-03578-y.Peer-Reviewed Original ResearchConceptsWhole-exome sequencing studiesGenetic architectureRisk variantsGene-based collapsing testCross-ancestry meta-analysisContribution of rare coding variantsGenome-wide association studiesWhole-exome sequencing dataRare Coding VariantsLow-frequency variantsParticipants of European ancestryLoss-of-functionExome variantsCross-ancestrySequence dataOpioid dependenceAssociation studiesMissense variantsTop genesEuropean ancestrySuggestive associationsRare variantsAfrican ancestryFunctional studiesYale-PennThe genetics of cannabis lifetime use
Bright U, Beck S, Galimberti M, Gupta P, Chen Y, Dao C, Nunez Y, Kranzler H, Zhou Y, Zhang Y, Choi K, Levey D, Gelernter J. The genetics of cannabis lifetime use. Neuropsychopharmacology 2025, 51: 554-564. PMID: 41044382, PMCID: PMC12824155, DOI: 10.1038/s41386-025-02255-4.Peer-Reviewed Original ResearchCannabis use disorderGenome-wide association studiesMendelian randomizationGenetic correlation analysisUse disorderGenetic architectureSubstance useGenetic basisLifetime useLocal genetic correlation analysisHealth-related phenotypesPost-GWAS analysisRisk-taking behaviorGenetic correlationsAssociation studiesGenetic populationsUse-related traitsGenetic relationshipsAssociation analysisCannabisGenetic mechanismsIntervention strategiesRisk takingIndependent variantsSexual behaviorW90. MAJOR DEPRESSIVE DISORDER AMPLIFIES THE COMBINED EFFECT OF POLYGENIC RISK AND CHILDHOOD TRAUMA ON RISK OF LIFETIME SUICIDE ATTEMPT
Fischer I, Overstreet C, Beck S, Galimberti M, Zhou H, Pietrzak R, Nunez Y, Kranzler H, Levey D, Gelernter J. W90. MAJOR DEPRESSIVE DISORDER AMPLIFIES THE COMBINED EFFECT OF POLYGENIC RISK AND CHILDHOOD TRAUMA ON RISK OF LIFETIME SUICIDE ATTEMPT. European Neuropsychopharmacology 2025, 99: 254-255. DOI: 10.1016/j.euroneuro.2025.08.447.Peer-Reviewed Original ResearchCumulative childhood traumaSuicide attemptsChildhood traumaSuicidal behaviorPolygenic riskGenetic riskAssociated with suicide attemptsEffects of suicide attemptsInfluence of genetic riskLifetime suicide attemptsEarly-life traumaProbability of suicide attemptsEarly-life adversitySubstance use disordersGWAS Meta-AnalysisEffects of genetic riskEffect of genetic liabilityAssociated with SAMDD statusLifetime MDDDepressive disorderMDD diagnosisLifetime SAPolygenic risk scoresSuicide riskMulti-ancestral genome-wide association study of clinically defined nicotine dependence reveals strong genetic correlations with other substance use disorders and health-related traits
Johnson E, Lai D, Balbona J, Miller A, Hatoum A, Deak J, Jennings M, Baranger D, Galimberti M, Sanichwankul K, Thorgeirsson T, Colbert S, Adhikari K, Docherty A, Degenhardt L, Edwards T, Fox L, Giannelis A, Jeffries P, Korhonen T, Morrison C, Nunez Y, Palviainen T, Su M, Villela P, Wetherill L, Willoughby E, Zellers S, Bierut L, Buchwald J, Copeland W, Corley R, Friedman N, Foroud T, Gillespie N, Gizer I, Heath A, Hickie I, Kaprio J, Keller M, Lee J, Lind P, Madden P, Maes H, Martin N, McGue M, Medland S, Nelson E, Pearson J, Porjesz B, Stallings M, Vrieze S, Wilhelmson K, Kranzler H, Walters R, Polimanti R, Malison R, Zhou H, Stefansson K, Sanchez-Roige S, Potenza M, Mutirangura A, Shotelersuk V, Kalayasiri R, Edenberg H, Gelernter J, Agrawal A. Multi-ancestral genome-wide association study of clinically defined nicotine dependence reveals strong genetic correlations with other substance use disorders and health-related traits. Psychological Medicine 2025, 55: e234. PMID: 40831304, PMCID: PMC12360691, DOI: 10.1017/s0033291725100883.Peer-Reviewed Original ResearchMeSH KeywordsAdultAlcoholismAsian PeopleBlack PeopleDiagnostic and Statistical Manual of Mental DisordersFemaleGenome-Wide Association StudyHumansMaleMiddle AgedNerve Tissue ProteinsPhenotypePolymorphism, Single NucleotideReceptors, NicotinicSubstance-Related DisordersTobacco Use DisorderWhite PeopleConceptsGenome-wide association studiesDiagnostic and Statistical ManualTobacco use disorderUse disorderNicotine dependenceAssociation studiesDiagnostic and Statistical Manual of Mental DisordersGenetic correlationsStatistical manual of mental disordersPolygenic scoresManual of mental disordersGenomic structural equation modelingCannabis use disorderNicotine-related phenotypesProblematic alcohol useSubstance use disordersNational Epidemiologic SurveyHealth-related traitsPositive genetic correlationIndividual diagnostic criteriaElectronic health recordsCriterion countsDSM-5Opioid use disorderPsychiatric disordersEpigenetic and genetic profiling of comorbidity patterns among substance dependence diagnoses
Pathak G, Pietrzak R, Lacobelle A, Overstreet C, Wendt F, Deak J, Friligkou E, Nunez Y, Montalvo-Ortiz J, Levey D, Kranzler H, Gelernter J, Polimanti R. Epigenetic and genetic profiling of comorbidity patterns among substance dependence diagnoses. Molecular Psychiatry 2025, 30: 4435-4443. PMID: 40247127, PMCID: PMC12343199, DOI: 10.1038/s41380-025-03031-y.Peer-Reviewed Original ResearchSubstance dependence diagnosesLatent class analysisDependence diagnosisLatent classesComorbidity patternsPolygenic scoresPolygenic overlapSD diagnosisPsychosocial traitsEpigenetic mechanismsClass analysisEpigenome-wide significant associationsEpigenome-wide association analysisCo-occurrenceTraitsIndividualsAssociated with CpG sitesAssociationComorbidityTDSD patternSubstancesEpigenome-wide changesIndividuals of European descentSignificant associationA multicenter cross-sectional study of gambling disorder among patients with methamphetamine use disorder in drug rehabilitation centers: prevalence, correlates, and network analysis
Peng P, Hao Y, Zhang X, Ma Y, Liu X, Shen D, Shen W, Zhao B, Li D, Beck S, Nunez Y, Potenza M, Gelernter J, Liu T, Yang B. A multicenter cross-sectional study of gambling disorder among patients with methamphetamine use disorder in drug rehabilitation centers: prevalence, correlates, and network analysis. Annals Of General Psychiatry 2025, 24: 12. PMID: 40033412, PMCID: PMC11877697, DOI: 10.1186/s12991-025-00546-0.Peer-Reviewed Original ResearchSemi-Structured Assessment for Drug Dependence and AlcoholismDSM-5 diagnostic criteriaGambling disorderDSM-5Antisocial personality disorderMethamphetamine use disorderSubstance use disordersDiagnostic criteriaPersonality disorderBridge symptomsDepressive episodeDrug rehabilitation centersCentral symptomsPsychiatric diagnosisGambling durationUse disorderSelf-harmChildhood experiencesMethamphetamineAlcohol useViolent experiencesDisordersManifest symptomsChinese versionMDE
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 patternsAssociationIdentifying neurofunctional domains across substance use disorders
Hartwell E, Schwandt M, Nunez Y, Wetherill R, Kember R, Wiers C, Gelernter J, Kranzler H. Identifying neurofunctional domains across substance use disorders. The American Journal Of Drug And Alcohol Abuse 2024, 50: 536-546. PMID: 39018668, DOI: 10.1080/00952990.2024.2368180.Peer-Reviewed Original ResearchSubstance use disordersHistory of abuse/neglectExploratory factor analysisExecutive functionSubstance useSemi-Structured Assessment for Drug DependenceWisconsin Card Sorting TestPersistence of substance use disordersNEO Personality InventoryCard Sorting TestFactor analysisNature of substance use disordersSix-factor modelPatterns of associationPersonality InventoryNeurofunctional domainsSorting TestDrug dependenceTargeted clinical interventionsLatent variable modelsClinical interventionsFit indicesAbuse/neglectDisordersLatent domains
2023
Multi-ancestry genome-wide association study of cannabis use disorder yields insight into disease biology and public health implications
Levey D, Galimberti M, Deak J, Wendt F, Bhattacharya A, Koller D, Harrington K, Quaden R, Johnson E, Gupta P, Biradar M, Lam M, Cooke M, Rajagopal V, Empke S, Zhou H, Nunez Y, Kranzler H, Edenberg H, Agrawal A, Smoller J, Lencz T, Hougaard D, Børglum A, Demontis D, Gaziano J, Gandal M, Polimanti R, Stein M, Gelernter J. Multi-ancestry genome-wide association study of cannabis use disorder yields insight into disease biology and public health implications. Nature Genetics 2023, 55: 2094-2103. PMID: 37985822, PMCID: PMC10703690, DOI: 10.1038/s41588-023-01563-z.Peer-Reviewed Original ResearchConceptsSingle nucleotide polymorphism-based heritabilityMulti-ancestry genome-wide association studyAssociation studiesMillion Veteran ProgramGenome-wide association studiesWide significant lociWide association studySignificant lociReference panelSmall populationDisease biologyAncestryAmerican ancestryHeritabilityVeteran ProgramNumerous medical comorbiditiesLung cancer riskRelationship analysisLociBiologyPublic health implicationsEast AsiansPublic health consequencesMedical comorbiditiesCigarette smokingPolysubstance 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 analysisParticipantsComorbiditiesDiseaseDiagnosis
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