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 lociGenome-wide Association Study Identifies a Regulatory Variant of RGMA Associated With Opioid Dependence in European Americans
Cheng Z, Zhou H, Sherva R, Farrer LA, Kranzler HR, Gelernter J. Genome-wide Association Study Identifies a Regulatory Variant of RGMA Associated With Opioid Dependence in European Americans. Biological Psychiatry 2018, 84: 762-770. PMID: 29478698, PMCID: PMC6041180, DOI: 10.1016/j.biopsych.2017.12.016.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesAssociation studiesHomologous mouse geneMouse geneAxon guidance proteinRegulatory variantsCoexpression analysisOpioid dependenceTranscript variantsGenetic studiesChromosome 15Guidance proteinsRNA expressionNominal significanceMessenger RNA expressionGenesRepulsive guidance molecule AHigh expressionRGMaRisk allelesChronic morphine injectionDSM-IV diagnosisExpressionNew leadsMorphine injection
2017
Genomewide 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
2016
The role of genes involved in stress, neural plasticity, and brain circuitry in depressive phenotypes: Convergent findings in a mouse model of neglect
Montalvo-Ortiz JL, Bordner KA, Carlyle BC, Gelernter J, Simen AA, Kaufman J. The role of genes involved in stress, neural plasticity, and brain circuitry in depressive phenotypes: Convergent findings in a mouse model of neglect. Behavioural Brain Research 2016, 315: 71-74. PMID: 27506655, PMCID: PMC5396458, DOI: 10.1016/j.bbr.2016.08.010.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDepressionDisease Models, AnimalGene Expression RegulationInhibitor of Differentiation ProteinsMaleMaternal DeprivationMaze LearningMiceMice, Inbred C57BLMice, Inbred DBAMicroarray AnalysisNerve Tissue ProteinsNeuronal PlasticityPrefrontal CortexReceptors, N-Methyl-D-AspartateRNA, MessengerStress, PsychologicalSwimmingConceptsTubulin Polymerization Promoting ProteinRole of genesGene expression dataEpigenetic changesGene expressionPhenotype dataExpression dataPrefrontal cortex tissueGenesSecondary analysisMedial prefrontal cortex (mPFC) tissueGlutamate NMDA receptorsAdult male miceId-3Early life stressPhenotypeSwimming testMale miceNMDA receptorsDepression riskMaternal separationMouse modelDepressive phenotypeBrain circuitryBehavioral differences
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 releaseGenetic risk prediction and neurobiological understanding of alcoholism
Levey DF, Le-Niculescu H, Frank J, Ayalew M, Jain N, Kirlin B, Learman R, Winiger E, Rodd Z, Shekhar A, Schork N, Kiefe F, Wodarz N, Müller-Myhsok B, Dahmen N, Nöthen M, Sherva R, Farrer L, Smith A, Kranzler H, Rietschel M, Gelernter J, Niculescu A. Genetic risk prediction and neurobiological understanding of alcoholism. Translational Psychiatry 2014, 4: e391-e391. PMID: 24844177, PMCID: PMC4035721, DOI: 10.1038/tp.2014.29.Peer-Reviewed Original ResearchConceptsTop candidate genesCandidate genesGenetic risk predictionGenome-wide association study dataFunctional genomics approachConvergent functional genomics approachAssociation study dataGene expression dataInitial discovery stepGenomic approachesKey genesSignal transductionSignificant genetic overlapTop genesRelevant genesBiological pathwaysExpression dataTop findingsGenesStrict Bonferroni correctionGenetic overlapProtein knockout miceSmall panelFatty acidsKnockout mice
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
2009
Twenty-one-base-pair insertion polymorphism creates an enhancer element and potentiates SLC6A1 GABA transporter promoter activity
Hirunsatit R, George ED, Lipska BK, Elwafi HM, Sander L, Yrigollen CM, Gelernter J, Grigorenko EL, Lappalainen J, Mane S, Nairn AC, Kleinman JE, Simen AA. Twenty-one-base-pair insertion polymorphism creates an enhancer element and potentiates SLC6A1 GABA transporter promoter activity. Pharmacogenetics And Genomics 2009, 19: 53-65. PMID: 19077666, PMCID: PMC2791799, DOI: 10.1097/fpc.0b013e328318b21a.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAnimalsBase SequenceBlack or African AmericanCase-Control StudiesCell LineDNA PrimersEnhancer Elements, GeneticFemaleGABA Plasma Membrane Transport ProteinsGene ExpressionHippocampusHumansMaleMiceMiddle AgedMinisatellite RepeatsMolecular Sequence DataMutagenesis, InsertionalPharmacogeneticsPolymorphism, GeneticPromoter Regions, GeneticRecombinant ProteinsRNA, MessengerSchizophreniaSequence Homology, Nucleic AcidTranscriptional ActivationYoung Adult
2008
Genetic Variants of Nogo-66 Receptor with Possible Association to Schizophrenia Block Myelin Inhibition of Axon Growth
Budel S, Padukkavidana T, Liu BP, Feng Z, Hu F, Johnson S, Lauren J, Park JH, McGee AW, Liao J, Stillman A, Kim JE, Yang BZ, Sodi S, Gelernter J, Zhao H, Hisama F, Arnsten AF, Strittmatter SM. Genetic Variants of Nogo-66 Receptor with Possible Association to Schizophrenia Block Myelin Inhibition of Axon Growth. Journal Of Neuroscience 2008, 28: 13161-13172. PMID: 19052207, PMCID: PMC2892845, DOI: 10.1523/jneurosci.3828-08.2008.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrainChick EmbryoChlorocebus aethiopsChromosome MappingCodonCOS CellsFemaleGenetic Predisposition to DiseaseGPI-Linked ProteinsGrowth ConesGrowth InhibitorsHumansMaleMiceMice, KnockoutMutationMyelin ProteinsNerve Fibers, MyelinatedNeurogenesisNeuronal PlasticityNogo Receptor 1Organ Culture TechniquesRatsReceptors, Cell SurfaceSchizophreniaConceptsMyelin inhibitionNogo-66 receptorCase-control analysisMyelin-specific genesAxonal sproutingMyelin signalGenetic predispositionAxon inhibitionNeuronal culturesPossible associationReceptor 1Disease riskAxon growthSchizophreniaAxonal proteinsPotential endophenotypeMemory functionGenetic variantsDysfunctional proteinsInhibitionSchizophrenia susceptibilityDominant negativeProtein exhibitCandidate genesChromosome 22q11
2006
Human clock, PER1 and PER2 polymorphisms: lack of association with cocaine dependence susceptibility and cocaine-induced paranoia
Malison RT, Kranzler HR, Yang BZ, Gelernter J. Human clock, PER1 and PER2 polymorphisms: lack of association with cocaine dependence susceptibility and cocaine-induced paranoia. Psychiatric Genetics 2006, 16: 245-249. PMID: 17106427, DOI: 10.1097/01.ypg.0000242198.59020.ca.Peer-Reviewed Original ResearchConceptsSingle nucleotide polymorphismsNucleotide polymorphismsCircadian rhythm genesDrosophila melanogasterHuman orthologGenetic variationCocaine-induced paranoiaGenetic mechanismsRhythm genesGene single nucleotide polymorphismsPopulation comparisonsHuman clockLack of associationPotential involvementAllelic associationClinical featuresAllele frequenciesStimulant exposureBehavioral sensitizationLocomotor sensitizationPsychostimulant addictionDrug useClinical phenotypeCocaine dependencePER2 polymorphisms