2024
Genetic contribution to the comorbidity between attention-deficit/hyperactivity disorder and substance use disorders
Koller D, Mitjans M, Kouakou M, Friligkou E, Cabrera-Mendoza B, Deak J, Llonga N, Pathak G, Stiltner B, Løkhammer S, Levey D, Zhou H, Hatoum A, Kember R, Kranzler H, Stein M, Corominas R, Demontis D, Artigas M, Ramos-Quiroga J, Gelernter J, Ribasés M, Cormand B, Polimanti R. Genetic contribution to the comorbidity between attention-deficit/hyperactivity disorder and substance use disorders. Psychiatry Research 2024, 333: 115758. PMID: 38335780, PMCID: PMC11157987, DOI: 10.1016/j.psychres.2024.115758.Peer-Reviewed Original ResearchConceptsUse disorderGenome-wide association studiesGenomic structural equation modelingCannabis use disorderAlcohol Use Disorders Identification TestAttention-deficit/hyperactivity disorderAlcohol use disorderProblematic alcohol useSubstance use disordersTwo-sample Mendelian randomization analysisLinkage disequilibrium score regression analysisDisorders Identification TestMendelian randomization analysisAssociated with increased oddsOdds of ADHDOpioid use disorderAttention-deficit/hyperactivityGWAS meta-analysesAlcohol dependenceStructural equation modelingNicotine dependenceInvestigate genetic correlationsADHDPolygenic riskStrength of evidence
2022
Genome-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
2020
Diagnostic 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 validityKetamineMethamphetamine
2019
Salivary 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 ResearchEvidence of causal effect of major depression on alcohol dependence: findings from the psychiatric genomics consortium
Polimanti R, Peterson RE, Ong JS, MacGregor S, Edwards AC, Clarke TK, Frank J, Gerring Z, Gillespie NA, Lind PA, Maes HH, Martin NG, Mbarek H, Medland SE, Streit F, Agrawal A, Edenberg H, Kendler K, Lewis C, Sullivan P, Wray N, Gelernter J, Derks E. Evidence of causal effect of major depression on alcohol dependence: findings from the psychiatric genomics consortium. Psychological Medicine 2019, 49: 1218-1226. PMID: 30929657, PMCID: PMC6565601, DOI: 10.1017/s0033291719000667.Peer-Reviewed Original ResearchConceptsMajor depressionAlcohol dependenceAlcohol consumptionPsychiatric Genomics ConsortiumImportant public health concernMendelian randomizationPublic health concernUK BiobankClinical associationsHealth concernMR analysisReverse causationCausal roleNon-significant resultsCausal relationshipGenetic liabilityGenomics ConsortiumLinkage disequilibrium score regressionIntervention efforts
2018
Genetic influences on eight psychiatric disorders based on family data of 4 408 646 full and half-siblings, and genetic data of 333 748 cases and controls
Pettersson E, Lichtenstein P, Larsson H, Song J, Agrawal A, Børglum A, Bulik C, Daly M, Davis L, Demontis D, Edenberg H, Grove J, Gelernter J, Neale B, Pardiñas A, Stahl E, Walters J, Walters R, Sullivan P, Posthuma D, Polderman T. Genetic influences on eight psychiatric disorders based on family data of 4 408 646 full and half-siblings, and genetic data of 333 748 cases and controls. Psychological Medicine 2018, 49: 1166-1173. PMID: 30221610, PMCID: PMC6421104, DOI: 10.1017/s0033291718002039.Peer-Reviewed Original ResearchMeSH KeywordsAdultAlcoholismAnorexia NervosaAttention Deficit Disorder with HyperactivityAutism Spectrum DisorderBipolar DisorderCase-Control StudiesCohort StudiesDepressive Disorder, MajorFamilyFemaleGene-Environment InteractionGenotypeHumansMaleMental DisordersObsessive-Compulsive DisorderQuantitative Trait, HeritableSchizophreniaSchizophrenic PsychologySiblingsSweden
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 disorderGenomewide Association Study of Alcohol Dependence Identifies Risk Loci Altering Ethanol‐Response Behaviors in Model Organisms
Adkins AE, Hack LM, Bigdeli TB, Williamson VS, McMichael GO, Mamdani M, Edwards AC, Aliev F, Chan RF, Bhandari P, Raabe RC, Alaimo JT, Blackwell GG, Moscati A, Poland RS, Rood B, Patterson DG, Walsh D, Consortium C, Whitfield JB, Zhu G, Montgomery GW, Henders AK, Martin NG, Heath AC, Madden PAF, Frank J, Ridinger M, Wodarz N, Soyka M, Zill P, Ising M, Nöthen MM, Kiefer F, Rietschel M, Consortium T, Gelernter J, Sherva R, Koesterer R, Almasy L, Zhao H, Kranzler HR, Farrer LA, Maher BS, Prescott CA, Dick DM, Bacanu SA, Mathies LD, Davies AG, Vladimirov VI, Grotewiel M, Bowers MS, Bettinger JC, Webb BT, Miles MF, Kendler KS, Riley BP. Genomewide Association Study of Alcohol Dependence Identifies Risk Loci Altering Ethanol‐Response Behaviors in Model Organisms. Alcohol Clinical And Experimental Research 2017, 41: 911-928. PMID: 28226201, PMCID: PMC5404949, DOI: 10.1111/acer.13362.Peer-Reviewed Original ResearchConceptsModel organismsGenomewide association studiesLoss of functionAssociation studiesPrimate-specific genesAcute functional toleranceOrthologous genesCaenorhabditis elegansSuggestive signalsOrthologsExpression differencesGene expressionCOL6A3 expressionGenesAlcohol dependenceNucleus accumbensKLF12 expressionSuggestive associationElegansCOL6A3AD liabilityPotential involvementMultiple brain functionsEtOH sensitivityKLF12Predictors of tanning dependence in white non‐Hispanic females and males
Cartmel B, Bale AE, Mayne ST, Gelernter JE, DeWan AT, Spain P, Leffell DJ, Pagoto S, Ferrucci LM. Predictors of tanning dependence in white non‐Hispanic females and males. Journal Of The European Academy Of Dermatology And Venereology 2017, 31: 1223-1228. PMID: 28129487, PMCID: PMC5522341, DOI: 10.1111/jdv.14138.Peer-Reviewed Original ResearchConceptsEarly-onset basal cell carcinomaCase-control studyBasal cell carcinomaWhite non-Hispanic femalesSymptoms of dependenceCell carcinomaNon-Hispanic femalesAlcohol dependenceMental disordersAppropriate interventionsHost factorsNon-HispanicsStatistical ManualMultivariate modelIndoor tanningSignificant predictorsOnline surveyFourth EditionPredictorsEuropean ancestryQuestionnaireEye openerEye colorParticipantsCarcinoma
2016
The Interplay Between Risky Sexual Behaviors and Alcohol Dependence: Genome-Wide Association and Neuroimaging Support for LHPP as a Risk Gene
Polimanti R, Wang Q, Meda SA, Patel KT, Pearlson GD, Zhao H, Farrer LA, Kranzler HR, Gelernter J. The Interplay Between Risky Sexual Behaviors and Alcohol Dependence: Genome-Wide Association and Neuroimaging Support for LHPP as a Risk Gene. Neuropsychopharmacology 2016, 42: 598-605. PMID: 27531626, PMCID: PMC5240175, DOI: 10.1038/npp.2016.153.Peer-Reviewed Original ResearchConceptsRisky sexual behaviorAlcohol dependenceLow-frequency fluctuation (ALFF) analysisLeft superior frontal gyrusMultiple sexual partnersDSM-IV criteriaSexual behaviorMagnetic Resonance Imaging AnalysisAnterior cingulate regionsSuperior frontal gyrusMonetary incentive delay taskLifetime alcohol dependenceIncentive delay taskRight amygdalaClinical relevanceSTD riskUnprotected sexBrain circuitryFunctional magnetic resonance imaging (fMRI) analysisCingulate regionsSexual partnersFrequency fluctuation analysisFrontal gyrusGenetic findingsReduced activation
2015
Genome‐wide association study of body mass index in subjects with alcohol dependence
Polimanti R, Zhang H, Smith AH, Zhao H, Farrer LA, Kranzler HR, Gelernter J. Genome‐wide association study of body mass index in subjects with alcohol dependence. Addiction Biology 2015, 22: 535-549. PMID: 26458734, PMCID: PMC5102811, DOI: 10.1111/adb.12317.Peer-Reviewed Original ResearchMeSH KeywordsAcid Anhydride HydrolasesAdenylyl CyclasesAdultAlcoholismAldehyde DehydrogenaseAldehyde Dehydrogenase 1 FamilyAlpha-Ketoglutarate-Dependent Dioxygenase FTOBlack or African AmericanBody Mass IndexCell Adhesion MoleculesDNA-Binding ProteinsFemaleGenome-Wide Association StudyHSP40 Heat-Shock ProteinsHumansMaleMembrane ProteinsMiddle AgedNerve Tissue ProteinsObesityPolymorphism, Single NucleotideRab GTP-Binding ProteinsRetinal DehydrogenaseRNA, Long NoncodingTranscription FactorsWhite PeopleConceptsBody mass indexAlcohol dependenceMass indexBirth sizeAfrican AmericansDrug dependenceSemi-Structured AssessmentBody massEye color: A potential indicator of alcohol dependence risk in European Americans
Sulovari A, Kranzler HR, Farrer LA, Gelernter J, Li D. Eye color: A potential indicator of alcohol dependence risk in European Americans. American Journal Of Medical Genetics Part B Neuropsychiatric Genetics 2015, 168: 347-353. PMID: 25921801, DOI: 10.1002/ajmg.b.32316.Peer-Reviewed Original ResearchConceptsAlcohol dependenceLight-eyed individualsDark-eyed individualsPopulation-based studyLight eye colorBlue eye colorEvidence of associationEye colorRisk factorsEtiological factorsHigh prevalenceEye color geneLogistic regressionAD-associated genesMore alcoholArchival samplesColor genesAssociationEuropean ancestry subjectsReceptor gene clusterIndividualsStratificationBrown eye colorFurther characterizationAssociation studiesPolygenic risk for alcohol dependence associates with alcohol consumption, cognitive function and social deprivation in a population‐based cohort
Clarke T, Smith AH, Gelernter J, Kranzler HR, Farrer LA, Hall LS, Fernandez‐Pujals A, MacIntyre DJ, Smith BH, Hocking LJ, Padmanabhan S, Hayward C, Thomson PA, Porteous DJ, Deary IJ, McIntosh AM. Polygenic risk for alcohol dependence associates with alcohol consumption, cognitive function and social deprivation in a population‐based cohort. Addiction Biology 2015, 21: 469-480. PMID: 25865819, PMCID: PMC4600406, DOI: 10.1111/adb.12245.Peer-Reviewed Original ResearchConceptsCognitive abilitiesCognitive functionAlcohol dependenceCognitive impairmentPrevalence of problemsPolygenic risk scoresOnset of dependenceCognitive dysfunctionFamily Health StudyScottish Family Health StudySocial deprivationSignificant negative associationHeavy drinkingGenetic overlapNegative associationImpairmentPhenotypic associationsAlcohol consumptionCognitionDeprivationFuture workPresent studyAbilityAssociationDrinking
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 effectNf1 Regulates Alcohol Dependence-Associated Excessive Drinking and Gamma-Aminobutyric Acid Release in the Central Amygdala in Mice and Is Associated with Alcohol Dependence in Humans
Repunte-Canonigo V, Herman MA, Kawamura T, Kranzler HR, Sherva R, Gelernter J, Farrer LA, Roberto M, Sanna PP. Nf1 Regulates Alcohol Dependence-Associated Excessive Drinking and Gamma-Aminobutyric Acid Release in the Central Amygdala in Mice and Is Associated with Alcohol Dependence in Humans. Biological Psychiatry 2014, 77: 870-879. PMID: 25483400, PMCID: PMC4428692, DOI: 10.1016/j.biopsych.2014.07.031.Peer-Reviewed Original ResearchConceptsChronic intermittent ethanol vapor exposureGABA releaseWild-type miceGamma-aminobutyric acidAlcohol dependenceCentral amygdalaGamma-aminobutyric acid releaseIntermittent ethanol vapor exposureExcessive drinkingMouse central amygdalaEthanol vapor exposureHeterozygous null miceAlcohol dependence riskInduction of dependenceAlcohol drinkingAlcohol-related behaviorsDependent drinkingBinge drinkingTranslational investigationsNull miceCentral nucleusType 1 geneMiceAmygdalaAcid releasePharmacogenetics of naltrexone and disulfiram in alcohol dependent, dually diagnosed veterans
Arias AJ, Gelernter J, Gueorguieva R, Ralevski E, Petrakis IL. Pharmacogenetics of naltrexone and disulfiram in alcohol dependent, dually diagnosed veterans. American Journal On Addictions 2014, 23: 288-293. PMID: 24724887, PMCID: PMC4600600, DOI: 10.1111/j.1521-0391.2014.12102.x.Peer-Reviewed Original ResearchMeSH KeywordsAlcohol DeterrentsAlcoholismDiagnosis, Dual (Psychiatry)DisulfiramDopamine beta-HydroxylaseDrug Therapy, CombinationFemaleGenotypeHeterozygoteHumansMaleMental DisordersMiddle AgedNaltrexoneNarcotic AntagonistsPolymorphism, Single NucleotideReceptors, Opioid, muTreatment OutcomeVeteransWhite PeopleConceptsAllele carriersHeavy drinkingCo-occurring alcohol dependenceT allele carriersAlcohol-dependent subjectsAD treatment responseTreatment of individualsPrimary outcomePharmacogenetic interactionsHigher overall rateTreatment responseAxis INaltrexoneT carriersEuropean-American subjectsOPRM1 rs1799971Favorable responseMore abstinenceAlcohol dependenceDependent subjectsDBH rs1611115DisulfiramGenotyped subjectsAbstinenceLess drinkingTopiramate Treatment for Heavy Drinkers: Moderation by a GRIK1 Polymorphism
Kranzler HR, Covault J, Feinn R, Armeli S, Tennen H, Arias AJ, Gelernter J, Pond T, Oncken C, Kampman KM. Topiramate Treatment for Heavy Drinkers: Moderation by a GRIK1 Polymorphism. American Journal Of Psychiatry 2014, 171: 445-452. PMID: 24525690, PMCID: PMC3997125, DOI: 10.1176/appi.ajp.2013.13081014.Peer-Reviewed Original ResearchConceptsHeavy drinking daysHeavy drinkersTopiramate treatmentDaily doseHeavy drinkingTopiramate's effectsDrinking daysAbstinent daysUse of topiramateMaximal daily doseWeeks of treatmentC allele homozygotesPersonalized treatment optionsEnzyme γ-glutamyl transpeptidasePlacebo groupΓ-glutamyl transpeptidaseTreatment optionsTreatment completionPharmacogenetic findingsTreatment goalsAlcohol-related problemsKainate receptorsTreatment groupsBrief counselingAlcohol dependenceThe α-endomannosidase gene (MANEA) is associated with panic disorder and social anxiety disorder
Jensen KP, Stein MB, Kranzler HR, Yang BZ, Farrer LA, Gelernter J. The α-endomannosidase gene (MANEA) is associated with panic disorder and social anxiety disorder. Translational Psychiatry 2014, 4: e353-e353. PMID: 24473444, PMCID: PMC3905232, DOI: 10.1038/tp.2013.122.Peer-Reviewed Original ResearchConceptsPanic disorderAnxiety disordersCocaine-induced paranoiaAnxiety disorder casesWhole blood cellsPsychiatric disorder riskWarrants further investigationAfrican American subjectsComorbid drugPD casesPsychiatric disordersAlcohol dependenceBrain tissueCocaine useBehavioral effectsBlood cellsClinical potentialGene variantsDisordersDisorder casesSingle nucleotide polymorphismsDisorder riskIndependent samplesPsychiatric phenotypesFurther investigation
2013
Pharmacogenetics of naltrexone and disulfiram in alcohol dependent, dually diagnosed veterans
Arias A, Gelernter J, Gueorguieva R, Ralevski E, Petrakis I. Pharmacogenetics of naltrexone and disulfiram in alcohol dependent, dually diagnosed veterans. American Journal On Addictions 2013 DOI: 10.1111/j.1521-0391.2013.12102.x.Peer-Reviewed Original ResearchAllele carriersHeavy drinkingCo-occurring alcohol dependenceT allele carriersAlcohol-dependent subjectsAD treatment responseTreatment of individualsPrimary outcomePharmacogenetic interactionsHigher overall rateTreatment responseAxis INaltrexoneT carriersEuropean-American subjectsFavorable responseOPRM1 rs1799971More abstinenceAlcohol dependenceDependent subjectsDBH rs1611115DisulfiramGenotyped subjectsAbstinenceLess drinking