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 cessationGenetic 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
2022
Dissecting the epigenomic differences between smoking and nicotine dependence in a veteran cohort
Nagamatsu S, Pietrzak R, Xu K, Krystal J, Gelernter J, Montalvo‐Ortiz J. Dissecting the epigenomic differences between smoking and nicotine dependence in a veteran cohort. Addiction Biology 2022, 28: e13259. PMID: 36577721, DOI: 10.1111/adb.13259.Peer-Reviewed Original ResearchConceptsSmoking statusNicotine dependenceVeteran cohortNon-current smokersSerious public health issueNovel treatment strategiesPublic health issueUS military veteransEpigenome-wide association studiesCurrent smokersTreatment strategiesFagerström TestNicotine addictionSmokingHealth issuesRole of epigeneticsMilitary veteransMethylationEPIC BeadChip arraySmokersContinuous variablesF2RL3 geneCohortBiomarkersBeadChip arrayPrevious findings
2021
Multi-environment gene interactions linked to the interplay between polysubstance dependence and suicidality
Polimanti R, Levey DF, Pathak GA, Wendt FR, Nunez YZ, Ursano RJ, Kessler RC, Kranzler HR, Stein MB, Gelernter J. Multi-environment gene interactions linked to the interplay between polysubstance dependence and suicidality. Translational Psychiatry 2021, 11: 34. PMID: 33431810, PMCID: PMC7801457, DOI: 10.1038/s41398-020-01153-1.Peer-Reviewed Original ResearchConceptsSuicidal ideationPolysubstance dependenceSuicide attemptsOdds ratioGene-environment interactionsYale-PennMultivariate logistic regressionImportant risk factorMultivariate gene-environment interactionsMental health risksOpioid dependenceRisk factorsNicotine dependenceSuicidality outcomesCocaine dependenceLogistic regressionSubstance dependenceSuicidalityCohortLifetime suicidalityLinear mixed modelsMultiple substancesArmy STARRSArmy personnelHealth risks
2020
Diagnostic Reliability and Validity of the Semi-Structured Assessment for Drug Dependence and Alcoholism (SSADDA) Chinese Version
Yang BZ, Wang LJ, Huang MC, Wang SC, Tsai MC, Huang YC, Nuñez YZ, Ng MH, Kranzler HR, Gelernter J, Chen CK. Diagnostic Reliability and Validity of the Semi-Structured Assessment for Drug Dependence and Alcoholism (SSADDA) Chinese Version. Complex Psychiatry 2020, 6: 62-67. PMID: 34882761, PMCID: PMC7923924, DOI: 10.1159/000511606.Peer-Reviewed Original ResearchSD diagnosisSemi-Structured AssessmentTest-retest reliabilityDependence diagnosisDrug dependenceΚ statisticDiagnostic reliabilityStructured Clinical InterviewCohen κ statisticChance-corrected agreementClinician versionSubstance dependence diagnosesNicotine dependencePsychiatric disordersClinical InterviewAlcohol dependenceDSM-IVDiagnosisSubstance useChinese versionOpioidsValid instrumentConcurrent validityKetamineMethamphetamine
2017
Genome-wide association study across European and African American ancestries identifies a SNP in DNMT3B contributing to nicotine dependence
Hancock DB, Guo Y, Reginsson GW, Gaddis NC, Lutz SM, Sherva R, Loukola A, Minica CC, Markunas CA, Han Y, Young KA, Gudbjartsson DF, Gu F, McNeil DW, Qaiser B, Glasheen C, Olson S, Landi MT, Madden PAF, Farrer LA, Vink J, Saccone NL, Neale MC, Kranzler HR, McKay J, Hung RJ, Amos CI, Marazita ML, Boomsma DI, Baker TB, Gelernter J, Kaprio J, Caporaso NE, Thorgeirsson TE, Hokanson JE, Bierut LJ, Stefansson K, Johnson EO. Genome-wide association study across European and African American ancestries identifies a SNP in DNMT3B contributing to nicotine dependence. Molecular Psychiatry 2017, 23: 1911-1919. PMID: 28972577, PMCID: PMC5882602, DOI: 10.1038/mp.2017.193.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesAssociation studiesGenotype-Tissue Expression (GTEx) projectDNA methyltransferase genesAcetylcholine receptor genesNicotine dependenceMethyltransferase geneExpression projectCHRNB4 genesHeritable traitAdditional lociProxy phenotypeSequence variantsDNMT3B expressionGenesReceptor geneSquamous cell lung carcinomaCHRNA5-CHRNA3African American ancestryNovel associationsInternational Lung Cancer ConsortiumCell lung carcinomaLociAmerican ancestryAdult cerebellumSex Differences in Methamphetamine Use and Dependence in a Thai Treatment Center
Rungnirundorn T, Verachai V, Gelernter J, Malison RT, Kalayasiri R. Sex Differences in Methamphetamine Use and Dependence in a Thai Treatment Center. Journal Of Addiction Medicine 2017, 11: 19. PMID: 27649265, PMCID: PMC5291761, DOI: 10.1097/adm.0000000000000262.Peer-Reviewed Original ResearchConceptsMA dependenceMA useLifetime episodesTreatment centersLogistic regression analysisResidential drug treatmentChi-square testSex differencesSemi-Structured AssessmentAntisocial personality disorderMA diagnosisMA withdrawalTreatment cohortsComorbid antisocial personality disorderAssociated FactorsDrug treatmentSex-specific differencesNicotine dependencePsychomotor retardationDrug dependenceLogistic regressionMethamphetamine useMA usersPersonality disorderMethamphetamine
2016
CHRNA4 and ANKK1 Polymorphisms Influence Smoking-Induced Nicotinic Acetylcholine Receptor Upregulation
Esterlis I, Hillmer AT, Bois F, Pittman B, McGovern E, O’Malley S, Picciotto MR, Yang BZ, Gelernter J, Cosgrove KP. CHRNA4 and ANKK1 Polymorphisms Influence Smoking-Induced Nicotinic Acetylcholine Receptor Upregulation. Nicotine & Tobacco Research 2016, 18: 1845-1852. PMID: 27611310, PMCID: PMC4978979, DOI: 10.1093/ntr/ntw081.Peer-Reviewed Original ResearchMeSH KeywordsAdultCase-Control StudiesCorpus StriatumFemaleHumansIodine RadioisotopesMalePolymorphism, Single NucleotideProtein Serine-Threonine KinasesReceptors, NicotinicSmokingSmoking CessationSmoking PreventionTobacco Use DisorderTomography, Emission-Computed, Single-PhotonUp-RegulationWhite PeopleConceptsSmoking-induced changesWeeks of abstinenceNAChR availabilitySmoking cessationNicotine dependenceSex-matched nonsmokersTomography brain scanSingle nucleotide polymorphismsNicotinic acetylcholine receptorsSingle photon emissionDays of abstinenceNonsmoker levelsTobacco smokingReceptor upregulationBlood samplesAcetylcholine receptorsBrain scansCHRNA4 variantsCortical regionsSmokersCarrier statusExtended abstinenceAbstinencePersonalized programsNonsmokersCHRNA5/A3/B4 Variant rs3743078 and Nicotine-Related Phenotypes: Indirect Effects Through Nicotine Craving.
Shmulewitz D, Meyers JL, Wall MM, Aharonovich E, Frisch A, Spivak B, Weizman A, Edenberg HJ, Gelernter J, Hasin DS. CHRNA5/A3/B4 Variant rs3743078 and Nicotine-Related Phenotypes: Indirect Effects Through Nicotine Craving. Journal Of Studies On Alcohol And Drugs 2016, 77: 227-37. PMID: 26997181, PMCID: PMC4803655, DOI: 10.15288/jsad.2016.77.227.Peer-Reviewed Original ResearchConceptsNicotine cravingFTND scoreNeuronal nicotinic acetylcholine receptor geneNicotine use disorderNicotinic acetylcholine receptor genesAcetylcholine receptor genesLifetime smokersCigarette smokingMore cigarettesHigher scoresNicotine dependenceFagerström TestTherapeutic targetUse disordersG alleleAllele GCHRNA5-CHRNA3CravingReceptor geneScoresSizeable proportionFTNDCigarettesHousehold sampleSignificant indirect effect
2015
Genome-wide meta-analysis reveals common splice site acceptor variant in CHRNA4 associated with nicotine dependence
Hancock DB, Reginsson GW, Gaddis NC, Chen X, Saccone NL, Lutz SM, Qaiser B, Sherva R, Steinberg S, Zink F, Stacey SN, Glasheen C, Chen J, Gu F, Frederiksen BN, Loukola A, Gudbjartsson DF, Brüske I, Landi MT, Bickeböller H, Madden P, Farrer L, Kaprio J, Kranzler HR, Gelernter J, Baker TB, Kraft P, Amos CI, Caporaso NE, Hokanson JE, Bierut LJ, Thorgeirsson TE, Johnson EO, Stefansson K. Genome-wide meta-analysis reveals common splice site acceptor variant in CHRNA4 associated with nicotine dependence. Translational Psychiatry 2015, 5: e651-e651. PMID: 26440539, PMCID: PMC4930126, DOI: 10.1038/tp.2015.149.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesEuropean ancestry samplesNonsense-mediated decayWide significant associationsNicotinic receptor subunit geneReceptor subunit genesImportant regulatory propertiesNicotine dependenceSubunit geneAssociation studiesChromosome 20q13Regulatory propertiesLung cancer riskNovel variantsNormal human brainSmoking-related consequencesLung cancerCancer riskFagerström TestCHRNA4Smoking behaviorSignificant associationVariantsGenomeGenesAssociation of the OPRM1 Variant rs1799971 (A118G) with Non-Specific Liability to Substance Dependence in a Collaborative de novo Meta-Analysis of European-Ancestry Cohorts
Schwantes-An TH, Zhang J, Chen LS, Hartz SM, Culverhouse RC, Chen X, Coon H, Frank J, Kamens HM, Konte B, Kovanen L, Latvala A, Legrand LN, Maher BS, Melroy WE, Nelson EC, Reid MW, Robinson JD, Shen PH, Yang BZ, Andrews JA, Aveyard P, Beltcheva O, Brown SA, Cannon DS, Cichon S, Corley RP, Dahmen N, Degenhardt L, Foroud T, Gaebel W, Giegling I, Glatt SJ, Grucza RA, Hardin J, Hartmann AM, Heath AC, Herms S, Hodgkinson CA, Hoffmann P, Hops H, Huizinga D, Ising M, Johnson EO, Johnstone E, Kaneva RP, Kendler KS, Kiefer F, Kranzler HR, Krauter KS, Levran O, Lucae S, Lynskey MT, Maier W, Mann K, Martin NG, Mattheisen M, Montgomery GW, Müller-Myhsok B, Murphy MF, Neale MC, Nikolov MA, Nishita D, Nöthen MM, Nurnberger J, Partonen T, Pergadia ML, Reynolds M, Ridinger M, Rose RJ, Rouvinen-Lagerström N, Scherbaum N, Schmäl C, Soyka M, Stallings MC, Steffens M, Treutlein J, Tsuang M, Wall TL, Wodarz N, Yuferov V, Zill P, Bergen AW, Chen J, Cinciripini PM, Edenberg HJ, Ehringer MA, Ferrell RE, Gelernter J, Goldman D, Hewitt JK, Hopfer CJ, Iacono WG, Kaprio J, Kreek MJ, Kremensky IM, Madden PA, McGue M, Munafò MR, Philibert RA, Rietschel M, Roy A, Rujescu D, Saarikoski ST, Swan GE, Todorov AA, Vanyukov MM, Weiss RB, Bierut LJ, Saccone NL. Association of the OPRM1 Variant rs1799971 (A118G) with Non-Specific Liability to Substance Dependence in a Collaborative de novo Meta-Analysis of European-Ancestry Cohorts. Behavior Genetics 2015, 46: 151-169. PMID: 26392368, PMCID: PMC4752855, DOI: 10.1007/s10519-015-9737-3.Peer-Reviewed Original ResearchConceptsSubstance dependenceModest protective effectDSM-IV alcoholOpioid receptor geneLight smokingProtective effectNicotine dependenceAddiction liabilityDifferent addictive substancesG alleleMeta-AnalysisCocaine dependenceRs1799971Addictive substancesHuman genetic studiesReceptor genePotential functional significanceEuropean ancestry cohortsOPRM1Substance dependence riskSimilar effectsEuropean ancestry subjectsFunctional significanceAddictive behaviorsRisk
2013
Distinct Loci in the CHRNA5/CHRNA3/CHRNB4 Gene Cluster Are Associated With Onset of Regular Smoking
Stephens SH, Hartz SM, Hoft NR, Saccone NL, Corley RC, Hewitt JK, Hopfer CJ, Breslau N, Coon H, Chen X, Ducci F, Dueker N, Franceschini N, Frank J, Han Y, Hansel NN, Jiang C, Korhonen T, Lind PA, Liu J, Lyytikäinen L, Michel M, Shaffer JR, Short SE, Sun J, Teumer A, Thompson JR, Vogelzangs N, Vink JM, Wenzlaff A, Wheeler W, Yang B, Aggen SH, Balmforth AJ, Baumeister SE, Beaty TH, Benjamin DJ, Bergen AW, Broms U, Cesarini D, Chatterjee N, Chen J, Cheng Y, Cichon S, Couper D, Cucca F, Dick D, Foroud T, Furberg H, Giegling I, Gillespie NA, Gu F, Hall AS, Hällfors J, Han S, Hartmann AM, Heikkilä K, Hickie IB, Hottenga JJ, Jousilahti P, Kaakinen M, Kähönen M, Koellinger PD, Kittner S, Konte B, Landi M, Laatikainen T, Leppert M, Levy SM, Mathias RA, McNeil DW, Medland SE, Montgomery GW, Murray T, Nauck M, North KE, Paré PD, Pergadia M, Ruczinski I, Salomaa V, Viikari J, Willemsen G, Barnes KC, Boerwinkle E, Boomsma DI, Caporaso N, Edenberg HJ, Francks C, Gelernter J, Grabe HJ, Hops H, Jarvelin M, Johannesson M, Kendler KS, Lehtimäki T, Magnusson PK, Marazita ML, Marchini J, Mitchell BD, Nöthen MM, Penninx BW, Raitakari O, Rietschel M, Rujescu D, Samani NJ, Schwartz AG, Shete S, Spitz M, Swan GE, Völzke H, Veijola J, Wei Q, Amos C, Cannon DS, Grucza R, Hatsukami D, Heath A, Johnson EO, Kaprio J, Madden P, Martin NG, Stevens VL, Weiss RB, Kraft P, Bierut LJ, Ehringer MA. Distinct Loci in the CHRNA5/CHRNA3/CHRNB4 Gene Cluster Are Associated With Onset of Regular Smoking. Genetic Epidemiology 2013, 37: 846-859. PMID: 24186853, PMCID: PMC3947535, DOI: 10.1002/gepi.21760.Peer-Reviewed Original ResearchConceptsGene clusterAssociation signalsEarly smoking behaviourSmoking behaviorCHRNA5/A3/B4 gene clusterNicotinic acetylcholine receptor genesRobust association signalsNeuronal nicotinic acetylcholine receptor geneAcetylcholine receptor genesNicotine dependenceCHRNB4 gene clusterSignificant associationB4 gene clusterDistinct lociLung cancer riskRegular tobacco useAssociation resultsNicotine dependence phenotypesDependence phenotypesReceptor geneCotinine levelsRs1948PhenotypeRegular smokingProtective effect
2011
Childhood Adversity Increases Risk for Nicotine Dependence and Interacts with α5 Nicotinic Acetylcholine Receptor Genotype Specifically in Males
Xie P, Kranzler HR, Zhang H, Oslin D, Anton RF, Farrer LA, Gelernter J. Childhood Adversity Increases Risk for Nicotine Dependence and Interacts with α5 Nicotinic Acetylcholine Receptor Genotype Specifically in Males. Neuropsychopharmacology 2011, 37: 669-676. PMID: 22012472, PMCID: PMC3260970, DOI: 10.1038/npp.2011.240.Peer-Reviewed Original ResearchConceptsChildhood adversityRs16969968 genotypeND riskSex differencesNicotinic acetylcholine receptor genesAcetylcholine receptor genesPotential sex differencesNicotine dependence riskFagerstrom TestNicotine intakeSmoking riskIncrease riskNicotine dependenceRodent modelsReceptor genotypeND scoresEarly life experiencesEuropean AmericansReceptor geneWomenRiskGene × environment effectsMen
2010
Multiple Independent Loci at Chromosome 15q25.1 Affect Smoking Quantity: a Meta-Analysis and Comparison with Lung Cancer and COPD
Saccone NL, Culverhouse RC, Schwantes-An TH, Cannon DS, Chen X, Cichon S, Giegling I, Han S, Han Y, Keskitalo-Vuokko K, Kong X, Landi MT, Z. J, Short SE, Stephens SH, Stevens VL, Sun L, Wang Y, Wenzlaff AS, Aggen SH, Breslau N, Broderick P, Chatterjee N, Chen J, Heath AC, Heliövaara M, Hoft NR, Hunter DJ, Jensen MK, Martin NG, Montgomery GW, Niu T, Payne TJ, Peltonen L, Pergadia ML, Rice JP, Sherva R, Spitz MR, Sun J, Wang JC, Weiss RB, Wheeler W, Witt SH, Yang BZ, Caporaso NE, Ehringer MA, Eisen T, Gapstur SM, Gelernter J, Houlston R, Kaprio J, Kendler KS, Kraft P, Leppert MF, Li MD, Madden PA, Nöthen MM, Pillai S, Rietschel M, Rujescu D, Schwartz A, Amos CI, Bierut LJ. Multiple Independent Loci at Chromosome 15q25.1 Affect Smoking Quantity: a Meta-Analysis and Comparison with Lung Cancer and COPD. PLOS Genetics 2010, 6: e1001053. PMID: 20700436, PMCID: PMC2916847, DOI: 10.1371/journal.pgen.1001053.Peer-Reviewed Original ResearchConceptsChronic obstructive pulmonary diseaseLung cancerNicotine dependenceSmoking behaviorSmoking quantityObstructive pulmonary diseaseSmoking-related diseasesLung cancer casesPulmonary diseaseNicotinic receptor subunit geneCOPD casesIndependent associationLung tissueCancer casesReceptor subunit genesMeta-AnalysisSignificant associationSmokingRs16969968CancerSmoking phenotypesGenetic association findingsSNP rs16969968MRNA levelsCHRNA5-CHRNA3Meta-Analysis of 15 Genome-Wide Linkage Scans of Smoking Behavior
Han S, Gelernter J, Luo X, Yang BZ. Meta-Analysis of 15 Genome-Wide Linkage Scans of Smoking Behavior. Biological Psychiatry 2010, 67: 12-19. PMID: 19819424, PMCID: PMC2975396, DOI: 10.1016/j.biopsych.2009.08.028.Peer-Reviewed Original ResearchConceptsSmoking behaviorGenome-wide suggestive linkageGenome-wide linkage scanSubgroup analysisGenome scan resultsScan resultsLinkage scanSuggestive linkageGenome-wide significant linkageFagerstrom TestCandidate gene identificationNicotine dependenceRe-sequencing studiesMeta-AnalysisSecondary analysis