Featured Publications
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 diseasesTSNARE1FBXW4Phenome-wide Association Analysis of Substance Use Disorders in a Deeply Phenotyped Sample
Kember RL, Hartwell EE, Xu H, Rotenberg J, Almasy L, Zhou H, Gelernter J, Kranzler HR. Phenome-wide Association Analysis of Substance Use Disorders in a Deeply Phenotyped Sample. Biological Psychiatry 2022, 93: 536-545. PMID: 36273948, PMCID: PMC9931661, DOI: 10.1016/j.biopsych.2022.08.010.Peer-Reviewed Original ResearchConceptsSubstance use disordersAlcohol use disorderOpioid use disorderPolygenic risk scoresUse disordersCo-occurring psychiatric disordersComprehensive psychiatric interviewSemi-Structured AssessmentElectronic health recordsControl subjectsLow prevalencePsychiatric interviewRisk scorePsychiatric disordersPhenome-wide association analysisDrug dependenceEuropean individualsHealth recordsLifetime cannabisPhenome-wide association studyDisordersAfrican ancestry individualsDSM diagnosesPopulation sampleGenetic liability
2024
Genetic influences and causal pathways shared between cannabis use disorder and other substance use traits
Galimberti M, Levey D, Deak J, Zhou H, Stein M, Gelernter J. Genetic influences and causal pathways shared between cannabis use disorder and other substance use traits. Molecular Psychiatry 2024, 29: 2905-2910. PMID: 38580809, PMCID: PMC11419938, DOI: 10.1038/s41380-024-02548-y.Peer-Reviewed Original ResearchSubstance use disordersProblematic alcohol useSubstance use traitsCannabis use disorderCannabis useOpioid use disorderUse disorderGenomic structural equation modelingSmoking initiationLifetime cannabis useLegalization of cannabis useGlobal genetic correlationsProblematic substance useStructural equation modelingNicotine dependenceGenetic influencesCannabisSubstance useFagerstrom TestAlcohol useMendelian randomizationBidirectional relationshipGenetic correlationsDisordersSmoking cessationA multi-ancestry genetic study of pain intensity in 598,339 veterans
Toikumo S, Vickers-Smith R, Jinwala Z, Xu H, Saini D, Hartwell E, Pavicic M, Sullivan K, Xu K, Jacobson D, Gelernter J, Rentsch C, Stahl E, Cheatle M, Zhou H, Waxman S, Justice A, Kember R, Kranzler H. A multi-ancestry genetic study of pain intensity in 598,339 veterans. Nature Medicine 2024, 30: 1075-1084. PMID: 38429522, DOI: 10.1038/s41591-024-02839-5.Peer-Reviewed Original ResearchPain intensityChronic painTreat chronic painCalcium channel blockersCross-ancestry meta-analysisGenome-wide association studiesExperience of painSamples of European ancestryPain phenotypesFunctional genomics dataGABAergic neuronsCalcium channelsAnalgesic effectB-blockersDrug groupMillion Veteran ProgramPainSubstance use disordersQuality of lifeDrug repurposing analysisOpioid crisisGenetic architectureCausal genesGenetic lociGenomic dataPleiotropy and genetically inferred causality linking multisite chronic pain to substance use disorders
Koller D, Friligkou E, Stiltner B, Pathak G, Løkhammer S, Levey D, Zhou H, Hatoum A, Deak J, Kember R, Treur J, Kranzler H, Johnson E, Stein M, Gelernter J, Polimanti R. Pleiotropy and genetically inferred causality linking multisite chronic pain to substance use disorders. Molecular Psychiatry 2024, 29: 2021-2030. PMID: 38355787, PMCID: PMC11324857, DOI: 10.1038/s41380-024-02446-3.Peer-Reviewed Original ResearchMultisite chronic painSubstance use disordersChronic painUK BiobankUse disorderMillion Veteran ProgramSNP-based heritabilityGenome-wide association statisticsMR analysisPotential causal relationshipVeteran ProgramPleiotropy analysisTobacco usePleiotropic variantsOpioid use disorderAssociation statisticsCannabis use disorderAlcohol use disorderMeta-analysesBrain-wide analysisImaging phenotypesBi-directional relationshipPainPleiotropyBiobankGenetic contribution to the comorbidity between attention-deficit/hyperactivity disorder and substance use disorders
Koller D, Mitjans M, Kouakou M, Friligkou E, Cabrera-Mendoza B, Deak J, Llonga N, Pathak G, Stiltner B, Løkhammer S, Levey D, Zhou H, Hatoum A, Kember R, Kranzler H, Stein M, Corominas R, Demontis D, Artigas M, Ramos-Quiroga J, Gelernter J, Ribasés M, Cormand B, Polimanti R. Genetic contribution to the comorbidity between attention-deficit/hyperactivity disorder and substance use disorders. Psychiatry Research 2024, 333: 115758. PMID: 38335780, PMCID: PMC11157987, DOI: 10.1016/j.psychres.2024.115758.Peer-Reviewed Original ResearchConceptsUse disorderGenome-wide association studiesGenomic structural equation modelingCannabis use disorderAlcohol Use Disorders Identification TestAttention-deficit/hyperactivity disorderAlcohol use disorderProblematic alcohol useSubstance use disordersTwo-sample Mendelian randomization analysisLinkage disequilibrium score regression analysisDisorders Identification TestMendelian randomization analysisAssociated with increased oddsOdds of ADHDOpioid use disorderAttention-deficit/hyperactivityGWAS meta-analysesAlcohol dependenceStructural equation modelingNicotine dependenceInvestigate genetic correlationsADHDPolygenic riskStrength of evidence
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