2020
Transcriptomic organization of the human brain in post-traumatic stress disorder
Girgenti MJ, Wang J, Ji D, Cruz DA, Stein M, Gelernter J, Young K, Huber B, Williamson D, Friedman M, Krystal J, Zhao H, Duman R. Transcriptomic organization of the human brain in post-traumatic stress disorder. Nature Neuroscience 2020, 24: 24-33. PMID: 33349712, DOI: 10.1038/s41593-020-00748-7.Peer-Reviewed Original ResearchMeSH KeywordsAdultAutopsyBrain ChemistryCohort StudiesDepressive Disorder, MajorFemaleGene Expression RegulationGene Regulatory NetworksGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansInterneuronsMaleMiddle AgedNerve Tissue ProteinsSex CharacteristicsStress Disorders, Post-TraumaticTranscriptomeYoung AdultConceptsGenome-wide association studiesSignificant gene networksDifferential gene expressionSystems-level evidenceSignificant genetic liabilityMajor depressive disorder cohortGene networksTranscriptomic organizationTranscriptomic landscapeDownregulated setsGenomic networksGene expressionAssociation studiesMolecular determinantsExtensive remodelingGenotype dataSexual dimorphismSignificant divergenceMolecular profileNetwork analysisELFN1TranscriptsDimorphismPostmortem tissueDivergence
2019
Salivary microRNAs identified by small RNA sequencing and machine learning as potential biomarkers of alcohol dependence
Rosato AJ, Chen X, Tanaka Y, Farrer LA, Kranzler HR, Nunez YZ, Henderson DC, Gelernter J, Zhang H. Salivary microRNAs identified by small RNA sequencing and machine learning as potential biomarkers of alcohol dependence. Epigenomics 2019, 11: 739-749. PMID: 31140863, PMCID: PMC6595542, DOI: 10.2217/epi-2018-0177.Peer-Reviewed Original Research
2018
Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder
Demontis D, Walters RK, Martin J, Mattheisen M, Als TD, Agerbo E, Baldursson G, Belliveau R, Bybjerg-Grauholm J, Bækvad-Hansen M, Cerrato F, Chambert K, Churchhouse C, Dumont A, Eriksson N, Gandal M, Goldstein JI, Grasby KL, Grove J, Gudmundsson OO, Hansen CS, Hauberg ME, Hollegaard MV, Howrigan DP, Huang H, Maller JB, Martin AR, Martin NG, Moran J, Pallesen J, Palmer DS, Pedersen CB, Pedersen MG, Poterba T, Poulsen JB, Ripke S, Robinson EB, Satterstrom FK, Stefansson H, Stevens C, Turley P, Walters GB, Won H, Wright MJ, Andreassen O, Asherson P, Burton C, Boomsma D, Cormand B, Dalsgaard S, Franke B, Gelernter J, Geschwind D, Hakonarson H, Haavik J, Kranzler H, Kuntsi J, Langley K, Lesch K, Middeldorp C, Reif A, Rohde L, Roussos P, Schachar R, Sklar P, Sonuga-Barke E, Sullivan P, Thapar A, Tung J, Waldman I, Medland S, Stefansson K, Nordentoft M, Hougaard D, Werge T, Mors O, Mortensen P, Daly M, Faraone S, Børglum A, Neale B. Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder. Nature Genetics 2018, 51: 63-75. PMID: 30478444, PMCID: PMC6481311, DOI: 10.1038/s41588-018-0269-7.Peer-Reviewed Original ResearchConceptsGenome-wide significant risk lociFunction intolerant genesGenome-wide associationSignificant risk lociGenome-wide significanceAttention-deficit/hyperactivity disorderCommon genetic variantsGenomic regionsIntolerant genesIndependent lociRegulatory marksHeritable traitRisk lociDeficit/hyperactivity disorderGenetic variantsGenetic overlapStudy-specific differencesLociHyperactivity disorderImportant new informationUnderlying biologyChildhood behavioral disordersVariantsStrong concordanceGWASGWAS of lifetime cannabis use reveals new risk loci, genetic overlap with psychiatric traits, and a causal effect of schizophrenia liability
Pasman JA, Verweij KJH, Gerring Z, Stringer S, Sanchez-Roige S, Treur JL, Abdellaoui A, Nivard MG, Baselmans BML, Ong JS, Ip HF, van der Zee MD, Bartels M, Day FR, Fontanillas P, Elson SL, the 23andMe Research Team, de Wit H, Davis LK, MacKillop J, The Substance Use Disorders Working Group of the Psychiatric Genomics Consortium, International Cannabis Consortium, Derringer JL, Branje SJT, Hartman CA, Heath AC, van Lier PAC, Madden PAF, Mägi R, Meeus W, Montgomery GW, Oldehinkel AJ, Pausova Z, Ramos-Quiroga JA, Paus T, Ribases M, Kaprio J, Boks MPM, Bell JT, Spector TD, Gelernter J, Boomsma DI, Martin NG, MacGregor S, Perry JRB, Palmer AA, Posthuma D, Munafò MR, Gillespie NA, Derks EM, Vink JM. GWAS of lifetime cannabis use reveals new risk loci, genetic overlap with psychiatric traits, and a causal effect of schizophrenia liability. Nature Neuroscience 2018, 21: 1161-1170. PMID: 30150663, PMCID: PMC6386176, DOI: 10.1038/s41593-018-0206-1.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAged, 80 and overCell Adhesion MoleculesDatabases, GeneticFemaleGene Expression RegulationGenetic Predisposition to DiseaseGenome-Wide Association StudyGenotypeHumansMaleMarijuana AbuseMendelian Randomization AnalysisMental HealthMiddle AgedPolymorphism, Single NucleotideRisk-TakingSchizophreniaYoung AdultConceptsGenome-wide association studiesNew risk lociLarge genome-wide association studiesGene-based testsIndependent single nucleotide polymorphismsDifferent expression levelsSignificant genetic correlationsHealth-related traitsSingle nucleotide polymorphismsEtiology of cannabisHeritable traitRisk lociSignificant genesAssociation studiesGenetic correlationsPsychiatric traitsGenetic variantsNucleotide polymorphismsGenetic overlapExpression levelsTraitsGenesNew insightsSchizophrenia riskMendelian randomization analysis
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 differencesA 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
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
Exome sequencing and genome-wide copy number variant mapping reveal novel associations with sensorineural hereditary hearing loss
Haraksingh RR, Jahanbani F, Rodriguez-Paris J, Gelernter J, Nadeau KC, Oghalai JS, Schrijver I, Snyder MP. Exome sequencing and genome-wide copy number variant mapping reveal novel associations with sensorineural hereditary hearing loss. BMC Genomics 2014, 15: 1155. PMID: 25528277, PMCID: PMC4367882, DOI: 10.1186/1471-2164-15-1155.Peer-Reviewed Original ResearchConceptsHearing lossHereditary hearing lossExome sequencingSensorineural hearing lossType II myosinGenome-wide CNV analysisCase-control cohortNon-syndromic sensorineural hearing lossStrong candidate geneLoss patientsDirect clinical applicationGenetic diversityNovel lociClinical settingCytoskeletal proteinsCandidate genesCandidate lociVariants mappingDistinct familiesChromosome 16Loss phenotypeClinical applicationNovel regionLociCNV analysisDifferentially 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
2013
Sex-biased methylome and transcriptome in human prefrontal cortex
Xu H, Wang F, Liu Y, Yu Y, Gelernter J, Zhang H. Sex-biased methylome and transcriptome in human prefrontal cortex. Human Molecular Genetics 2013, 23: 1260-1270. PMID: 24163133, PMCID: PMC3919013, DOI: 10.1093/hmg/ddt516.Peer-Reviewed Original ResearchConceptsDNA methylationGene expressionSex-biased DNA methylationMultiple test correctionGenome-wide DNA methylationGene Ontology annotationsDAVID functional annotation analysisFunctional annotation analysisRibosome structurePhenotypic variationAnnotation analysisGO termsProtein translationRNA bindingOntology annotationsHost genesDifferential methylationExpression correlationTranscriptomic profilesDifferential brain developmentDifferential expressionMethylation levelsGenesMethylationTranscriptome
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
2010
Functional impact of a single-nucleotide polymorphism in the OPRD1 promoter region
Zhang H, Gelernter J, Gruen JR, Kranzler HR, Herman AI, Simen AA. Functional impact of a single-nucleotide polymorphism in the OPRD1 promoter region. Journal Of Human Genetics 2010, 55: 278-284. PMID: 20300121, PMCID: PMC2876206, DOI: 10.1038/jhg.2010.22.Peer-Reviewed Original ResearchMeSH KeywordsAllelesCell LineElectrophoretic Mobility Shift AssayGene Expression RegulationHumansLuciferasesNuclear ProteinsOligonucleotide ProbesPolymorphism, Single NucleotidePromoter Regions, GeneticProtein BindingReceptors, Opioid, deltaRecombinant Fusion ProteinsTranscription FactorsTransfectionConceptsMinor G alleleG alleleΔ-opioid receptorsSubstances of abuseDual-luciferase reporterOpioid dependenceBrain nuclear proteinsGreater expression levelsA alleleLuciferase reporterRenilla luciferase vectorsSingle nucleotide polymorphismsLuciferase reporter vectorExpression levelsPromoter regionHEK293 cellsLuciferase vectorFunctional impactLuciferase expressionFunctional significanceExpressionRenilla luciferase expressionReporter vectorTranscription factors
2003
Synonymous mutations in the human dopamine receptor D2 (DRD2) affect mRNA stability and synthesis of the receptor
Duan J, Wainwright MS, Comeron JM, Saitou N, Sanders AR, Gelernter J, Gejman PV. Synonymous mutations in the human dopamine receptor D2 (DRD2) affect mRNA stability and synthesis of the receptor. Human Molecular Genetics 2003, 12: 205-216. PMID: 12554675, DOI: 10.1093/hmg/ddg055.Peer-Reviewed Original ResearchConceptsSynonymous mutationsMRNA stabilitySynonymous variationMolecular population geneticsSynonymous codon usage biasThird codon positionCodon usage biasNovel genetic mechanismGene mapping studiesStructure of proteinsFunctional effectsSynonymous positionsPopulation geneticsSynonymous changesUsage biasCodon positionsDNA sequencesNucleotide sequenceGenetic mechanismsComplex inheritanceNucleotide substitutionsDopamine receptor D2Linkage disequilibriumEuropean American populationFunctional consequences