Featured Publications
Genome-wide meta-analysis of problematic alcohol use in 435,563 individuals yields insights into biology and relationships with other traits
Zhou H, Sealock JM, Sanchez-Roige S, Clarke TK, Levey DF, Cheng Z, Li B, Polimanti R, Kember RL, Smith RV, Thygesen JH, Morgan MY, Atkinson SR, Thursz MR, Nyegaard M, Mattheisen M, Børglum AD, Johnson EC, Justice AC, Palmer AA, McQuillin A, Davis LK, Edenberg HJ, Agrawal A, Kranzler HR, Gelernter J. Genome-wide meta-analysis of problematic alcohol use in 435,563 individuals yields insights into biology and relationships with other traits. Nature Neuroscience 2020, 23: 809-818. PMID: 32451486, PMCID: PMC7485556, DOI: 10.1038/s41593-020-0643-5.Peer-Reviewed Original ResearchConceptsRegulatory genomic regionsGenome-wide association studiesNovel risk lociEuropean ancestry individualsPolygenic risk score analysisIndependent risk variantsGenetic architectureGenomic regionsRisk lociAssociation studiesGenetic relationshipsRisk genesGenetic correlationsPsychiatric traitsRisk variantsRisk score analysisTraitsGenetic heritabilityYields insightsBiobank samplesMendelian randomizationGenesLociBiologyHeritabilityGenome-wide association study of alcohol consumption and use disorder in 274,424 individuals from multiple populations
Kranzler HR, Zhou H, Kember RL, Vickers Smith R, 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. Genome-wide association study of alcohol consumption and use disorder in 274,424 individuals from multiple populations. Nature Communications 2019, 10: 1499. PMID: 30940813, PMCID: PMC6445072, DOI: 10.1038/s41467-019-09480-8.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesAssociation studiesMillion Veteran Program sampleGenetic correlationsWide significant lociSignificant genetic correlationsPolygenic risk scoresCell type groupSignificant lociHeritable traitEnrichment analysisTraitsMultiple populationsLociPhenotypeProgram samples
2024
A 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 ResearchGenetic Underpinnings of the Transition From Alcohol Consumption to Alcohol Use Disorder: Shared and Unique Genetic Architectures in a Cross-Ancestry Sample
Kember R, Vickers-Smith R, Zhou H, Xu H, Jennings M, Dao C, Davis L, Sanchez-Roige S, Justice A, Gelernter J, Vujkovic M, Kranzler H. Genetic Underpinnings of the Transition From Alcohol Consumption to Alcohol Use Disorder: Shared and Unique Genetic Architectures in a Cross-Ancestry Sample. American Journal Of Psychiatry 2023, 180: 584-593. PMID: 37282553, PMCID: PMC10731616, DOI: 10.1176/appi.ajp.21090892.Peer-Reviewed Original ResearchDoes polygenic risk for substance‐related traits predict ages of onset and progression of symptoms?
Kranzler H, Feinn R, Xu H, Ho B, Saini D, Nicastro O, Jacoby A, Toikumo S, Gelernter J, Hartwell E, Kember R. Does polygenic risk for substance‐related traits predict ages of onset and progression of symptoms? Addiction 2023, 118: 1675-1686. PMID: 37069489, PMCID: PMC10525011, DOI: 10.1111/add.16210.Peer-Reviewed Original ResearchConceptsOpioid use disorderSubstance use disordersProgression of symptomsPolygenic risk scoresAlcohol use disorderUse disordersAfrican ancestry individualsGenetic riskRegular useEuropean ancestry individualsEarly onsetMore rapid progressionRegular alcohol useShorter progression timeAge of onsetFirst substance useDiscovery sampleUS inpatientsOnset of problemsOutpatient settingDisease progressionRapid progressionSymptom progressionRisk scoreGenome-wide association studiesMulti-trait genome-wide association analyses leveraging alcohol use disorder findings identify novel loci for smoking behaviors in the Million Veteran Program
Cheng Y, Dao C, Zhou H, Li B, Kember R, Toikumo S, Zhao H, Gelernter J, Kranzler H, Justice A, Xu K. Multi-trait genome-wide association analyses leveraging alcohol use disorder findings identify novel loci for smoking behaviors in the Million Veteran Program. Translational Psychiatry 2023, 13: 148. PMID: 37147289, PMCID: PMC10162964, DOI: 10.1038/s41398-023-02409-2.Peer-Reviewed Original ResearchConceptsSingle-trait genome-wide association studiesGenome-wide association studiesNovel lociPower of GWASJoint genome-wide association studyGenome-wide significant lociMillion Veteran ProgramGenome-wide associationSubstance use traitsGWAS summary statisticsNovel genetic variantsMulti-trait analysisFunctional annotationUse traitsSignificant lociHeritable traitMultiple lociAssociation studiesColocalization analysisLociPleiotropic effectsMTAgVeteran ProgramGenetic variantsTraitsPolygenic risk score for problematic alcohol use predicts heavy drinking and alcohol use disorder symptoms in young adulthood after accounting for adolescent alcohol use and parental alcohol use disorder
Wang F, Hicks B, Zhou H, Kranzler H, Gelernter J, Zucker R. Polygenic risk score for problematic alcohol use predicts heavy drinking and alcohol use disorder symptoms in young adulthood after accounting for adolescent alcohol use and parental alcohol use disorder. Drug And Alcohol Dependence 2023, 248: 109909. PMID: 37163864, PMCID: PMC11013565, DOI: 10.1016/j.drugalcdep.2023.109909.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 ResearchMeSH KeywordsAlcohol DrinkingAlcoholismHumansLongitudinal StudiesStress Disorders, Post-TraumaticVeteransConceptsAlcohol 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
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 ResearchMeSH KeywordsAgedAlcohol DrinkingAlcoholismFemaleGenome-Wide Association StudyHumansMaleVeteransWhite PeopleConceptsGenome-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 regressionTraitsPhenome-wide Association Analysis of Substance Use Disorders in a Deeply Phenotyped Sample
Kember RL, Hartwell EE, Xu H, Rotenberg J, Almasy L, Zhou H, Gelernter J, Kranzler HR. Phenome-wide Association Analysis of Substance Use Disorders in a Deeply Phenotyped Sample. Biological Psychiatry 2022, 93: 536-545. PMID: 36273948, PMCID: PMC9931661, DOI: 10.1016/j.biopsych.2022.08.010.Peer-Reviewed Original ResearchConceptsSubstance use disordersAlcohol use disorderOpioid use disorderPolygenic risk scoresUse disordersCo-occurring psychiatric disordersComprehensive psychiatric interviewSemi-Structured AssessmentElectronic health recordsControl subjectsLow prevalencePsychiatric interviewRisk scorePsychiatric disordersPhenome-wide association analysisDrug dependenceEuropean individualsHealth recordsLifetime cannabisPhenome-wide association studyDisordersAfrican ancestry individualsDSM diagnosesPopulation sampleGenetic liabilityAlcohol consumption and telomere length: Mendelian randomization clarifies alcohol’s effects
Topiwala A, Taschler B, Ebmeier KP, Smith S, Zhou H, Levey DF, Codd V, Samani NJ, Gelernter J, Nichols TE, Burgess S. Alcohol consumption and telomere length: Mendelian randomization clarifies alcohol’s effects. Molecular Psychiatry 2022, 27: 4001-4008. PMID: 35879401, PMCID: PMC9718662, DOI: 10.1038/s41380-022-01690-9.Peer-Reviewed Original ResearchAssociations 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 functionAlcohol withdrawal in past‐year drinkers with unhealthy alcohol use: Prevalence, characteristics, and correlates in a national epidemiologic survey
Livne O, Feinn R, Knox J, Hartwell EE, Gelernter J, Hasin DS, Kranzler HR. Alcohol withdrawal in past‐year drinkers with unhealthy alcohol use: Prevalence, characteristics, and correlates in a national epidemiologic survey. Alcohol Clinical And Experimental Research 2022, 46: 422-433. PMID: 35275407, PMCID: PMC8928097, DOI: 10.1111/acer.14781.Peer-Reviewed Original ResearchConceptsAlcohol withdrawal syndromeUnhealthy alcohol useSerious adverse outcomesNational Epidemiologic SurveyAlcohol useHealthcare utilizationAdverse outcomesGeneral populationPsychiatric disordersEpidemiologic SurveyAlcohol Use Disorders Identification Test-Consumption (AUDIT-C) questionnairePast-year alcohol use disorderNausea/vomitingMajor depressive disorderImportant clinical populationAlcohol use disorderRelated Conditions-IIIBorderline personality disorderPast-year prevalenceAlcohol withdrawalWithdrawal syndromeWithdrawal symptomsDepressive disorderUnhealthy drinkersHigher oddsGenome-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 ResearchMeSH KeywordsAlcohol DrinkingAlcoholismDouble-Blind MethodFemaleFructoseHumansMaleMiddle AgedReceptors, Kainic AcidTopiramateConceptsAlcohol 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
2021
Drinking and smoking polygenic risk is associated with childhood and early-adulthood psychiatric and behavioral traits independently of substance use and psychiatric genetic risk
De Angelis F, Wendt FR, Pathak GA, Tylee DS, Goswami A, Gelernter J, Polimanti R. Drinking and smoking polygenic risk is associated with childhood and early-adulthood psychiatric and behavioral traits independently of substance use and psychiatric genetic risk. Translational Psychiatry 2021, 11: 586. PMID: 34775470, PMCID: PMC8590689, DOI: 10.1038/s41398-021-01713-z.Peer-Reviewed Original ResearchMeSH KeywordsAdultAlcohol DrinkingChildHumansMultifactorial InheritanceRisk FactorsSmokingSubstance-Related DisordersTobacco SmokingYoung AdultConceptsSubstance useYoung adultsBehavioral traitsPhiladelphia Neurodevelopmental CohortRemoval of participantsAnxiety-related traitsRisk-taking behaviorVerbal reasoningCognitive performancePolygenic risk scoresSocial competenciesNeurobiological processesNeurodevelopmental CohortPsychiatric genetic riskDrinking behaviorParent educationPRS associationsPolygenic riskPsychopathologyGenetic overlapPsychotic symptomsAdverse health outcomesHazardous behaviorEducational attainmentTobacco smokingThe addiction risk factor: A unitary genetic vulnerability characterizes substance use disorders and their associations with common correlates
Hatoum AS, Johnson EC, Colbert SMC, Polimanti R, Zhou H, Walters RK, Gelernter J, Edenberg HJ, Bogdan R, Agrawal A. The addiction risk factor: A unitary genetic vulnerability characterizes substance use disorders and their associations with common correlates. Neuropsychopharmacology 2021, 47: 1739-1745. PMID: 34750568, PMCID: PMC9372072, DOI: 10.1038/s41386-021-01209-w.Peer-Reviewed Original ResearchCombined analysis of the moderating effect of a GRIK1 polymorphism on the effects of topiramate for treating alcohol use disorder
Kranzler HR, Hartwell EE, Feinn R, Pond T, Witkiewitz K, Gelernter J, Crist RC. Combined analysis of the moderating effect of a GRIK1 polymorphism on the effects of topiramate for treating alcohol use disorder. Drug And Alcohol Dependence 2021, 225: 108762. PMID: 34049101, PMCID: PMC8282735, DOI: 10.1016/j.drugalcdep.2021.108762.Peer-Reviewed Original Research
2019
Epigenome‐Wide DNA Methylation Association Analysis Identified Novel Loci in Peripheral Cells for Alcohol Consumption Among European American Male Veterans
Xu K, Montalvo‐Ortiz J, Zhang X, Southwick SM, Krystal JH, Pietrzak RH, Gelernter J. Epigenome‐Wide DNA Methylation Association Analysis Identified Novel Loci in Peripheral Cells for Alcohol Consumption Among European American Male Veterans. Alcohol Clinical And Experimental Research 2019, 43: 2111-2121. PMID: 31386212, PMCID: PMC9377208, DOI: 10.1111/acer.14168.Peer-Reviewed Original ResearchConceptsEpigenome-wide association studiesDNA methylationCpG sitesSignificant CpG sitesHigh-density methylation arraysNovel DNA methylation sitesNew CpG sitesDNA methylation sitesEpigenome-wide DNA methylationAmino acid transportIndividual CpG sitesGene lengthPeripheral cellsNovel lociDNA sitesKEGG databaseMethylation sitesEnrichment analysisMethylation arraysAssociation studiesAssociation analysisGenesMethylationAcid transportFalse discovery rate