2024
Identifying 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, ahead-of-print: 1-11. 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
2022
Genome-Wide Investigation of Maximum Habitual Alcohol Intake in US Veterans in Relation to Alcohol Consumption Traits and Alcohol Use Disorder
Deak JD, Levey DF, Wendt FR, Zhou H, Galimberti M, Kranzler HR, Gaziano JM, Stein MB, Polimanti R, Gelernter J, Muralidhar S, Moser J, Deen J, Gaziano J, Beckham J, Chang K, Tsao P, Luoh S, Casas J, Churby L, Whitbourne S, Brewer J, Brophy M, Selva L, Shayan S, Cho K, Pyarajan S, DuVall S, Connor T, Argyres D, Aslan M, Stephens B, Concato J, Gelernter J, Gleason T, Huang G, Koenen K, Marx C, Radhakrishnan K, Schork N, Stein M, Zhao H, Kaufman J, Nunez Y, Pietrzak R, Beck D, Cissell S, Crutchfield P, Lance W, Cheung K, Li Y, Sun N, Chen Q, Rajeevan N, Sayward F, Gagnon D, Harrington K, Quaden R, O'Leary T, Ramoni R. Genome-Wide Investigation of Maximum Habitual Alcohol Intake in US Veterans in Relation to Alcohol Consumption Traits and Alcohol Use Disorder. JAMA Network Open 2022, 5: e2238880. PMID: 36301540, PMCID: PMC9614582, DOI: 10.1001/jamanetworkopen.2022.38880.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesGenome-wide significant lociGenomic structural equation modelingSignificant lociAlcohol traitsAssociation studiesAfrican ancestry participantsGenome-wide investigationAncestry-specific genome-wide association studiesGenetic correlationsPsychiatric traitsLinkage disequilibrium score regressionGenetic associationStrong genetic correlationSingle nucleotide variantsGenetic architectureGenetic association studiesGenetic lociTop associationsNegative rgEuropean ancestry participantsNucleotide variantsFunctional variantsScore regressionTraitsT119. AN INTERNATIONAL AND MULTI-ANCESTRAL GENOME-WIDE ASSOCIATION STUDY META-ANALYSIS OF CANNABIS USE DISORDERS
Levey D, Galimberti M, Johnson E, Cooke M, Rajagopal V, Deak J, Zhou H, Lam M, Nunez Y, Edenberg H, Polimanti R, Lencz T, Demontis D, Stein M, Gelernter J. T119. AN INTERNATIONAL AND MULTI-ANCESTRAL GENOME-WIDE ASSOCIATION STUDY META-ANALYSIS OF CANNABIS USE DISORDERS. European Neuropsychopharmacology 2022, 63: e233. DOI: 10.1016/j.euroneuro.2022.07.415.Peer-Reviewed Original ResearchGenome-wide association study in individuals of European and African ancestry and multi-trait analysis of opioid use disorder identifies 19 independent genome-wide significant risk loci
Deak JD, Zhou H, Galimberti M, Levey DF, Wendt FR, Sanchez-Roige S, Hatoum AS, Johnson EC, Nunez YZ, Demontis D, Børglum AD, Rajagopal VM, Jennings MV, Kember RL, Justice AC, Edenberg HJ, Agrawal A, Polimanti R, Kranzler HR, Gelernter J. Genome-wide association study in individuals of European and African ancestry and multi-trait analysis of opioid use disorder identifies 19 independent genome-wide significant risk loci. Molecular Psychiatry 2022, 27: 3970-3979. PMID: 35879402, PMCID: PMC9718667, DOI: 10.1038/s41380-022-01709-1.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesGenome-wide significant risk lociAssociation studiesVariant associationsLarge-scale genome-wide association studiesGenetic correlationsSignificant risk lociPsychiatric Genomics ConsortiumMulti-trait analysisPolygenic risk score analysisSingle-variant associationsGWS lociGenetic architectureIndividuals of EuropeanGWS associationsRisk lociGene regionGenomics ConsortiumMillion Veteran ProgramSusceptibility lociAfrican ancestryLociRisk score analysisGenetic informativenessSNPs oneGenome-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 lociSubjectsClinical and behavioral correlates in adult methamphetamine users with childhood exposure to household drug and alcohol use
Rattanasumawong W, Malison R, Gelernter J, Nunez Y, Kalayasiri R. Clinical and behavioral correlates in adult methamphetamine users with childhood exposure to household drug and alcohol use. The International Journal Of Alcohol And Drug Research 2022, 9: 77-84. DOI: 10.7895/ijadr.345.Peer-Reviewed Original ResearchAntisocial personality disorderBaseline socio-demographic informationMA useCross-sectional baseline dataPersonality disorderSevere clinical presentationMethamphetamine usersSocio-demographic informationGreater subsequent useSemi-Structured AssessmentCohort studyClinical presentationAdult methamphetamine usersFamily historyChildhood exposureDrug useRespective drugsAlcohol dependenceDrug dependenceDrug typeAlcohol useFamily exposureMA usersBaseline dataSelf-harm experience
2021
Reliability and validity of DSM-IV and DSM-5 methamphetamine use disorder diagnoses using the Chinese Version of the Semi-Structured Assessment for Drug Dependence and Alcoholism (SSADDA)
Ma YJ, Wang YY, Liu MQ, Fang T, Wei ZR, Chen SB, Tan H, Nunez YZ, Zhang XJ, Hao W, Malison RT, Kranzler HR, Gelernter J, Liu TQ, Yang BZ. Reliability and validity of DSM-IV and DSM-5 methamphetamine use disorder diagnoses using the Chinese Version of the Semi-Structured Assessment for Drug Dependence and Alcoholism (SSADDA). Drug And Alcohol Dependence 2021, 229: 109047. PMID: 34710713, DOI: 10.1016/j.drugalcdep.2021.109047.Peer-Reviewed Original ResearchBi-ancestral depression GWAS in the Million Veteran Program and meta-analysis in >1.2 million individuals highlight new therapeutic directions
Levey DF, Stein MB, Wendt FR, Pathak GA, Zhou H, Aslan M, Quaden R, Harrington KM, Nuñez YZ, Overstreet C, Radhakrishnan K, Sanacora G, McIntosh AM, Shi J, Shringarpure SS, Concato J, Polimanti R, Gelernter J. Bi-ancestral depression GWAS in the Million Veteran Program and meta-analysis in >1.2 million individuals highlight new therapeutic directions. Nature Neuroscience 2021, 24: 954-963. PMID: 34045744, PMCID: PMC8404304, DOI: 10.1038/s41593-021-00860-2.Peer-Reviewed Original ResearchConceptsTranscriptome-wide association studyMillion Veteran ProgramTranscriptome-wide association study (TWAS) analysisGenomic risk lociComplex psychiatric traitsGenetic architectureRisk lociGene expressionAssociation studiesLikely pathogenicityPsychiatric traitsVeteran ProgramNew therapeutic directionEuropean ancestryNew insightsAncestryUK BiobankAfrican ancestrySubstantial replicationExpressionLarge independent cohortsGWASTherapeutic directionsGenesLociSex-stratified gene-by-environment genome-wide interaction study of trauma, posttraumatic-stress, and suicidality
Wendt FR, Pathak GA, Levey DF, Nuñez YZ, Overstreet C, Tyrrell C, Adhikari K, De Angelis F, Tylee DS, Goswami A, Krystal JH, Abdallah CG, Stein MB, Kranzler HR, Gelernter J, Polimanti R. Sex-stratified gene-by-environment genome-wide interaction study of trauma, posttraumatic-stress, and suicidality. Neurobiology Of Stress 2021, 14: 100309. PMID: 33665242, PMCID: PMC7905234, DOI: 10.1016/j.ynstr.2021.100309.Peer-Reviewed Original ResearchGenome-wide interaction studyRisk lociChromatin interaction profilesExtracellular matrix biologyGene-based analysisMatrix biologyMolecular basisTranscriptomic profilesInteraction studiesMultivariate geneGenetic perspectiveSNP effectsSuicidal behavior severityLociNovel targetGenesInteraction profilesSynaptic plasticityCellsInteractorsGenetic riskBiologyStressGxEIndependent cohortEpigenomic Profiles of African-American Transthyretin Val122Ile Carriers Reveals Putatively Dysregulated Amyloid Mechanisms
Pathak GA, Wendt FR, De Lillo A, Nunez YZ, Goswami A, De Angelis F, Fuciarelli M, Kranzler HR, Gelernter J, Polimanti R. Epigenomic Profiles of African-American Transthyretin Val122Ile Carriers Reveals Putatively Dysregulated Amyloid Mechanisms. Circulation Genomic And Precision Medicine 2021, 14: e003011. PMID: 33428857, PMCID: PMC7887108, DOI: 10.1161/circgen.120.003011.Peer-Reviewed Original ResearchAmyloidosisATP Binding Cassette Transporter 1Black or African AmericanDNA MethylationEpigenomicsGene Regulatory NetworksGenome-Wide Association StudyHeart DiseasesHumansKv1.6 Potassium ChannelPhosphoproteinsPolymorphism, Single NucleotidePrealbuminQuantitative Trait LociUbiquitin-Conjugating EnzymesMulti-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
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 RevisionDiagnostic Reliability and Validity of the Semi-Structured Assessment for Drug Dependence and Alcoholism (SSADDA) Chinese Version
Yang BZ, Wang LJ, Huang MC, Wang SC, Tsai MC, Huang YC, Nuñez YZ, Ng MH, Kranzler HR, Gelernter J, Chen CK. Diagnostic Reliability and Validity of the Semi-Structured Assessment for Drug Dependence and Alcoholism (SSADDA) Chinese Version. Complex Psychiatry 2020, 6: 62-67. PMID: 34882761, PMCID: PMC7923924, DOI: 10.1159/000511606.Peer-Reviewed Original ResearchSD diagnosisSemi-Structured AssessmentTest-retest reliabilityDependence diagnosisDrug dependenceΚ statisticDiagnostic reliabilityStructured Clinical InterviewCohen κ statisticChance-corrected agreementClinician versionSubstance dependence diagnosesNicotine dependencePsychiatric disordersClinical InterviewAlcohol dependenceDSM-IVDiagnosisSubstance useChinese versionOpioidsValid instrumentConcurrent validityKetamineMethamphetamineComplex Multi-Environment Gene Interactions at the Basis of the Interplay Between Polysubstance Abuse and Suicide Behaviors
Polimanti R, Levey D, Pathak G, Wendt F, Nunez Y, Kranzler H, Stein M, Gelernter J. Complex Multi-Environment Gene Interactions at the Basis of the Interplay Between Polysubstance Abuse and Suicide Behaviors. Biological Psychiatry 2020, 87: s155. DOI: 10.1016/j.biopsych.2020.02.411.Peer-Reviewed Original Research
2019
Genome‐wide scan identifies opioid overdose risk locus close to MCOLN1
Cheng Z, Yang B, Zhou H, Nunez Y, Kranzler HR, Gelernter J. Genome‐wide scan identifies opioid overdose risk locus close to MCOLN1. Addiction Biology 2019, 25: e12811. PMID: 31362332, PMCID: PMC7485539, DOI: 10.1111/adb.12811.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesMucolipin-1Expression profilesGenome-wide significant signalsAssociation studiesPost-GWAS analysisWide association studyDrug repositioning analysisCation channel activityFunctional categoriesConnectivity Map databaseDrug targetsRisk genesGenesChannel activityPatatin-like phospholipaseNetwork analysisPNPLA6Significant signalEuropean AmericansSalivary 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 ResearchIncreased Risk of Multiple Outpatient Surgeries in African-American Carriers of Transthyretin Val122Ile Mutation Is Modulated by Non-Coding Variants
Polimanti R, Nuñez YZ, Gelernter J. Increased Risk of Multiple Outpatient Surgeries in African-American Carriers of Transthyretin Val122Ile Mutation Is Modulated by Non-Coding Variants. Journal Of Clinical Medicine 2019, 8: 269. PMID: 30813263, PMCID: PMC6406512, DOI: 10.3390/jcm8020269.Peer-Reviewed Original ResearchGenetic associations with suicide attempt severity and genetic overlap with major depression
Levey DF, Polimanti R, Cheng Z, Zhou H, Nuñez YZ, Jain S, He F, Sun X, Ursano RJ, Kessler RC, Smoller JW, Stein MB, Kranzler HR, Gelernter J. Genetic associations with suicide attempt severity and genetic overlap with major depression. Translational Psychiatry 2019, 9: 22. PMID: 30655502, PMCID: PMC6336846, DOI: 10.1038/s41398-018-0340-2.Peer-Reviewed Original ResearchConceptsGWS associationsGenome-wide significant signalsCircadian clock regulationWide association studyGenetic overlapCatabolism of tyrosineClock regulationFirst GWASSignificant genetic overlapDiscovery GWASChromosome 12Large GWASMolecular mechanismsAssociation studiesChromosome 15Chromosome 18Genetic influencesDiscovery sampleGenetic associationSuicide attempt severityReplication analysisGWASAnaerobic energy productionGenetic risk factorsPolygenic risk scores