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 correlationsGenetic 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 cessationAssociation 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
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 loci
2016
Genome-wide association study of lifetime cannabis use based on a large meta-analytic sample of 32 330 subjects from the International Cannabis Consortium
Stringer S, Minică CC, Verweij KJ, Mbarek H, Bernard M, Derringer J, van Eijk KR, Isen JD, Loukola A, Maciejewski DF, Mihailov E, van der Most PJ, Sánchez-Mora C, Roos L, Sherva R, Walters R, Ware JJ, Abdellaoui A, Bigdeli TB, Branje SJ, Brown SA, Bruinenberg M, Casas M, Esko T, Garcia-Martinez I, Gordon SD, Harris JM, Hartman CA, Henders AK, Heath AC, Hickie IB, Hickman M, Hopfer CJ, Hottenga JJ, Huizink AC, Irons DE, Kahn RS, Korhonen T, Kranzler HR, Krauter K, van Lier PA, Lubke GH, Madden PA, Mägi R, McGue MK, Medland SE, Meeus WH, Miller MB, Montgomery GW, Nivard MG, Nolte IM, Oldehinkel AJ, Pausova Z, Qaiser B, Quaye L, Ramos-Quiroga JA, Richarte V, Rose RJ, Shin J, Stallings MC, Stiby AI, Wall TL, Wright MJ, Koot HM, Paus T, Hewitt JK, Ribasés M, Kaprio J, Boks MP, Snieder H, Spector T, Munafò MR, Metspalu A, Gelernter J, Boomsma DI, Iacono WG, Martin NG, Gillespie NA, Derks EM, Vink JM. Genome-wide association study of lifetime cannabis use based on a large meta-analytic sample of 32 330 subjects from the International Cannabis Consortium. Translational Psychiatry 2016, 6: e769-e769. PMID: 27023175, PMCID: PMC4872459, DOI: 10.1038/tp.2016.36.Peer-Reviewed Original ResearchConceptsLifetime cannabis useCannabis useInternational Cannabis ConsortiumLifetime cannabisIndividual differencesAutism disorderOccasional cannabisCannabis initiationSubstance useEffect sizeSocial consequencesCannabisLifetime cigarette smokingCigarette useReplication sampleGene-based testsCigarette smokingPsychoactive substancesIllicit psychoactive substancesSNP effect sizesFrequent useGenome-wide association studiesGenetic correlationsGenome-wide association dataAbuse