Featured Publications
Multi-ancestry genome-wide association study of cannabis use disorder yields insight into disease biology and public health implications
Levey D, Galimberti M, Deak J, Wendt F, Bhattacharya A, Koller D, Harrington K, Quaden R, Johnson E, Gupta P, Biradar M, Lam M, Cooke M, Rajagopal V, Empke S, Zhou H, Nunez Y, Kranzler H, Edenberg H, Agrawal A, Smoller J, Lencz T, Hougaard D, Børglum A, Demontis D, Gaziano J, Gandal M, Polimanti R, Stein M, Gelernter J. Multi-ancestry genome-wide association study of cannabis use disorder yields insight into disease biology and public health implications. Nature Genetics 2023, 55: 2094-2103. PMID: 37985822, PMCID: PMC10703690, DOI: 10.1038/s41588-023-01563-z.Peer-Reviewed Original ResearchConceptsSingle nucleotide polymorphism-based heritabilityMulti-ancestry genome-wide association studyAssociation studiesMillion Veteran ProgramGenome-wide association studiesWide significant lociWide association studySignificant lociReference panelSmall populationDisease biologyAncestryAmerican ancestryHeritabilityVeteran ProgramNumerous medical comorbiditiesLung cancer riskRelationship analysisLociBiologyPublic health implicationsEast AsiansPublic health consequencesMedical comorbiditiesCigarette smoking
2020
A large-scale genome-wide association study meta-analysis of cannabis use disorder
Johnson EC, Demontis D, Thorgeirsson TE, Walters RK, Polimanti R, Hatoum AS, Sanchez-Roige S, Paul SE, Wendt FR, Clarke TK, Lai D, Reginsson GW, Zhou H, He J, Baranger DAA, Gudbjartsson DF, Wedow R, Adkins DE, Adkins AE, Alexander J, Bacanu SA, Bigdeli TB, Boden J, Brown SA, Bucholz KK, Bybjerg-Grauholm J, Corley RP, Degenhardt L, Dick DM, Domingue BW, Fox L, Goate AM, Gordon SD, Hack LM, Hancock DB, Hartz SM, Hickie IB, Hougaard DM, Krauter K, Lind PA, McClintick JN, McQueen MB, Meyers JL, Montgomery GW, Mors O, Mortensen PB, Nordentoft M, Pearson JF, Peterson RE, Reynolds MD, Rice JP, Runarsdottir V, Saccone NL, Sherva R, Silberg JL, Tarter RE, Tyrfingsson T, Wall TL, Webb BT, Werge T, Wetherill L, Wright MJ, Zellers S, Adams MJ, Bierut LJ, Boardman JD, Copeland WE, Farrer LA, Foroud TM, Gillespie NA, Grucza RA, Harris KM, Heath AC, Hesselbrock V, Hewitt JK, Hopfer CJ, Horwood J, Iacono WG, Johnson EO, Kendler KS, Kennedy MA, Kranzler HR, Madden PAF, Maes HH, Maher BS, Martin NG, McGue M, McIntosh AM, Medland SE, Nelson EC, Porjesz B, Riley BP, Stallings MC, Vanyukov MM, Vrieze S, Workgroup P, Walters R, Polimanti R, Johnson E, McClintick J, Hatoum A, He J, Wendt F, Zhou H, Adams M, Adkins A, Aliev F, Bacanu S, Batzler A, Bertelsen S, Biernacka J, Bigdeli T, Chen L, Clarke T, Chou Y, Degenhardt F, Docherty A, Edwards A, Fontanillas P, Foo J, Fox L, Frank J, Giegling I, Gordon S, Hack L, Hartmann A, Hartz S, Heilmann-Heimbach S, Herms S, Hodgkinson C, Hoffman P, Hottenga J, Kennedy M, Alanne-Kinnunen M, Konte B, Lahti J, Lahti-Pulkkinen M, Lai D, Ligthart L, Loukola A, Maher B, Mbarek H, McIntosh A, McQueen M, Meyers J, Milaneschi Y, Palviainen T, Pearson J, Peterson R, Ripatti S, Ryu E, Saccone N, Salvatore J, Sanchez-Roige S, Schwandt M, Sherva R, Streit F, Strohmaier J, Thomas N, Wang J, Webb B, Wedow R, Wetherill L, Wills A, Boardman J, Chen D, Choi D, Copeland W, Culverhouse R, Dahmen N, Degenhardt L, Domingue B, Elson S, Frye M, Gäbel W, Hayward C, Ising M, Keyes M, Kiefer F, Kramer J, Kuperman S, Lucae S, Lynskey M, Maier W, Mann K, Männistö S, Müller-Myhsok B, Murray A, Nurnberger J, Palotie A, Preuss U, Räikkönen K, Reynolds M, Ridinger M, Scherbaum N, Schuckit M, Soyka M, Treutlein J, Witt S, Wodarz N, Zill P, Adkins D, Boden J, Boomsma D, Bierut L, Brown S, Bucholz K, Cichon S, Costello E, de Wit H, Diazgranados N, Dick D, Eriksson J, Farrer L, Foroud T, Gillespie N, Goate A, Goldman D, Grucza R, Hancock D, Harris K, Heath A, Hesselbrock V, Hewitt J, Hopfer C, Horwood J, Iacono W, Johnson E, Kaprio J, Karpyak V, Kendler K, Kranzler H, Krauter K, Lichtenstein P, Lind P, McGue M, MacKillop J, Madden P, Maes H, Magnusson P, Martin N, Medland S, Montgomery G, Nelson E, Nöthen M, Palmer A, Pederson N, Penninx B, Porjesz B, Rice J, Rietschel M, Riley B, Rose R, Rujescu D, Shen P, Silberg J, Stallings M, Tarter R, Vanyukov M, Vrieze S, Wall T, Whitfield J, Zhao H, Neale B, Gelernter J, Edenberg H, Agrawal A, Davis L, Bogdan R, Gelernter J, Edenberg H, Stefansson K, Børglum A, Agrawal A. A large-scale genome-wide association study meta-analysis of cannabis use disorder. The Lancet Psychiatry 2020, 7: 1032-1045. PMID: 33096046, PMCID: PMC7674631, DOI: 10.1016/s2215-0366(20)30339-4.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesAssociation studiesGenome-wide significant lociLarge-scale genome-wide association studiesGenetic correlationsChromosome 7 locusTraits of interestLarge genome-wide association studiesLinkage disequilibrium score regressionChromosome 8 locusDifferent genetic underpinningsDifferent genetic correlationsWellcome Trust Case Control ConsortiumDisequilibrium score regressionNovel genetic variantsStrong genetic componentSignificant lociGenetic lociGenetic underpinningsGenetic componentLociScore regressionGenetic variantsGenetic overlapIntegrative sequencing
2018
GWAS 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 analysisTranslational 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
2017
Genome-wide association study identifies a novel locus for cannabis dependence
Agrawal A, Chou YL, Carey CE, Baranger DAA, Zhang B, Sherva R, Wetherill L, Kapoor M, Wang JC, Bertelsen S, Anokhin AP, Hesselbrock V, Kramer J, Lynskey MT, Meyers JL, Nurnberger JI, Rice JP, Tischfield J, Bierut LJ, Degenhardt L, Farrer LA, Gelernter J, Hariri AR, Heath AC, Kranzler HR, Madden PAF, Martin NG, Montgomery GW, Porjesz B, Wang T, Whitfield JB, Edenberg HJ, Foroud T, Goate AM, Bogdan R, Nelson EC. Genome-wide association study identifies a novel locus for cannabis dependence. Molecular Psychiatry 2017, 23: 1293-1302. PMID: 29112194, PMCID: PMC5938138, DOI: 10.1038/mp.2017.200.Peer-Reviewed Original ResearchMeSH KeywordsAdultAllelesBlack or African AmericanCannabisCase-Control StudiesChromosomes, Human, Pair 10Cohort StudiesFemaleGene FrequencyGenetic Predisposition to DiseaseGenome-Wide Association StudyGenotypeHumansMaleMarijuana AbuseMiddle AgedPhenotypePolymorphism, Single NucleotideWhite PeopleYoung AdultConceptsWide significant lociSingle nucleotide polymorphismsSignificant lociGenome-wide significant lociGenome-wide association study dataGenome-wide association studiesAssociation study dataCorrelated single-nucleotide polymorphismsNovel lociTranscription factorsChromosome 10Association studiesModerate heritabilityNovel regionLociBiological contributionEA college studentsMinor alleleEuropean descentH3K4me1Criterion countsHeritabilityPhenotypeEnhancerIndependent cohortS100A10 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 studyCohort
2016
Genome-wide Association Study of Cannabis Dependence Severity, Novel Risk Variants, and Shared Genetic Risks
Sherva R, Wang Q, Kranzler H, Zhao H, Koesterer R, Herman A, Farrer LA, Gelernter J. Genome-wide Association Study of Cannabis Dependence Severity, Novel Risk Variants, and Shared Genetic Risks. JAMA Psychiatry 2016, 73: 472. PMID: 27028160, PMCID: PMC4974817, DOI: 10.1001/jamapsychiatry.2016.0036.Peer-Reviewed Original ResearchConceptsCannabis dependenceNeuronal calcium homeostasisGenetic factorsMajor depressive disorderSushi multiple domains-1 (CSMD1) geneSubstance abuse treatment centersSpecific genetic risk factorsGenetic risk factorsShared genetic riskPotential genetic factorsCentral nervous system developmentCriterion countsCannabis dependence severityDomain 1 geneCAD riskMean ageRisk factorsDepressive disorderNervous system developmentMajor depressionLarge cohortMAIN OUTCOMEGenome-wide association studiesTreatment centersCalcium homeostasisGenome-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
2014
Evaluating the role of a galanin enhancer genotype on a range of metabolic, depressive and addictive phenotypes
Richardson TG, Minica C, Heron J, Tavare J, MacKenzie A, Day I, Lewis G, Hickman M, Vink JM, Gelernter J, Kranzler HR, Farrer LA, Munafò M, Wynick D. Evaluating the role of a galanin enhancer genotype on a range of metabolic, depressive and addictive phenotypes. American Journal Of Medical Genetics Part B Neuropsychiatric Genetics 2014, 165: 654-664. PMID: 25228436, PMCID: PMC4388908, DOI: 10.1002/ajmg.b.32270.Peer-Reviewed Original ResearchConceptsRat hypothalamic neuronsAvon Longitudinal StudyGalaninergic systemGalanin expressionNeuropeptide galaninHypothalamic neuronsClinical dataChild CohortEnhancer region upstreamGG alleleCannabis usageYoung adultsCA alleleLongitudinal studyPathological functionsTransfection studiesInitial findingsGalaninCohortNeuronsCharacteristics and course of dependence in cocaine-dependent individuals who never used alcohol or marijuana or used cocaine first.
Sartor CE, Kranzler HR, Gelernter J. Characteristics and course of dependence in cocaine-dependent individuals who never used alcohol or marijuana or used cocaine first. Journal Of Studies On Alcohol And Drugs 2014, 75: 423-7. PMID: 24766754, PMCID: PMC4002856, DOI: 10.15288/jsad.2014.75.423.Peer-Reviewed Original Research
2012
Identification of POMC Exonic Variants Associated with Substance Dependence and Body Mass Index
Wang F, Gelernter J, Kranzler HR, Zhang H. Identification of POMC Exonic Variants Associated with Substance Dependence and Body Mass Index. PLOS ONE 2012, 7: e45300. PMID: 23028917, PMCID: PMC3444488, DOI: 10.1371/journal.pone.0045300.Peer-Reviewed Original ResearchConceptsBody mass indexSubstance dependenceMass indexExact testRare variantsAfrican AmericansNormal weight groupCommon variantsFisher's exact testProopiomelanocortin geneObese groupObese subjectsExonic variantsMelanocortin peptidesEuropean AmericansLogistic regressionCommon polymorphismsOverweightRare exonic variantsVariants AssociatedPopulation-specific mannerRiskAssociationObesityGroupHypermethylation of OPRM1 promoter region in European Americans with alcohol dependence
Zhang H, Herman AI, Kranzler HR, Anton RF, Simen AA, Gelernter J. Hypermethylation of OPRM1 promoter region in European Americans with alcohol dependence. Journal Of Human Genetics 2012, 57: 670-675. PMID: 22914673, PMCID: PMC3481015, DOI: 10.1038/jhg.2012.98.Peer-Reviewed Original ResearchMeSH KeywordsAdultAlcoholismCase-Control StudiesCocaine-Related DisordersComorbidityCpG IslandsDNA MethylationFemaleGenetic Predisposition to DiseaseGenetics, PopulationGenome, HumanHumansMaleMarijuana AbuseMiddle AgedMultivariate AnalysisPromoter Regions, GeneticReceptors, Opioid, muRisk FactorsSequence Analysis, DNAWhite PeopleConceptsChildhood adversityOPRM1 promoter regionAD casesΜ-opioid receptor geneSubstance dependence disordersΜ-opioid receptorDays of intoxicationEffects of alcoholEuropean American controlsPromoter methylation levelsPeripheral bloodMethylation levelsDependence disordersAlcohol dependenceMultivariate analysisPromoter regionPromoter hypermethylationReceptor geneIllicit drugsEuropean AmericansMultiple comparisonsBisulfite sequencing analysisOverall methylation levelsAmerican controlsSexPrevalence of DSM-IV and DSM-5 alcohol, cocaine, opioid, and cannabis use disorders in a largely substance dependent sample
Peer K, Rennert L, Lynch KG, Farrer L, Gelernter J, Kranzler HR. Prevalence of DSM-IV and DSM-5 alcohol, cocaine, opioid, and cannabis use disorders in a largely substance dependent sample. Drug And Alcohol Dependence 2012, 127: 215-219. PMID: 22884164, PMCID: PMC3727225, DOI: 10.1016/j.drugalcdep.2012.07.009.Peer-Reviewed Original ResearchConceptsSubstance use disordersSUD diagnosisDSM-IVDiagnosis of SUDDSM-5DSM-5 substance use disordersDSM-5 SUD diagnosesDiagnostic orphansSevere substance use disordersLimited diagnostic utilityDSM-5 diagnosisDSM-5 alcoholSemi-Structured AssessmentDSM-IV abuseDiagnostic switchLifetime presenceClinical careDiagnostic criteriaGreater prevalenceUse disordersDiagnostic utilityDependence diagnosisMental disordersDrug dependenceSubstance dependenceVariation in regulator of G-protein signaling 17 gene (RGS17) is associated with multiple substance dependence diagnoses
Zhang H, Wang F, Kranzler HR, Anton RF, Gelernter J. Variation in regulator of G-protein signaling 17 gene (RGS17) is associated with multiple substance dependence diagnoses. Behavioral And Brain Functions 2012, 8: 23. PMID: 22591552, PMCID: PMC3406967, DOI: 10.1186/1744-9081-8-23.Peer-Reviewed Original ResearchAdultAlcoholismBlack or African AmericanCocaine-Related DisordersFemaleGenetic VariationHaplotypesHumansLinkage DisequilibriumMaleMarijuana AbuseMiddle AgedOpioid-Related DisordersPolymorphism, Single NucleotideRGS ProteinsRisk FactorsSignal TransductionSubstance-Related DisordersUnited StatesWhite PeopleLinkage Analysis Followed by Association Show NRG1 Associated with Cannabis Dependence in African Americans
Han S, Yang BZ, Kranzler HR, Oslin D, Anton R, Farrer LA, Gelernter J. Linkage Analysis Followed by Association Show NRG1 Associated with Cannabis Dependence in African Americans. Biological Psychiatry 2012, 72: 637-644. PMID: 22520967, PMCID: PMC3699339, DOI: 10.1016/j.biopsych.2012.02.038.Peer-Reviewed Original ResearchConceptsSingle nucleotide polymorphismsSusceptibility genesLinkage peakGenome-wide linkage scanAssociation analysisGenome-wide association studiesStudy of AddictionStrong linkage evidenceChromosome 8p21.1AA sampleLinkage scanLocal ancestryAssociation studiesGenetic studiesLinkage analysisReplicated associationsLinkage evidenceGenetic variantsGenesNucleotide polymorphismsGenetic contributionGeneticsNRG1Environment samplesReplication study