2023
Does 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 studies
2022
Alcohol 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 ResearchAlcohol 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 odds
2019
Alcohol-responsive genes identified in human iPSC-derived neural cultures
Jensen KP, Lieberman R, Kranzler HR, Gelernter J, Clinton K, Covault J. Alcohol-responsive genes identified in human iPSC-derived neural cultures. Translational Psychiatry 2019, 9: 96. PMID: 30862775, PMCID: PMC6414668, DOI: 10.1038/s41398-019-0426-5.Peer-Reviewed Original ResearchConceptsAlcohol-responsive genesGene expressionGene regulatory effectsTotal RNA sequencingCo-expressed genesNeural cell culturesCholesterol biosynthesis pathwayPrimary neural tissueCorrelation network analysisHuman-induced pluripotent stem cellsPluripotent stem cellsBiosynthesis pathwayCell culturesResponsive genesRNA sequencingNotch signalingEnrichment analysisMolecular mechanismsCell cycleAlcohol exposureGenesCell culture modelGenetic effectsCholesterol homeostasisStem cells
2018
GWAS and network analysis of co‐occurring nicotine and alcohol dependence identifies significantly associated alleles and network
Xiang B, Yang B, Zhou H, Kranzler H, Gelernter J. GWAS and network analysis of co‐occurring nicotine and alcohol dependence identifies significantly associated alleles and network. American Journal Of Medical Genetics Part B Neuropsychiatric Genetics 2018, 180: 3-11. PMID: 30488612, PMCID: PMC6918694, DOI: 10.1002/ajmg.b.32692.Peer-Reviewed Original ResearchMeSH KeywordsAdultAlcoholismAllelesBlack or African AmericanComorbidityEthanolFemaleG(M2) Activator ProteinGene FrequencyGene Regulatory NetworksGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMaleMiddle AgedNicotinePolymorphism, Single NucleotideProtein Interaction MapsRisk FactorsTobacco Use DisorderWhite PeopleConceptsGene subnetworksProtein-protein interaction (PPI) network analysisGenome-wide significant variantsInteraction network analysisGene-set analysisFunctional enrichment analysisSignificant SNPsQuantitative lociNerve growth factor pathwayGene enrichmentEnrichment analysisNetwork analysisGenetic traitsGrowth factor pathwaysRisk genesSignificant variantsGenesStudy of AddictionSNPsFactor pathwayGM2AAmphetamine addictionGenetic riskGWASSubnetworks
2017
GRIK1 and GABRA2 Variants Have Distinct Effects on the Dose‐Related Subjective Response to Intravenous Alcohol in Healthy Social Drinkers
Yang B, Arias AJ, Feinn R, Krystal JH, Gelernter J, Petrakis IL. GRIK1 and GABRA2 Variants Have Distinct Effects on the Dose‐Related Subjective Response to Intravenous Alcohol in Healthy Social Drinkers. Alcohol Clinical And Experimental Research 2017, 41: 2025-2032. PMID: 29131352, PMCID: PMC5764175, DOI: 10.1111/acer.13516.Peer-Reviewed Original ResearchGenomewide 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 sensitivityKLF12
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 metabolismNeurons
2014
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
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 releaseDifferentially co-expressed genes in postmortem prefrontal cortex of individuals with alcohol use disorders: influence on alcohol metabolism-related pathways
Zhang H, Wang F, Xu H, Liu Y, Liu J, Zhao H, Gelernter J. Differentially co-expressed genes in postmortem prefrontal cortex of individuals with alcohol use disorders: influence on alcohol metabolism-related pathways. Human Genetics 2014, 133: 1383-1394. PMID: 25073604, PMCID: PMC4185230, DOI: 10.1007/s00439-014-1473-x.Peer-Reviewed Original ResearchConceptsCo-expressed genesGenome-wide association studiesHumanHT-12 v4 Expression BeadChipGene modulesPostmortem prefrontal cortexGene co-expression network analysisCo-expression network analysisDAVID Bioinformatics ResourcesGene expression alterationsMetabolism-related pathwaysV4 Expression BeadChipCellular functionsTranscriptome profilesFatty acid metabolismBioinformatics resourcesEnrichment analysisExpression probesBiological pathwaysAssociation studiesAldehyde detoxificationExpression alterationsGenesMitochondrial functionBrain reward regionsAcid metabolism
2004
Altered NMDA Glutamate Receptor Antagonist Response in Individuals With a Family Vulnerability to Alcoholism
Petrakis IL, Limoncelli D, Gueorguieva R, Jatlow P, Boutros NN, Trevisan L, Gelernter J, Krystal JH. Altered NMDA Glutamate Receptor Antagonist Response in Individuals With a Family Vulnerability to Alcoholism. American Journal Of Psychiatry 2004, 161: 1776-1782. PMID: 15465973, DOI: 10.1176/ajp.161.10.1776.Peer-Reviewed Original ResearchAdultAffectAlcohol DrinkingAlcoholic IntoxicationAlcoholismBrief Psychiatric Rating ScaleDissociative DisordersDouble-Blind MethodEthanolFamilyFemaleGenetic Predisposition to DiseaseHumansInfusions, IntravenousKetamineMalePedigreePlacebosPsychoses, AlcoholicReceptors, N-Methyl-D-AspartateRisk Factors