Featured Publications
Genetics of substance use disorders in the era of big data
Gelernter J, Polimanti R. Genetics of substance use disorders in the era of big data. Nature Reviews Genetics 2021, 22: 712-729. PMID: 34211176, PMCID: PMC9210391, DOI: 10.1038/s41576-021-00377-1.Peer-Reviewed Original Research
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 riskGWASSubnetworksBiochemical, demographic, and self-reported tobacco-related predictors of the acute heart rate response to nicotine in smokers
Jensen KP, Valentine G, Buta E, DeVito EE, Gelernter J, Sofuoglu M. Biochemical, demographic, and self-reported tobacco-related predictors of the acute heart rate response to nicotine in smokers. Pharmacology Biochemistry And Behavior 2018, 173: 36-43. PMID: 30107183, PMCID: PMC6125200, DOI: 10.1016/j.pbb.2018.08.004.Peer-Reviewed Original ResearchConceptsAcute heart rate responseHeart rate responseNicotine infusionHigher nicotine metabolite ratioTobacco harm reduction approachesRate responseGreater withdrawal symptomsNicotine metabolite ratioBlood-based biomarkersNicotine delivery systemsWarrants further investigationHarm reduction approachWithdrawal symptomsCardiovascular functionLower nicotine levelsTobacco useMetabolite ratiosNicotine levelsSmokeless productsHigher cortisolSmokersHR effectsStimulatory effectNicotineDemographic characteristics
2017
Alcohol and nicotine codependence-associated DNA methylation changes in promoter regions of addiction-related genes
Xu H, Wang F, Kranzler HR, Gelernter J, Zhang H. Alcohol and nicotine codependence-associated DNA methylation changes in promoter regions of addiction-related genes. Scientific Reports 2017, 7: 41816. PMID: 28165486, PMCID: PMC5292964, DOI: 10.1038/srep41816.Peer-Reviewed Original Research
2016
A protocadherin gene cluster regulatory variant is associated with nicotine withdrawal and the urge to smoke
Jensen KP, Smith AH, Herman AI, Farrer LA, Kranzler HR, Sofuoglu M, Gelernter J. A protocadherin gene cluster regulatory variant is associated with nicotine withdrawal and the urge to smoke. Molecular Psychiatry 2016, 22: 242-249. PMID: 27067016, PMCID: PMC5390815, DOI: 10.1038/mp.2016.43.Peer-Reviewed Original ResearchMeSH KeywordsAdultBlack or African AmericanCadherinsDiagnostic and Statistical Manual of Mental DisordersFemaleGene Expression RegulationGenome-Wide Association StudyHumansMaleMultigene FamilyNicotinePolymorphism, Single NucleotideProtocadherinsRecurrenceSmokingSmoking CessationSubstance Withdrawal SyndromeTobacco Use DisorderWhite PeopleConceptsNicotine withdrawalSingle nucleotide polymorphismsNovel smoking cessation treatmentsAfrican AmericansSmoking cessation treatmentNicotine withdrawal symptomsOvernight smoking abstinenceEuropean American smokersFrontal cortex tissueΓ geneCessation treatmentTobacco smokingSmoking abstinenceWithdrawal symptomsAbstinent smokersAmerican smokersΓ gene expressionNicotine infusionSmoking urgesInfusion studiesSmokersMRNA expressionRisk allelesCortex tissueBrief questionnaire
2015
A CHRNA5 Smoking Risk Variant Decreases the Aversive Effects of Nicotine in Humans
Jensen KP, DeVito EE, Herman AI, Valentine GW, Gelernter J, Sofuoglu M. A CHRNA5 Smoking Risk Variant Decreases the Aversive Effects of Nicotine in Humans. Neuropsychopharmacology 2015, 40: 2813-2821. PMID: 25948103, PMCID: PMC4864657, DOI: 10.1038/npp.2015.131.Peer-Reviewed Original ResearchMeSH KeywordsAdultBlood PressureCognition DisordersCotinineFemaleGenome-Wide Association StudyHeart RateHumansMaleMiddle AgedNerve Tissue ProteinsNeuropsychological TestsNicotineNicotinic AgonistsPolymorphism, Single NucleotideReceptors, NicotinicSmokingSubstance Withdrawal SyndromeSurveys and QuestionnairesConceptsAversive effectsHeavy smokingRisk allelesSmoking-related disordersAfrican American smokersCHRNA5-CHRNA3Doses of nicotineHigh nicotine doseNicotine administrationIntravenous doseNicotine effectsNicotine doseAmerican smokersWithdrawal severityOvernight abstinenceAcute responseAA subjectsCardiovascular reactivityCHRNB4 gene clusterNicotineEuropean AmericansAversive responsesAdministration sessionsSmokingCognitive performance
2014
FKBP5 variation is associated with the acute and chronic effects of nicotine
Jensen KP, Herman AI, Morean ME, Kranzler HR, Gelernter J, Sofuoglu M. FKBP5 variation is associated with the acute and chronic effects of nicotine. The Pharmacogenomics Journal 2014, 15: 340-346. PMID: 25532758, PMCID: PMC4599366, DOI: 10.1038/tpj.2014.76.Peer-Reviewed Original ResearchMeSH KeywordsAllelesBlack or African AmericanBlood PressureDiagnostic and Statistical Manual of Mental DisordersGene FrequencyGenotypeHeart RateHumansHydrocortisoneInjections, IntravenousNicotineNicotinic AgonistsRNARNA, MessengerSmokingSubstance Withdrawal SyndromeTacrolimus Binding ProteinsWhite PeopleConceptsNicotine withdrawalFKBP5 mRNA expressionNegative drug effectsHeart rateIndependent cohortDrug effectsMRNA expressionMinor alleleChronic behavioral effectsEffects of nicotineStress hormone regulationLower cortisol levelsWarrants further investigationSevere nicotine withdrawalCurrent smokersBlood pressureHeavy smokersQuit attemptsHR responseSmoking behaviorCortisol responseCortisol levelsLower subjective ratingsSmokersChronic effectsRare Human Nicotinic Acetylcholine Receptor α4 Subunit (CHRNA4) Variants Affect Expression and Function of High-Affinity Nicotinic Acetylcholine Receptors
McClure-Begley TD, Papke RL, Stone KL, Stokes C, Levy AD, Gelernter J, Xie P, Lindstrom J, Picciotto MR. Rare Human Nicotinic Acetylcholine Receptor α4 Subunit (CHRNA4) Variants Affect Expression and Function of High-Affinity Nicotinic Acetylcholine Receptors. Journal Of Pharmacology And Experimental Therapeutics 2014, 348: 410-420. PMID: 24385388, PMCID: PMC3935145, DOI: 10.1124/jpet.113.209767.Peer-Reviewed Original ResearchConceptsNicotinic acetylcholine receptorsRare variantsSingle amino acid substitutionLaevis oocytesAmino acid substitutionsΑ4β2 nAChRsAcetylcholine receptorsIntracellular interactomesHEK-293 cellsX. laevis oocytesProteomic analysisGenetic variationHuman α4β2 nAChRsXenopus laevis oocytesVoltage-clamp electrophysiologyNeuronal nicotinic acetylcholine receptorsHigh-affinity nicotinic acetylcholine receptorsSubcellular distributionAcid substitutionsΑ4 nAChR subunitCohort of smokersEffects of nicotineNAChR subunitsCommon variantsΑ4 nAChR
2013
COMT Val158Met modulates subjective responses to intravenous nicotine and cognitive performance in abstinent smokers
Herman AI, Jatlow PI, Gelernter J, Listman JB, Sofuoglu M. COMT Val158Met modulates subjective responses to intravenous nicotine and cognitive performance in abstinent smokers. The Pharmacogenomics Journal 2013, 13: 490-497. PMID: 23459442, PMCID: PMC3675163, DOI: 10.1038/tpj.2013.1.Peer-Reviewed Original ResearchConceptsVal/Val genotypeAbstinent smokersVal genotypeGreater systolic blood pressureOvernight abstinent smokersVal158Met polymorphismSystolic blood pressureDoses of nicotineCatechol-O-methyltransferase (COMT) Val158Met polymorphismVal/ValEuropean American smokersNegative subjective effectsCOMT Val158Met polymorphismBlood pressureSmoking cessationAA smokersRisk factorsAmerican smokersIntravenous nicotineWithdrawal severityOvernight abstinenceSmokersNicotine addictionNicotine useSubjective effects
2012
Increased Genetic Vulnerability to Smoking at CHRNA5 in Early-Onset Smokers
Hartz SM, Short SE, Saccone NL, Culverhouse R, Chen L, Schwantes-An TH, Coon H, Han Y, Stephens SH, Sun J, Chen X, Ducci F, Dueker N, Franceschini N, Frank J, Geller F, Gubjartsson D, Hansel NN, Jiang C, Keskitalo-Vuokko K, Liu Z, Lyytikäinen LP, Michel M, Rawal R, Rosenberger A, Scheet P, Shaffer JR, Teumer A, Thompson JR, Vink JM, Vogelzangs N, Wenzlaff AS, Wheeler W, Xiao X, Yang BZ, Aggen SH, Balmforth AJ, Baumeister SE, Beaty T, Bennett S, Bergen AW, Boyd HA, Broms U, Campbell H, Chatterjee N, Chen J, Cheng YC, Cichon S, Couper D, Cucca F, Dick DM, Foroud T, Furberg H, Giegling I, Gu F, Hall AS, Hällfors J, Han S, Hartmann AM, Hayward C, Heikkilä K, Hewitt JK, Hottenga JJ, Jensen MK, Jousilahti P, Kaakinen M, Kittner SJ, Konte B, Korhonen T, Landi MT, Laatikainen T, Leppert M, Levy SM, Mathias RA, McNeil DW, Medland SE, Montgomery GW, Muley T, Murray T, Nauck M, North K, Pergadia M, Polasek O, Ramos EM, Ripatti S, Risch A, Ruczinski I, Rudan I, Salomaa V, Schlessinger D, Styrkársdóttir U, Terracciano A, Uda M, Willemsen G, Wu X, Abecasis G, Barnes K, Bickeböller H, Boerwinkle E, Boomsma DI, Caporaso N, Duan J, Edenberg HJ, Francks C, Gejman PV, Gelernter J, Grabe HJ, Hops H, Jarvelin MR, Viikari J, Kähönen M, Kendler KS, Lehtimäki T, Levinson DF, Marazita ML, Marchini J, Melbye M, Mitchell BD, Murray JC, Nöthen MM, Penninx BW, Raitakari O, Rietschel M, Rujescu D, Samani NJ, Sanders AR, Schwartz AG, Shete S, Shi J, Spitz M, Stefansson K, Swan GE, Thorgeirsson T, Völzke H, Wei Q, Wichmann H, Amos CI, Breslau N, Cannon DS, Ehringer M, Grucza R, Hatsukami D, Heath A, Johnson EO, Kaprio J, Madden P, Martin NG, Stevens VL, Stitzel JA, Weiss RB, Kraft P, Bierut LJ. Increased Genetic Vulnerability to Smoking at CHRNA5 in Early-Onset Smokers. JAMA Psychiatry 2012, 69: 854-860. PMID: 22868939, PMCID: PMC3482121, DOI: 10.1001/archgenpsychiatry.2012.124.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdolescent DevelopmentAdultAge of OnsetEuropeFemaleGene-Environment InteractionGenetic Association StudiesGenetic Predisposition to DiseaseHumansMaleNerve Tissue ProteinsNicotinePolymorphism, Single NucleotideReceptors, NicotinicSeverity of Illness IndexSmokingTobacco Use DisorderConceptsEarly-onset smokersLate-onset smokersHeavy smokersRisk allelesGenetic vulnerabilityRs16969968 genotypeLight smokersLight smokingRegular smokingSmokersSmokingMeta-AnalysisLogistic regressionRs16969968Single nucleotide polymorphismsAgeNonsynonymous single nucleotide polymorphismsCHRNA5Recent studiesAvailable genetic studiesAssociationSample sizeStudyCigarettesGenetic studies
2011
ACSL6 Is Associated with the Number of Cigarettes Smoked and Its Expression Is Altered by Chronic Nicotine Exposure
Chen J, Brunzell DH, Jackson K, van der Vaart A, Z. J, Payne TJ, Sherva R, Farrer LA, Gejman P, Levinson DF, Holmans P, Aggen SH, Damaj I, Kuo PH, Webb BT, Anton R, Kranzler HR, Gelernter J, Li MD, Kendler KS, Chen X. ACSL6 Is Associated with the Number of Cigarettes Smoked and Its Expression Is Altered by Chronic Nicotine Exposure. PLOS ONE 2011, 6: e28790. PMID: 22205969, PMCID: PMC3243669, DOI: 10.1371/journal.pone.0028790.Peer-Reviewed Original ResearchConceptsACSL6 geneNicotine exposureNicotinic receptor antagonist mecamylaminePrevious schizophrenia studiesChronic nicotine exposureNicotinic receptor activationHippocampus of miceNumber of cigarettesOsmotic mini pumpsQuantity of cigarettesNon-schizophrenic subjectsAssociation of schizophreniaCigarettes SmokedHeavy smokersTobacco smokingNicotine administrationAntagonist mecamylamineControl subjectsIndependent associationTobacco dependenceFTND scoreHigh riskMini pumpsChronic exposureReceptor activation
2006
C957T polymorphism of the dopamine D2 receptor gene modulates the effect of nicotine on working memory performance and cortical processing efficiency
Jacobsen LK, Pugh KR, Mencl WE, Gelernter J. C957T polymorphism of the dopamine D2 receptor gene modulates the effect of nicotine on working memory performance and cortical processing efficiency. Psychopharmacology 2006, 188: 530-540. PMID: 16896957, DOI: 10.1007/s00213-006-0469-1.Peer-Reviewed Original ResearchConceptsMemory performanceEffects of nicotineBrain regionsBrain functionFunctional magnetic resonanceCortical processing efficiencyRange of behavioralC957T polymorphismProcessing efficiencyPhonological rehearsalMemory taskMemory loadBrain responsesPerformance accuracyC957TMemoryBehavioral effectsNicotine administrationDopamine D2 receptor geneConclusionsThese findingsTobacco dependenceIndividual variationIndividual responsesTaskPlacebo patch