2024
Association between cannabis use and brain structure and function: an observational and Mendelian randomisation study
Ishrat S, Levey D, Gelernter J, Ebmeier K, Topiwala A. Association between cannabis use and brain structure and function: an observational and Mendelian randomisation study. BMJ Mental Health 2024, 27: e301065. PMID: 39477366, PMCID: PMC11529520, DOI: 10.1136/bmjment-2024-301065.Peer-Reviewed Original ResearchConceptsCannabis useBrain structuresFunctional connectivityHistory of cannabis useResting-state functional connectivityMeasures of brain structureLifetime cannabis useCentral executive networkLifetime cannabis usersWhite matter integrityGenu of the corpus callosumMendelian randomisation analysisAssociated with multiple measuresPoorer white matter integrityInvestigate potential causal relationshipsCannabis usersExecutive networkBrain regionsImaging-derived phenotypesBrain healthCannabisRandomisation analysesTwo-sample Mendelian randomisation analysisFractional anisotropyYoung adulthood
2023
Genome-wide association study of antisocial personality disorder diagnostic criteria provides evidence for shared risk factors across disorders
Li W, Zhou H, Thygesen J, Heydtmann M, Smith I, Degenhardt F, Nöthen M, Morgan M, Kranzler H, Gelernter J, Bass N, McQuillin A. Genome-wide association study of antisocial personality disorder diagnostic criteria provides evidence for shared risk factors across disorders. Psychiatric Genetics 2023, 33: 233-242. PMID: 37756443, PMCID: PMC10635348, DOI: 10.1097/ypg.0000000000000352.Peer-Reviewed Original ResearchConceptsAntisocial personality disorderAttention deficit hyperactivity disorderSubstance use disordersPosttraumatic stress disorderGenome-wide association studiesDeficit hyperactivity disorderDisorder diagnostic criteriaRisk factorsFrontal cortexDiagnostic criteriaUse disordersRisk score analysisAnterior cingulateAlcohol-dependent participantsPsychiatric conditionsSignificant associationBrain regionsPersonality disorder diagnostic criteriaStress disorderAnxiety disordersASPD criteriaHyperactivity disorderPolygenic risk score analysisPersonality disorderScore analysis
2022
Cross-ancestry meta-analysis of opioid use disorder uncovers novel loci with predominant effects in brain regions associated with addiction
Kember RL, Vickers-Smith R, Xu H, Toikumo S, Niarchou M, Zhou H, Hartwell EE, Crist RC, Rentsch CT, Davis L, Justice A, Sanchez-Roige S, Kampman K, Gelernter J, Kranzler H. Cross-ancestry meta-analysis of opioid use disorder uncovers novel loci with predominant effects in brain regions associated with addiction. Nature Neuroscience 2022, 25: 1279-1287. PMID: 36171425, PMCID: PMC9682545, DOI: 10.1038/s41593-022-01160-z.Peer-Reviewed Original ResearchConceptsOpioid use disorderGenome-wide association studiesWide significant lociGene expression enrichmentSignificant genetic correlationsCell type groupSignificant lociAssociation studiesExpression enrichmentMillion Veteran ProgramGenetic correlationsUse disordersLociBrain regionsExonic variantsIntronic variantsSubstance use disordersTraitsBiological basisOpioid epidemicPsychiatric disordersVeteran ProgramBrain diseasesTSNARE1FBXW4Associations between moderate alcohol consumption, brain iron, and cognition in UK Biobank participants: Observational and mendelian randomization analyses
Topiwala A, Wang C, Ebmeier KP, Burgess S, Bell S, Levey DF, Zhou H, McCracken C, Roca-Fernández A, Petersen SE, Raman B, Husain M, Gelernter J, Miller KL, Smith SM, Nichols TE. Associations between moderate alcohol consumption, brain iron, and cognition in UK Biobank participants: Observational and mendelian randomization analyses. PLOS Medicine 2022, 19: e1004039. PMID: 35834561, PMCID: PMC9282660, DOI: 10.1371/journal.pmed.1004039.Peer-Reviewed Original ResearchConceptsAlcohol use disorderHigh brain ironModerate alcohol consumptionBrain ironAlcohol consumptionAlcohol intakeUse disordersSubstantia nigraAlcohol-related cognitive declineIron depositionBrain regionsSusceptibility-weighted magnetic resonanceIron accumulationIron levelsBrain iron depositionBrain iron levelsSystemic iron levelsSystemic iron storesAlcohol-related cognitive deficitsBasal ganglia ironElevated liver ironMendelian randomizationWeekly alcohol consumptionUK Biobank participantsExecutive function
2017
S100A10 identified in a genome-wide gene × cannabis dependence interaction analysis of risky sexual behaviours
Polimanti R, Meda SA, Pearlson GD, Zhao H, Sherva R, Farrer LA, Kranzler HR, Gelernter J. S100A10 identified in a genome-wide gene × cannabis dependence interaction analysis of risky sexual behaviours. Journal Of Psychiatry And Neuroscience 2017, 42: 252-261. PMID: 28418321, PMCID: PMC5487272, DOI: 10.1503/jpn.160189.Peer-Reviewed Original ResearchConceptsRisky sexual behaviorCAD diagnosisLow-frequency fluctuation (ALFF) analysisMultiple sexual partnersLeft paracentral lobuleSexual behaviorAfrican American cohortSemi-Structured AssessmentALFF analysisSexual functionAfrican American participantsCalcium-binding proteinsParacentral lobuleIndependent cohortRight pallidumCalcium homeostasisUnprotected sexCannabis dependenceDrug dependenceSignificant associationBrain regionsSexual partnersFrequency fluctuation analysisPrevious genome-wide association studyCohortPhenome-wide association study for CYP2A6 alleles: rs113288603 is associated with hearing loss symptoms in elderly smokers
Polimanti R, Jensen KP, Gelernter J. Phenome-wide association study for CYP2A6 alleles: rs113288603 is associated with hearing loss symptoms in elderly smokers. Scientific Reports 2017, 7: 1034. PMID: 28432340, PMCID: PMC5430682, DOI: 10.1038/s41598-017-01098-4.Peer-Reviewed Original ResearchConceptsLoss symptomsElderly subjectsAge-related hearing lossPhenome-wide association studyElderly smokersCigarette smokingNovel phenotypic associationsCerebellar hemisphereAuditory functionDiscovery cohortHearing lossReplication cohortBrain regionsSignificant associationNicotine metabolismCYP2A6 expressionCYP2A6 allelesMember 6Association studiesSmokingCohortSymptomsAssociationRegulatory roleInvolvement
2008
Allelic Variation of Calsyntenin 2 (CLSTN2) Modulates the Impact of Developmental Tobacco Smoke Exposure on Mnemonic Processing in Adolescents
Jacobsen LK, Picciotto MR, Heath CJ, Mencl WE, Gelernter J. Allelic Variation of Calsyntenin 2 (CLSTN2) Modulates the Impact of Developmental Tobacco Smoke Exposure on Mnemonic Processing in Adolescents. Biological Psychiatry 2008, 65: 671-679. PMID: 19058786, PMCID: PMC2864130, DOI: 10.1016/j.biopsych.2008.10.024.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdolescent BehaviorAdolescent DevelopmentAllelic ImbalanceBrainCalcium-Binding ProteinsFemaleGenotypeHumansIntracellular Signaling Peptides and ProteinsMaleMembrane ProteinsMemory DisordersPhosphoproteinsPregnancyPrenatal Exposure Delayed EffectsProteinsTemporal LobeTobacco Smoke PollutionConceptsAdolescent exposureCalsyntenin-2Visuospatial memoryMedial temporal lobe functionRecall of wordsRecognition memory taskFunctional magnetic resonance imaging (fMRI) dataTemporal lobe functionEnhanced functional connectivityMemory taskVerbal recallMnemonic processingVerbal recognitionIndividual differencesAdolescent developmentLobe functionKIBRA genotypeDependent measuresMagnetic resonance imaging dataFunctional connectivityParahippocampal gyrusSubsequent deficitsBrain regionsMemoryAdolescents
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