2024
Shared genetics of ADHD, cannabis use disorder and cannabis use and prediction of cannabis use disorder in ADHD
Nielsen T, Duan J, Levey D, Walters G, Johnson E, Thorgeirsson T, Werge T, Mortensen P, Stefansson H, Stefansson K, Hougaard D, Agrawal A, Gelernter J, Grove J, Børglum A, Demontis D. Shared genetics of ADHD, cannabis use disorder and cannabis use and prediction of cannabis use disorder in ADHD. Nature Mental Health 2024, 2: 1071-1083. DOI: 10.1038/s44220-024-00277-3.Peer-Reviewed Original ResearchAttention-deficit hyperactivity disorderCannabis use disorderCannabis useUse disorderPolygenic scoresComorbid cannabis use disorderStudies of attention-deficit hyperactivity disorderCross-disorder genome-wide association studySubstance-use disordersIncreased polygenic scoresBrain developmental stagesRisk genesCross-disorderConditions co-occurringPsychiatric disordersHyperactivity disorderGenome-wide significant lociSubstance useRare deleterious variantsCannabisDisordersSignificant lociDeleterious variantsSex-specific differencesBrainCross-ancestry genetic investigation of schizophrenia, cannabis use disorder, and tobacco smoking
Johnson E, Austin-Zimmerman I, Thorpe H, Levey D, Baranger D, Colbert S, Demontis D, Khokhar J, Davis L, Edenberg H, Di Forti M, Sanchez-Roige S, Gelernter J, Agrawal A. Cross-ancestry genetic investigation of schizophrenia, cannabis use disorder, and tobacco smoking. Neuropsychopharmacology 2024, 49: 1655-1665. PMID: 38906991, PMCID: PMC11399264, DOI: 10.1038/s41386-024-01886-3.Peer-Reviewed Original ResearchCannabis use disorderUse disorderPleiotropic lociCo-occurring substance useHeavy cannabis useInvestigation of schizophreniaSubstance use disordersGenome-wide studiesGenetic factorsMental health conditionsExecutive functionCannabis useSubstance useLead variantsSchizophreniaGenetic variantsEuropean ancestryEuropean ancestry dataRisk-takingSCZHeritable factorsCannabisDisordersTobacco smokeGenetic correlationsGene × environment effects and mediation involving adverse childhood events, mood and anxiety disorders, and substance dependence
Kranzler H, Davis C, Feinn R, Jinwala Z, Khan Y, Oikonomou A, Silva-Lopez D, Burton I, Dixon M, Milone J, Ramirez S, Shifman N, Levey D, Gelernter J, Hartwell E, Kember R. Gene × environment effects and mediation involving adverse childhood events, mood and anxiety disorders, and substance dependence. Nature Human Behaviour 2024, 8: 1616-1627. PMID: 38834750, DOI: 10.1038/s41562-024-01885-w.Peer-Reviewed Original ResearchAdverse childhood eventsSubstance dependenceMood/anxiety disordersAnxiety disordersChildhood eventsIndirect associationsGenetic riskExposure to adverse childhood eventsDevelopment of moodSubstance use disordersAssociations of adverse childhood eventsUse disorderMediation modelMood/anxietyDisorder factorsPolygenic scoresIndirect pathsDisordersEuropean ancestry individualsMoodTreatment approachesAnxietySelf-medicationEuropean ancestryLatent variablesDissecting the Relationships Between Cannabis Use Disorder and Schizophrenia Using Genome-Wide Approaches
Johnson E, Levey D, Baranger D, Colbert S, Gelernter J, Agrawal A. Dissecting the Relationships Between Cannabis Use Disorder and Schizophrenia Using Genome-Wide Approaches. Biological Psychiatry 2024, 95: s28-s29. DOI: 10.1016/j.biopsych.2024.02.075.Peer-Reviewed Original ResearchGenetic 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 cessation
2022
Genetic variants associated with psychiatric disorders are enriched at epigenetically active sites in lymphoid cells
Lynall ME, Soskic B, Hayhurst J, Schwartzentruber J, Levey DF, Pathak GA, Polimanti R, Gelernter J, Stein MB, Trynka G, Clatworthy MR, Bullmore E. Genetic variants associated with psychiatric disorders are enriched at epigenetically active sites in lymphoid cells. Nature Communications 2022, 13: 6102. PMID: 36243721, PMCID: PMC9569335, DOI: 10.1038/s41467-022-33885-7.Peer-Reviewed Original ResearchConceptsMultiple psychiatric disordersPsychiatric disordersPsychiatric risk variantT cellsLymphoid cellsRisk variantsImmune cell subsetsMental health disordersMultiple organ systemsAdaptive immune systemCell subsetsImmune cellsHealth disordersMyeloid cellsImmune systemBrain tissueOrgan systemsSpecific disordersDisordersPathogenesisAbnormalitiesGenetic variantsCellsCD4VariantsAn Atlas of Genetic Correlations and Genetically Informed Associations Linking Psychiatric and Immune-Related Phenotypes
Tylee DS, Lee YK, Wendt FR, Pathak GA, Levey DF, De Angelis F, Gelernter J, Polimanti R. An Atlas of Genetic Correlations and Genetically Informed Associations Linking Psychiatric and Immune-Related Phenotypes. JAMA Psychiatry 2022, 79: 667-676. PMID: 35507366, PMCID: PMC9069342, DOI: 10.1001/jamapsychiatry.2022.0914.Peer-Reviewed Original ResearchConceptsRisk factorsImmune-related phenotypesMultivariable adjustmentUlcerative colitisCrohn's diseaseMendelian randomizationImmune-related disordersReciprocal risk factorsHealth-related behaviorsPsychiatric phenotypesFalse discovery rate correctionAllergic rhinitisGenetic association studiesGenetic associationInflammatory disordersClinical associationsMajor depressionImmune disordersMAIN OUTCOMEPsychiatric disordersSocial determinantsDisordersAssociation studiesColitisAsthma
2021
Psychological trauma and the genetic overlap between posttraumatic stress disorder and major depressive disorder
Mundy J, Hübel C, Gelernter J, Levey D, Murray RM, Skelton M, Stein MB, Maihofer A, Nievergelt C, Baker D, Risborough V, Calabrese J, Galea S, Stein D, Koen N, Dalvie S, Aiello A, Roberts A, Koenen K, Solovieff N, Kranzler H, Zhao H, Gelernter J, Farrer L, Johnson E, Rice J, Bierut L, Saccone N, McFarlane A, Forbes D, Silove D, O'Donnell M, Bryant R, van Hooff M, Sponheim S, Disner S, Pietrzak R, Chen C, Smoller J, Stein M, Ursano R, Kessler R, Junglen A, Delahanty D, Amstadter A, Sheerin C, Ruggiero K, McLaughlin K, Peverill M, Caldas-de-Almeida J, Austin S, Gelaye B, Williams M, Sanchez S, Franz C, Panizzon M, Lyons M, Kremen W, Andreassen O, Dale A, Rutten B, Vinkers C, Schijven D, Geuze E, Vermetten E, Luykx J, Boks M, Ashley-Koch A, Beckham J, Garrett M, Hauser M, Dennis M, Kimbrel N, Qin X, Karstoft K, Andersen S, Borglum A, Hougaard D, Bybjerg-Grauholm J, Duncan L, Bµkvad-Hansen M, Nordentoft M, Mors O, Mortensen P, Werge T, Thompson W, Wang Y, Heath A, Nelson E, Martin N, Gordon S, Wolf E, Logue M, Miller M, McGlinchey R, Milberg W, Erbes C, Polusny M, Arbisi P, Peterson A, Williamson D, Young K, Maurer D, Rothbaum A, Zoellner L, Mavissakalian M, Feeny N, Roy-Byrne P, Rothbaum B, Maples-Keller J, Khan A, Wolff J, Lebois L, Teicher M, Kaufman M, Winternitz S, Bolger E, Seligowski A, Orcutt H, Evans A, Lugonja B, Lewis C, Jones I, Bisson J, McLean S, Linnstaedt S, Peters E, Rung A, Trapido E, Brashear M, Lori A, Smith A, Bradley B, Gillespie C, Guffanti G, Ressler K, Almli L, Jovanovic T, Bustamante A, Uddin M, van den Heuvel L, Seedat S, Hemmings S, Uka A, Kulenovic A, Wolf C, Babic D, Avdibegovic E, Deckert J, Domschke K, Jakovljevic M, Marmar C, Flory J, Jett M, Yehuda R, Hammamieh R, King A, Liberzon I, Seng J, Morris C, Mehta D, Voisey J, Lawford B, Young R, McLeay S, Daskalakis N, Norman S, Wang Z, Breen G, Coleman J, Klengel T, Torres K, Choi K, Levey D, Polimanti R, Atkinson E, Martin A, Neale B, Daly M, Ripke S, Ratanatharathorn A, Provost A, Haas M, Stevens J, Morey R, Harnal S, Mortensen P, Seedat S, Sumner J, Vassos E, Breen G, Coleman J. Psychological trauma and the genetic overlap between posttraumatic stress disorder and major depressive disorder. Psychological Medicine 2021, 52: 3975-3984. PMID: 34085609, PMCID: PMC8962503, DOI: 10.1017/s0033291721000830.Peer-Reviewed Original ResearchRecurrent major depressive disorderMajor depressive disorderPosttraumatic stress disorderSingle-episode major depressive disorderDepressive disorderTrauma exposureStress disorderPsychological trauma exposureLifetime major depressive disorderTrauma sensitivityGenetic loadingUK Biobank participantsKey risk factorsMental health consequencesRisk factorsMillion Veteran ProgramPolygenic risk scoresRisk scoreGenetic overlapHealth consequencesBiobank participantsTraumaDisordersVeteran ProgramPsychiatric Genomics Consortium