Featured Publications
Genome-wide association study of post-traumatic stress disorder reexperiencing symptoms in >165,000 US veterans
Gelernter J, Sun N, Polimanti R, Pietrzak R, Levey DF, Bryois J, Lu Q, Hu Y, Li B, Radhakrishnan K, Aslan M, Cheung KH, Li Y, Rajeevan N, Sayward F, Harrington K, Chen Q, Cho K, Pyarajan S, Sullivan PF, Quaden R, Shi Y, Hunter-Zinck H, Gaziano JM, Concato J, Zhao H, Stein MB. Genome-wide association study of post-traumatic stress disorder reexperiencing symptoms in >165,000 US veterans. Nature Neuroscience 2019, 22: 1394-1401. PMID: 31358989, PMCID: PMC6953633, DOI: 10.1038/s41593-019-0447-7.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesAssociation studiesHigh linkage disequilibrium regionLinkage disequilibrium regionWide association studyDisequilibrium regionBioinformatics analysisTranscriptomic profilesMillion Veteran ProgramChromosome 17Genetic risk factorsNew insightsUK Biobank dataReexperiencing of traumaStriatal medium spiny neuronsVeteran ProgramSignificant regionsCAMKVEuropean AmericansBiobank dataMedium spiny neuronsTCF4BiologyKANSL1African American cohort
2024
Genome-wide association study of the common retinal disorder epiretinal membrane: Significant risk loci in each of three American populations
Gelernter J, Levey D, Galimberti M, Harrington K, Zhou H, Adhikari K, Gupta P, Program V, Gaziano J, Eliott D, Stein M. Genome-wide association study of the common retinal disorder epiretinal membrane: Significant risk loci in each of three American populations. Cell Genomics 2024, 4: 100582. PMID: 38870908, PMCID: PMC11228954, DOI: 10.1016/j.xgen.2024.100582.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesMillion Veteran ProgramRisk lociAssociation studiesTrans-ancestry meta-analysisSignificant risk lociPathway enrichment analysisEpiretinal membraneTrans-ancestryGenome-wideMultiple traitsGenetic associationEnrichment analysisGene expressionEuropean AmericansLoss of visual acuityVeteran ProgramGenetic correlationsLociBiological mechanismsAmerican populationVisual acuityRetinal conditionsControl individualsRetinal surface
2023
Baseline platelet serotonin in a multi-site treatment study of depression in veterans administration patients: Distribution and effects of demographic variables and serotonin reuptake inhibitors
Anderson G, Ramsey C, Lynch K, Gelernter J, Oslin D. Baseline platelet serotonin in a multi-site treatment study of depression in veterans administration patients: Distribution and effects of demographic variables and serotonin reuptake inhibitors. Journal Of Affective Disorders 2023, 327: 368-377. PMID: 36754092, DOI: 10.1016/j.jad.2023.02.017.Peer-Reviewed Original ResearchConceptsReuptake inhibitorsVeterans Administration patientsTreatment studiesSubset of patientsNorepinephrine reuptake inhibitorsCross-sectional studyEffect of ageDose adjustmentAfrican American individualsDemographic variablesMean plateletDrug exposurePlatelet serotoninSerotonin valuesPatientsClinical implicationsHealth recordsMale groupSSRIsDepressionPlateletsEuropean AmericansInhibitorsSex differencesGroup means
2020
Genome-wide association study of smoking trajectory and meta-analysis of smoking status in 842,000 individuals
Xu K, Li B, McGinnis KA, Vickers-Smith R, Dao C, Sun N, Kember RL, Zhou H, Becker WC, Gelernter J, Kranzler HR, Zhao H, Justice AC. Genome-wide association study of smoking trajectory and meta-analysis of smoking status in 842,000 individuals. Nature Communications 2020, 11: 5302. PMID: 33082346, PMCID: PMC7598939, DOI: 10.1038/s41467-020-18489-3.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesLarge genome-wide association studiesMillion Veteran ProgramAssociation studiesExpression quantitative trait lociQuantitative trait lociChromatin interactionsComplex traitsFunctional annotationTrait lociSequencing ConsortiumDozen genesSignificant lociSmoking phenotypesLociMultiple populationsNew insightsPhenotypeVeteran ProgramGenetic vulnerabilityGenesTraitsAnnotationEuropean AmericansConsortium
2019
Genome‐wide scan identifies opioid overdose risk locus close to MCOLN1
Cheng Z, Yang B, Zhou H, Nunez Y, Kranzler HR, Gelernter J. Genome‐wide scan identifies opioid overdose risk locus close to MCOLN1. Addiction Biology 2019, 25: e12811. PMID: 31362332, PMCID: PMC7485539, DOI: 10.1111/adb.12811.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesMucolipin-1Expression profilesGenome-wide significant signalsAssociation studiesPost-GWAS analysisWide association studyDrug repositioning analysisCation channel activityFunctional categoriesConnectivity Map databaseDrug targetsRisk genesGenesChannel activityPatatin-like phospholipaseNetwork analysisPNPLA6Significant signalEuropean Americans
2018
Translational studies support a role for serotonin 2B receptor (HTR2B) gene in aggression-related cannabis response
Montalvo-Ortiz JL, Zhou H, D’Andrea I, Maroteaux L, Lori A, Smith A, Ressler KJ, Nuñez YZ, Farrer LA, Zhao H, Kranzler HR, Gelernter J. Translational studies support a role for serotonin 2B receptor (HTR2B) gene in aggression-related cannabis response. Molecular Psychiatry 2018, 23: 2277-2286. PMID: 29875475, PMCID: PMC6281782, DOI: 10.1038/s41380-018-0077-6.Peer-Reviewed Original ResearchConceptsGrady Trauma ProjectAfrican AmericansWild-type miceReceptor geneEffects of cannabisWide significant risk lociResident-intruder paradigmImpulsivity/aggressionConcordant findingsTHC administrationKnockout miceTranslational studiesAA subjectsCannabis useStudy designTrauma ProjectAdverse effectsMiceCannabisAggressive behaviorEuropean AmericansNominal associationAdverse consequencesGenome-wide association study (GWAS) designRisk loci
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
2013
Genome-wide Association Study Identifies New Susceptibility Loci for Posttraumatic Stress Disorder
Xie P, Kranzler HR, Yang C, Zhao H, Farrer LA, Gelernter J. Genome-wide Association Study Identifies New Susceptibility Loci for Posttraumatic Stress Disorder. Biological Psychiatry 2013, 74: 656-663. PMID: 23726511, PMCID: PMC3810148, DOI: 10.1016/j.biopsych.2013.04.013.Peer-Reviewed Original ResearchConceptsSingle nucleotide polymorphismsGenome-wide significanceFirst intronGenome-wide association study analysisGenome-wide association analysisNew susceptibility lociCandidate gene association studiesNew susceptibility genesCommon risk allelesGene association studiesChromosome 7p12Association studiesAssociation analysisSusceptibility lociSusceptibility genesGenetic variantsNucleotide polymorphismsIntronsTLL1GenesLociRisk allelesGenetic factorsSignificant signalEuropean Americans
2012
Identification of POMC Exonic Variants Associated with Substance Dependence and Body Mass Index
Wang F, Gelernter J, Kranzler HR, Zhang H. Identification of POMC Exonic Variants Associated with Substance Dependence and Body Mass Index. PLOS ONE 2012, 7: e45300. PMID: 23028917, PMCID: PMC3444488, DOI: 10.1371/journal.pone.0045300.Peer-Reviewed Original ResearchConceptsBody mass indexSubstance dependenceMass indexExact testRare variantsAfrican AmericansNormal weight groupCommon variantsFisher's exact testProopiomelanocortin geneObese groupObese subjectsExonic variantsMelanocortin peptidesEuropean AmericansLogistic regressionCommon polymorphismsOverweightRare exonic variantsVariants AssociatedPopulation-specific mannerRiskAssociationObesityGroupHypermethylation of OPRM1 promoter region in European Americans with alcohol dependence
Zhang H, Herman AI, Kranzler HR, Anton RF, Simen AA, Gelernter J. Hypermethylation of OPRM1 promoter region in European Americans with alcohol dependence. Journal Of Human Genetics 2012, 57: 670-675. PMID: 22914673, PMCID: PMC3481015, DOI: 10.1038/jhg.2012.98.Peer-Reviewed Original ResearchMeSH KeywordsAdultAlcoholismCase-Control StudiesCocaine-Related DisordersComorbidityCpG IslandsDNA MethylationFemaleGenetic Predisposition to DiseaseGenetics, PopulationGenome, HumanHumansMaleMarijuana AbuseMiddle AgedMultivariate AnalysisPromoter Regions, GeneticReceptors, Opioid, muRisk FactorsSequence Analysis, DNAWhite PeopleConceptsChildhood adversityOPRM1 promoter regionAD casesΜ-opioid receptor geneSubstance dependence disordersΜ-opioid receptorDays of intoxicationEffects of alcoholEuropean American controlsPromoter methylation levelsPeripheral bloodMethylation levelsDependence disordersAlcohol dependenceMultivariate analysisPromoter regionPromoter hypermethylationReceptor geneIllicit drugsEuropean AmericansMultiple comparisonsBisulfite sequencing analysisOverall methylation levelsAmerican controlsSex
2011
Childhood Adversity Increases Risk for Nicotine Dependence and Interacts with α5 Nicotinic Acetylcholine Receptor Genotype Specifically in Males
Xie P, Kranzler HR, Zhang H, Oslin D, Anton RF, Farrer LA, Gelernter J. Childhood Adversity Increases Risk for Nicotine Dependence and Interacts with α5 Nicotinic Acetylcholine Receptor Genotype Specifically in Males. Neuropsychopharmacology 2011, 37: 669-676. PMID: 22012472, PMCID: PMC3260970, DOI: 10.1038/npp.2011.240.Peer-Reviewed Original ResearchConceptsChildhood adversityRs16969968 genotypeND riskSex differencesNicotinic acetylcholine receptor genesAcetylcholine receptor genesPotential sex differencesNicotine dependence riskFagerstrom TestNicotine intakeSmoking riskIncrease riskNicotine dependenceRodent modelsReceptor genotypeND scoresEarly life experiencesEuropean AmericansReceptor geneWomenRiskGene × environment effectsMen
2009
Cognitive Flexibility is Associated with KIBRA Variant and Modulated by Recent Tobacco Use
Zhang H, Kranzler HR, Poling J, Gruen JR, Gelernter J. Cognitive Flexibility is Associated with KIBRA Variant and Modulated by Recent Tobacco Use. Neuropsychopharmacology 2009, 34: 2508-2516. PMID: 19606085, PMCID: PMC2898508, DOI: 10.1038/npp.2009.80.Peer-Reviewed Original ResearchConceptsCognitive flexibilityPerseverative errorsPerseverative responsesWisconsin Card Sorting TestMemory performance measuresCard Sorting TestSorting TestRs17070145Main effectInteraction effectsEuropean AmericansRecencyPopulation-specific wayRecent tobacco usePerformance measuresTobacco useSynaptic plasticityModeratesKIBRAAfrican AmericansSmokersFlexibilityPopulation admixture modulates risk for alcohol dependence
Zuo L, Luo X, Listman JB, Kranzler HR, Wang S, Anton RF, Blumberg HP, Stein MB, Pearlson GD, Covault J, Charney DS, van Kammen DP, Price LH, Lappalainen J, Cramer J, Krystal JH, Gelernter J. Population admixture modulates risk for alcohol dependence. Human Genetics 2009, 125: 605-613. PMID: 19306106, PMCID: PMC2777998, DOI: 10.1007/s00439-009-0647-4.Peer-Reviewed Original Research
2007
Population-specific effects of the Asn40Asp polymorphism at the μ-opioid receptor gene (OPRM1) on HPA-axis activation
Hernandez-Avila CA, Covault J, Wand G, Zhang H, Gelernter J, Kranzler HR. Population-specific effects of the Asn40Asp polymorphism at the μ-opioid receptor gene (OPRM1) on HPA-axis activation. Pharmacogenetics And Genomics 2007, 17: 1031-1038. PMID: 18004207, DOI: 10.1097/fpc.0b013e3282f0b99c.Peer-Reviewed Original ResearchMeSH KeywordsAdrenocorticotropic HormoneAdultAllelesAmino Acid SubstitutionAsian PeopleDouble-Blind MethodFemaleGenetics, PopulationGenotypeHumansHydrocortisoneHypothalamo-Hypophyseal SystemMaleNaloxonePharmacogeneticsPituitary-Adrenal SystemPolymorphism, Single NucleotideReceptors, Opioid, muWhite PeopleConceptsHPA axis activationCortisol responseAsn40 homozygotesAsn40Asp polymorphismAsp40 alleleSingle nucleotide polymorphism A118GHPA axis responsePlacebo-controlled administrationΜ-opioid receptor geneGreater cortisol responseIntravenous naloxoneOpioid blockadeAxis activationAdrenocorticotropic hormoneA118GHealthy individualsOPRM1 SNPsNaloxoneCortisol concentrationsHormonal responsesEuropean AmericansObserved associationsHealthy participantsWhole bloodReceptor geneThe OPRD1 and OPRK1 loci in alcohol or drug dependence: OPRD1 variation modulates substance dependence risk
Zhang H, Kranzler HR, Yang BZ, Luo X, Gelernter J. The OPRD1 and OPRK1 loci in alcohol or drug dependence: OPRD1 variation modulates substance dependence risk. Molecular Psychiatry 2007, 13: 531-543. PMID: 17622222, PMCID: PMC3163084, DOI: 10.1038/sj.mp.4002035.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAlcoholismCase-Control StudiesCocaine-Related DisordersEuropeExonsFemaleGenetic Predisposition to DiseaseHaplotypesHeroin DependenceHumansLinkage DisequilibriumMaleMiddle AgedPolymorphism, Single NucleotideReceptors, Opioid, deltaReceptors, Opioid, kappaRiskSubstance-Related DisordersUnited StatesConceptsLogistic regression analysisSingle nucleotide polymorphismsRegression analysisTag single nucleotide polymorphismsOPRD1 variantsG alleleC alleleDrug dependenceSignificant associationRisk effectsEuropean AmericansStratification artifactSignificant differencesPositive associationHaplotypic associationsMultiple testingAssociationOPRK1OPRD1Dependence riskSD
2006
Genomewide Linkage Scan for Nicotine Dependence: Identification of a Chromosome 5 Risk Locus
Gelernter J, Panhuysen C, Weiss R, Brady K, Poling J, Krauthammer M, Farrer L, Kranzler HR. Genomewide Linkage Scan for Nicotine Dependence: Identification of a Chromosome 5 Risk Locus. Biological Psychiatry 2006, 61: 119-126. PMID: 17081504, DOI: 10.1016/j.biopsych.2006.08.023.Peer-Reviewed Original ResearchMeSH KeywordsChromosome MappingChromosomes, Human, Pair 5FemaleGene FrequencyGenetic LinkageGenetic Predisposition to DiseaseHumansLod ScoreMaleMixed Function OxygenasesMultienzyme ComplexesNuclear FamilyPedigreePhenotypePolymorphism, Single NucleotideReproducibility of ResultsRetrospective StudiesTobacco Use DisorderConceptsRisk lociLinkage scanGenomewide linkage scanSignificant single-nucleotide polymorphism associationsGenetic linkage analysisSingle nucleotide polymorphism associationsHighest LOD scoreLinkage peakChromosome 5Linkage signalChromosome 7Small nuclear familiesLinkage analysisPeptidylglycine alphaLociLOD scoreDistinct populationsMultiple individualsGenesEA subjectsPhysiological hypothesisPolymorphism associationAA partEuropean Americans
2005
Increased dopamine transporter availability associated with the 9-repeat allele of the SLC6A3 gene.
van Dyck CH, Malison RT, Jacobsen LK, Seibyl JP, Staley JK, Laruelle M, Baldwin RM, Innis RB, Gelernter J. Increased dopamine transporter availability associated with the 9-repeat allele of the SLC6A3 gene. Journal Of Nuclear Medicine 2005, 46: 745-51. PMID: 15872345.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAged, 80 and overAgingCocaineCorpus StriatumDopamine Plasma Membrane Transport ProteinsFemaleGene FrequencyGenetic TestingHumansMaleMembrane GlycoproteinsMembrane Transport ProteinsMicrosatellite RepeatsMiddle AgedNerve Tissue ProteinsPolymorphism, GeneticRadionuclide ImagingRadiopharmaceuticalsTissue DistributionConceptsStriatal DAT availabilityDAT availabilityDopamine transporterDAT genotypeDopamine transporter availabilityBrain uptakeTransporter availabilityHealthy European AmericansDAT levelsCarbomethoxy-3betaClinical phenotypeMean increaseNeuropsychiatric diseasesSLC6A3 polymorphismsVNTR polymorphismSLC6A3European AmericansSLC6A3 geneHomozygotesHuman clinical phenotypesSubregion analysisPolymorphismDivergent resultsAssociationCommon alleles
2001
Polymorphism of the 5-HT1B Receptor Gene (HTR1B): Strong Within-Locus Linkage Disequilibrium without Association to Antisocial Substance Dependence
Kranzler HR, Hernandez-Avila CA, Gelernter J. Polymorphism of the 5-HT1B Receptor Gene (HTR1B): Strong Within-Locus Linkage Disequilibrium without Association to Antisocial Substance Dependence. Neuropsychopharmacology 2001, 26: 115-122. PMID: 11751038, DOI: 10.1016/s0893-133x(01)00283-4.Peer-Reviewed Original ResearchConceptsSubstance dependenceAlcohol dependenceAntisocial personality disorderAntisocial alcoholismG861C polymorphismAntisocial diagnosisSouthwestern American IndiansAfrican AmericansAllelic associationSerotonergic abnormalitiesSerotonin receptorsFurther evaluationPersonality disorderLinkage disequilibriumReceptor geneDisordersPopulation groupsEuropean AmericansAssociationHTR1BDiagnosisAlcoholismPresent studyAmerican IndiansFunctional variants
2000
Family‐Based study of DRD2 alleles in alcohol and drug dependence
Blomqvist O, Gelernter J, Kranzler H. Family‐Based study of DRD2 alleles in alcohol and drug dependence. American Journal Of Medical Genetics 2000, 96: 659-664. PMID: 11054774, DOI: 10.1002/1096-8628(20001009)96:5<659::aid-ajmg12>3.0.co;2-g.Peer-Reviewed Original ResearchConceptsCase-control studyDrug dependenceAlcohol dependenceFamily-based studySubstance dependenceRecent family-based studyNumerous case-control studiesDSM-IV criteriaDopamine D2 receptor geneDRD2 allelesPresent studyD2 receptor geneDSM-IIIVariant allelesTransmission disequilibrium testConflicting resultsReceptor geneNegative resultsPositive associationEuropean AmericansTaqI AEuropean ancestryLinkage disequilibriumDisequilibrium testSmall nuclear families