2024
T4. RELATIONSHIP OF GENETICALLY-INDEXED PHYSICAL ACTIVITY WITH MENTAL DISORDERS
Galimberti M, Gupta P, Deak J, Dao C, Nitin R, Zhou H, Harrington K, Na P, Topiwala A, Davis L, Gaziano M, Levey D, Stein M, Gelernter J. T4. RELATIONSHIP OF GENETICALLY-INDEXED PHYSICAL ACTIVITY WITH MENTAL DISORDERS. European Neuropsychopharmacology 2024, 87: 157-158. DOI: 10.1016/j.euroneuro.2024.08.314.Peer-Reviewed Original ResearchProtective effect of PAMental health traitsMillion Veteran ProgramEffects of PAGenome-wide association studiesPhysical activityLocal genetic correlationAlcohol consumptionPosttraumatic stress disorderSmoking initiationLeisure time PARelationship of PAUse disorderMental health outcomesPsychiatric disordersSelf-reported informationSubstance useAttention-deficit/hyperactivity disorderGenetic correlation analysisLocal genetic correlation analysisTime PAGenome-wide association study statisticsHealth traitsMR analysisResults PAF96. ALCOHOL USE AND DEMENTIA IN DIVERSE POPULATIONS
Topiwala A, Levey D, Zhou H, Deak J, Adhikari K, Ebmeier K, Bell S, Burgess S, Nichols T, Gaziano M, Stein M, Gelernter J. F96. ALCOHOL USE AND DEMENTIA IN DIVERSE POPULATIONS. European Neuropsychopharmacology 2024, 87: 256-257. DOI: 10.1016/j.euroneuro.2024.08.507.Peer-Reviewed Original ResearchMillion Veteran ProgramDementia riskMendelian randomizationDementia casesAlcohol usePrevalence of alcohol use disordersImpact of alcohol useRandom-effects meta-analysisAlcohol use disorder prevalenceProspective cohort studyStandard deviation increaseObservational associationsUK BiobankVeteran ProgramLevels of drinkingPopulation prevalenceAlcohol consumptionAlcohol use disorderCohort studyDisorder prevalenceDementiaDependent drinkersDose-response relationshipGenetic associationLight drinkersA phenome-wide association and Mendelian randomisation study of alcohol use variants in a diverse cohort comprising over 3 million individuals
Jennings M, Martínez-Magaña J, Courchesne-Krak N, Cupertino R, Vilar-Ribó L, Bianchi S, Hatoum A, Atkinson E, Giusti-Rodriguez P, Montalvo-Ortiz J, Gelernter J, Artigas M, 23andMe I, Aslibekyan S, Auton A, Babalola E, Bell R, Bielenberg J, Bryc K, Bullis E, Coker D, Partida G, Dhamija D, Das S, Elson S, Eriksson N, Filshtein T, Fitch A, Fletez-Brant K, Fontanillas P, Freyman W, Granka J, Heilbron K, Hernandez A, Hicks B, Hinds D, Jewett E, Jiang Y, Kukar K, Kwong A, Lin K, Llamas B, Lowe M, McCreight J, McIntyre M, Micheletti S, Moreno M, Nandakumar P, Nguyen D, Noblin E, O'Connell J, Petrakovitz A, Poznik G, Reynoso A, Schumacher M, Shastri A, Shelton J, Shi J, Shringarpure S, Su Q, Tat S, Tchakouté C, Tran V, Tung J, Wang X, Wang W, Weldon C, Wilton P, Wong C, Elson S, Edenberg H, Fontanillas P, Palmer A, Sanchez-Roige S. A phenome-wide association and Mendelian randomisation study of alcohol use variants in a diverse cohort comprising over 3 million individuals. EBioMedicine 2024, 103: 105086. PMID: 38580523, PMCID: PMC11121167, DOI: 10.1016/j.ebiom.2024.105086.Peer-Reviewed Original ResearchConceptsMultiple domains of healthDomains of healthEffects of alcohol consumptionAlcohol consumptionHealth outcomesPhenome-wide association studyAlcohol-related behaviorsCardio-metabolic healthPotential causal effectMendelian randomisation studiesGenome-wide association studiesPhenome-wide associationMR analysisPheWAS associationsMultiple domainsHypothesis-free approachPreventive medicineDiverse cohortPheWASAssociation studiesHealthReproductive healthAlcohol behaviorConsequences of drinkingEuropean cohort
2023
Positive personality traits moderate persistent high alcohol consumption, determined by polygenic risk in U.S. military veterans: results from a 10-year, population-based, observational cohort study
Na P, Zhou H, Montalvo-Ortiz J, Cabrera-Mendoza B, Petrakis I, Krystal J, Polimanti R, Gelernter J, Pietrzak R. Positive personality traits moderate persistent high alcohol consumption, determined by polygenic risk in U.S. military veterans: results from a 10-year, population-based, observational cohort study. Psychological Medicine 2023, 53: 7893-7901. PMID: 37642191, DOI: 10.1017/s003329172300199x.Peer-Reviewed Original ResearchTrajectories of alcohol consumption in U.S. military veterans: Results from a 10-year population-based longitudinal study
Na P, Montalvo-Ortiz J, Petrakis I, Krystal J, Polimanti R, Gelernter J, Pietrzak R. Trajectories of alcohol consumption in U.S. military veterans: Results from a 10-year population-based longitudinal study. Drug And Alcohol Dependence 2023, 246: 109833. PMID: 36963160, PMCID: PMC10811960, DOI: 10.1016/j.drugalcdep.2023.109833.Peer-Reviewed Original ResearchConceptsAlcohol consumption groupCurrent mental health treatmentDysphoric arousal symptomsMental health treatmentUS veteransAlcohol consumptionHealth treatmentConsumption groupArousal symptomsYounger agePopulation-based longitudinal studyPublic health problemLongitudinal studyExcessive alcohol consumptionAlcohol use disorderPosttraumatic stress disorderU.S. military veteransMedical comorbiditiesChronic courseNational HealthClose monitoringUse disordersHealth problemsVeterans StudyStress disorder
2022
Associations between moderate alcohol consumption, brain iron, and cognition in UK Biobank participants: Observational and mendelian randomization analyses
Topiwala A, Wang C, Ebmeier KP, Burgess S, Bell S, Levey DF, Zhou H, McCracken C, Roca-Fernández A, Petersen SE, Raman B, Husain M, Gelernter J, Miller KL, Smith SM, Nichols TE. Associations between moderate alcohol consumption, brain iron, and cognition in UK Biobank participants: Observational and mendelian randomization analyses. PLOS Medicine 2022, 19: e1004039. PMID: 35834561, PMCID: PMC9282660, DOI: 10.1371/journal.pmed.1004039.Peer-Reviewed Original ResearchConceptsAlcohol use disorderHigh brain ironModerate alcohol consumptionBrain ironAlcohol consumptionAlcohol intakeUse disordersSubstantia nigraAlcohol-related cognitive declineIron depositionBrain regionsSusceptibility-weighted magnetic resonanceIron accumulationIron levelsBrain iron depositionBrain iron levelsSystemic iron levelsSystemic iron storesAlcohol-related cognitive deficitsBasal ganglia ironElevated liver ironMendelian randomizationWeekly alcohol consumptionUK Biobank participantsExecutive functionGenome-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 lociSubjectsPost‐treatment effects of topiramate on alcohol‐related outcomes: A combined analysis of two placebo‐controlled trials
Kranzler HR, Feinn R, Pond T, Hartwell E, Gelernter J, Crist RC, Witkiewitz K. Post‐treatment effects of topiramate on alcohol‐related outcomes: A combined analysis of two placebo‐controlled trials. Addiction Biology 2022, 27: e13130. PMID: 35229945, PMCID: PMC9257958, DOI: 10.1111/adb.13130.Peer-Reviewed Original ResearchConceptsAlcohol use disorderPost-treatment periodAlcohol-related outcomesAlcohol-related problemsTopiramate's effectsSingle nucleotide polymorphismsPlacebo-controlled trialPrimary treatment outcomeOptimal treatment durationSelf-reported alcohol consumptionTrial of topiramatePost-treatment effectsTopiramate groupPlacebo groupSecond RCTMedication effectsTreatment outcomesProblematic alcohol useTopiramateTreatment durationUse disordersAlcohol consumptionΓ-glutamyltransferaseRobust effectGenotype groups
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
Author Correction: Genome-wide association study of alcohol consumption and use disorder in 274,424 individuals from multiple populations
Kranzler HR, Zhou H, Kember RL, Smith RV, Justice AC, Damrauer S, Tsao PS, Klarin D, Baras A, Reid J, Overton J, Rader DJ, Cheng Z, Tate JP, Becker WC, Concato J, Xu K, Polimanti R, Zhao H, Gelernter J. Author Correction: Genome-wide association study of alcohol consumption and use disorder in 274,424 individuals from multiple populations. Nature Communications 2019, 10: 2275. PMID: 31101824, PMCID: PMC6525240, DOI: 10.1038/s41467-019-10254-5.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
2016
Alcohol Misuse and Co‐Occurring Mental Disorders Among New Soldiers in the U.S. Army
Stein MB, Campbell‐Sills L, Gelernter J, He F, Heeringa SG, Nock MK, Sampson NA, Sun X, Jain S, Kessler RC, Ursano RJ, Collaborators S. Alcohol Misuse and Co‐Occurring Mental Disorders Among New Soldiers in the U.S. Army. Alcohol Clinical And Experimental Research 2016, 41: 139-148. PMID: 27883222, PMCID: PMC5205544, DOI: 10.1111/acer.13269.Peer-Reviewed Original ResearchConceptsAlcohol use disorderBinge drinkingAlcohol misuseMental disordersHeavy drinkingAdverse outcomesAssociation of AUDSuicidal ideationProbable alcohol use disorderOnset of AUDSubstance abuse/dependencePrior alcohol use disordersPrior mental disordersLifetime alcohol use disorderStrong bidirectional associationLifetime alcohol consumptionAbuse/dependenceCohort of soldiersBasic combat trainingDiscrete-time survival analysisOverall burdenUse disordersAlcohol consumptionDrug useSurvival analysis
2015
Ethanol Upregulates NMDA Receptor Subunit Gene Expression in Human Embryonic Stem Cell-Derived Cortical Neurons
Xiang Y, Kim KY, Gelernter J, Park IH, Zhang H. Ethanol Upregulates NMDA Receptor Subunit Gene Expression in Human Embryonic Stem Cell-Derived Cortical Neurons. PLOS ONE 2015, 10: e0134907. PMID: 26266540, PMCID: PMC4534442, DOI: 10.1371/journal.pone.0134907.Peer-Reviewed Original ResearchConceptsCortical neuronsReceptor subunit gene expressionNeuron-specific biomarkerReverse transcription-quantitative polymerase chain reactionNMDA receptor subunit gene expressionChronic alcohol consumptionHuman brain cellsAlcohol-responsive genesNMDA receptor genesCalcium channel activityLive human brainQuantitative polymerase chain reactionSubunit gene expressionWithdrawal treatmentPolymerase chain reactionExpression changesEthanol exposureAlcohol abuseMultiple comparison correctionBrain cellsGene expression alterationsAlcohol consumptionNeuronal functionAlcohol metabolismNeuronsPolygenic 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
2013
Childhood adversity moderates the effect of ADH1B on risk for alcohol‐related phenotypes in Jewish Israeli drinkers
Meyers JL, Shmulewitz D, Wall MM, Keyes KM, Aharonovich E, Spivak B, Weizman A, Frisch A, Edenberg HJ, Gelernter J, Grant BF, Hasin D. Childhood adversity moderates the effect of ADH1B on risk for alcohol‐related phenotypes in Jewish Israeli drinkers. Addiction Biology 2013, 20: 205-214. PMID: 24164917, PMCID: PMC3999313, DOI: 10.1111/adb.12102.Peer-Reviewed Original ResearchConceptsADH1B rs1229984Childhood adversityAUD severityAlcohol consumptionHeavy alcohol consumptionEnvironmental risk factorsAdult household residentsEarly life adversityMaximum drinksAUD symptom severityRisk factorsAlcohol metabolismSymptom severityLife adversityAlcohol-related phenotypesSeverityDisorder severityGenetic vulnerability
2011
A CRHR1 haplotype moderates the effect of adverse childhood experiences on lifetime risk of major depressive episode in African‐American women
Kranzler HR, Feinn R, Nelson EC, Covault J, Anton RF, Farrer L, Gelernter J. A CRHR1 haplotype moderates the effect of adverse childhood experiences on lifetime risk of major depressive episode in African‐American women. American Journal Of Medical Genetics Part B Neuropsychiatric Genetics 2011, 156: 960-968. PMID: 21998007, PMCID: PMC3227028, DOI: 10.1002/ajmg.b.31243.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAlcohol DrinkingBlack or African AmericanChildChild AbuseDepressionDepressive Disorder, MajorFemaleGene FrequencyGenetic Predisposition to DiseaseHaplotypesHumansMiddle AgedPolymorphism, Single NucleotideReceptors, Corticotropin-Releasing HormoneStress, PsychologicalSubstance-Related DisordersConceptsMajor depressive episodeAdverse childhood experiencesRisk of depressionTAT haplotypeAlcohol dependenceDepressive episodeLifetime riskAA womenCorticotropin-releasing hormone type 1 receptorOdds of MDERisk of MDELifetime substance use disorderType 1 receptorSubstance use disordersAfrican AmericansAfrican American womenChildhood experiencesDepression riskThree-SNP haplotypeAD riskUse disordersAdult depressionAlcohol consumptionCRHR1 haplotypeCRHR1