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
Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder
Demontis D, Walters RK, Martin J, Mattheisen M, Als TD, Agerbo E, Baldursson G, Belliveau R, Bybjerg-Grauholm J, Bækvad-Hansen M, Cerrato F, Chambert K, Churchhouse C, Dumont A, Eriksson N, Gandal M, Goldstein JI, Grasby KL, Grove J, Gudmundsson OO, Hansen CS, Hauberg ME, Hollegaard MV, Howrigan DP, Huang H, Maller JB, Martin AR, Martin NG, Moran J, Pallesen J, Palmer DS, Pedersen CB, Pedersen MG, Poterba T, Poulsen JB, Ripke S, Robinson EB, Satterstrom FK, Stefansson H, Stevens C, Turley P, Walters GB, Won H, Wright MJ, Andreassen O, Asherson P, Burton C, Boomsma D, Cormand B, Dalsgaard S, Franke B, Gelernter J, Geschwind D, Hakonarson H, Haavik J, Kranzler H, Kuntsi J, Langley K, Lesch K, Middeldorp C, Reif A, Rohde L, Roussos P, Schachar R, Sklar P, Sonuga-Barke E, Sullivan P, Thapar A, Tung J, Waldman I, Medland S, Stefansson K, Nordentoft M, Hougaard D, Werge T, Mors O, Mortensen P, Daly M, Faraone S, Børglum A, Neale B. Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder. Nature Genetics 2018, 51: 63-75. PMID: 30478444, PMCID: PMC6481311, DOI: 10.1038/s41588-018-0269-7.Peer-Reviewed Original ResearchConceptsGenome-wide significant risk lociFunction intolerant genesGenome-wide associationSignificant risk lociGenome-wide significanceAttention-deficit/hyperactivity disorderCommon genetic variantsGenomic regionsIntolerant genesIndependent lociRegulatory marksHeritable traitRisk lociDeficit/hyperactivity disorderGenetic variantsGenetic overlapStudy-specific differencesLociHyperactivity disorderImportant new informationUnderlying biologyChildhood behavioral disordersVariantsStrong concordanceGWAS
2017
A putative causal relationship between genetically determined female body shape and posttraumatic stress disorder
Polimanti R, Amstadter AB, Stein MB, Almli LM, Baker DG, Bierut LJ, Bradley B, Farrer LA, Johnson EO, King A, Kranzler HR, Maihofer AX, Rice JP, Roberts AL, Saccone NL, Zhao H, Liberzon I, Ressler KJ, Nievergelt CM, Koenen KC, Gelernter J, for The Psychiatric Genomics Consortium Posttraumatic Stress Disorder Workgroup. A putative causal relationship between genetically determined female body shape and posttraumatic stress disorder. Genome Medicine 2017, 9: 99. PMID: 29178946, PMCID: PMC5702961, DOI: 10.1186/s13073-017-0491-4.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesLarge genome-wide association studiesPutative causal relationshipAnthropometric traitsBody shapeEvolutionary mechanismsTop associationsAssociation studiesReproductive behaviorGenetic correlationsPleiotropic effectsGenetic overlapFemale body shapePolygenic score approachTraitsMendelian randomization analysisSummary statisticsRandomization analysisHuman sexual behaviorMechanismApolipoprotein E gene polymorphism, trauma burden, and posttraumatic stress symptoms in U.S. military veterans: Results from the National Health and Resilience in Veterans Study
Mota NP, Han S, Harpaz‐Rotem I, Maruff P, Krystal JH, Southwick SM, Gelernter J, Pietrzak RH. Apolipoprotein E gene polymorphism, trauma burden, and posttraumatic stress symptoms in U.S. military veterans: Results from the National Health and Resilience in Veterans Study. Depression And Anxiety 2017, 35: 168-177. PMID: 29172227, PMCID: PMC5794529, DOI: 10.1002/da.22698.Peer-Reviewed Original ResearchConceptsΕ4 allele carriersApolipoprotein E gene polymorphismE gene polymorphismTrauma burdenU.S. military veteransAllele carriersPosttraumatic stress disorderPTSD symptomsNational HealthGreater social supportGene polymorphismsGreater severityMilitary veteransVeterans StudyAPOE ε4 carrier statusSocial supportΕ4 carrier statusAPOE genotypeΕ4 noncarriersPosttraumatic stress symptomsIndependent replication sampleSymptomsPTSD riskStress disorderCarrier statusCortical β-amyloid burden, gray matter, and memory in adults at varying APOE ε4 risk for Alzheimer's disease
Mecca AP, Barcelos NM, Wang S, Brück A, Nabulsi N, Planeta-Wilson B, Nadelmann J, Benincasa AL, Ropchan J, Huang Y, Gelernter J, Van Ness PH, Carson RE, van Dyck CH. Cortical β-amyloid burden, gray matter, and memory in adults at varying APOE ε4 risk for Alzheimer's disease. Neurobiology Of Aging 2017, 61: 207-214. PMID: 29111487, PMCID: PMC5722236, DOI: 10.1016/j.neurobiolaging.2017.09.027.Peer-Reviewed Original ResearchConceptsΒ-amyloid burdenMiddle-aged individualsAβ burdenEpisodic memory performanceCognitive declineGM fractionCortical β-amyloid burdenBrain magnetic resonance imagingFirst-degree family historyCortical Aβ burdenGray matter fractionNormal middle-aged individualsSubsequent cognitive declineMagnetic resonance imagingPositron emission tomographyAPOE ε3ε3Cortical AβCerebral amyloidosisAPOE genotypeFamily historyPreclinical ADMemory performanceNeuropsychological testingAlzheimer's diseaseGray matter
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 homeostasis
2015
Eye color: A potential indicator of alcohol dependence risk in European Americans
Sulovari A, Kranzler HR, Farrer LA, Gelernter J, Li D. Eye color: A potential indicator of alcohol dependence risk in European Americans. American Journal Of Medical Genetics Part B Neuropsychiatric Genetics 2015, 168: 347-353. PMID: 25921801, DOI: 10.1002/ajmg.b.32316.Peer-Reviewed Original ResearchConceptsAlcohol dependenceLight-eyed individualsDark-eyed individualsPopulation-based studyLight eye colorBlue eye colorEvidence of associationEye colorRisk factorsEtiological factorsHigh prevalenceEye color geneLogistic regressionAD-associated genesMore alcoholArchival samplesColor genesAssociationEuropean ancestry subjectsReceptor gene clusterIndividualsStratificationBrown eye colorFurther characterizationAssociation studies
2014
Genetic risk prediction and neurobiological understanding of alcoholism
Levey DF, Le-Niculescu H, Frank J, Ayalew M, Jain N, Kirlin B, Learman R, Winiger E, Rodd Z, Shekhar A, Schork N, Kiefe F, Wodarz N, Müller-Myhsok B, Dahmen N, Nöthen M, Sherva R, Farrer L, Smith A, Kranzler H, Rietschel M, Gelernter J, Niculescu A. Genetic risk prediction and neurobiological understanding of alcoholism. Translational Psychiatry 2014, 4: e391-e391. PMID: 24844177, PMCID: PMC4035721, DOI: 10.1038/tp.2014.29.Peer-Reviewed Original ResearchConceptsTop candidate genesCandidate genesGenetic risk predictionGenome-wide association study dataFunctional genomics approachConvergent functional genomics approachAssociation study dataGene expression dataInitial discovery stepGenomic approachesKey genesSignal transductionSignificant genetic overlapTop genesRelevant genesBiological pathwaysExpression dataTop findingsGenesStrict Bonferroni correctionGenetic overlapProtein knockout miceSmall panelFatty acidsKnockout miceThe effects of a MAP2K5 microRNA target site SNP on risk for anxiety and depressive disorders
Jensen KP, Kranzler HR, Stein MB, Gelernter J. The effects of a MAP2K5 microRNA target site SNP on risk for anxiety and depressive disorders. American Journal Of Medical Genetics Part B Neuropsychiatric Genetics 2014, 165: 175-183. PMID: 24436253, PMCID: PMC4174417, DOI: 10.1002/ajmg.b.32219.Peer-Reviewed Original ResearchConceptsGene-trait relationshipsGWAS-identified variantsRegulation of mRNAGWAS signalsComplex traitsTrait associationsTarget genesStudy signalsSNP associationsRisk genesFunctional variantsSNPsGenesAnxiety-related traitsGene SNPsTraitsMRNAMAP2K5MicroRNAsMajor psychiatric disordersVariantsSite informationMitogenRegulationPathway
2011
No association between ADCYAP1R1 and post-traumatic stress disorder in two independent samples
Chang SC, Xie P, Anton RF, De Vivo I, Farrer LA, Kranzler HR, Oslin D, Purcell SM, Roberts AL, Smoller JW, Uddin M, Gelernter J, Koenen KC. No association between ADCYAP1R1 and post-traumatic stress disorder in two independent samples. Molecular Psychiatry 2011, 17: 239-241. PMID: 21912390, DOI: 10.1038/mp.2011.118.Peer-Reviewed Original ResearchAdultAge FactorsAgedBlack PeopleCohort StudiesFemaleGenotypeHumansLogistic ModelsMaleMenopauseMiddle AgedPolymorphism, Single NucleotideProspective StudiesReceptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type IRiskSample SizeSelection BiasSocioeconomic FactorsStress Disorders, Post-TraumaticSubstance-Related DisordersUnited StatesWhite People
2010
Interaction of FKBP5 with Childhood Adversity on Risk for Post-Traumatic Stress Disorder
Xie P, Kranzler HR, Poling J, Stein MB, Anton RF, Farrer LA, Gelernter J. Interaction of FKBP5 with Childhood Adversity on Risk for Post-Traumatic Stress Disorder. Neuropsychopharmacology 2010, 35: 1684-1692. PMID: 20393453, PMCID: PMC2946626, DOI: 10.1038/npp.2010.37.Peer-Reviewed Original ResearchConceptsChildhood adverse experiencesChildhood adversitySingle nucleotide polymorphismsFKBP5 polymorphismsAdverse experiencesAfrican AmericansPost-traumatic stress disorder symptomsChildhood adversity exposureLogistic regression analysisChildhood abusePost-traumatic stress disorderRisk of PTSDCortisol-binding affinityDepressive episodeLifetime PTSDFKBP5 genotypeHigh riskTT genotypeLower riskRecurrence riskGlucocorticoid receptorAlcohol dependenceFKBP5 locusStress disorderFKBP5
2007
The OPRD1 and OPRK1 loci in alcohol or drug dependence: OPRD1 variation modulates substance dependence risk
Zhang H, Kranzler HR, Yang BZ, Luo X, Gelernter J. The OPRD1 and OPRK1 loci in alcohol or drug dependence: OPRD1 variation modulates substance dependence risk. Molecular Psychiatry 2007, 13: 531-543. PMID: 17622222, PMCID: PMC3163084, DOI: 10.1038/sj.mp.4002035.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAlcoholismCase-Control StudiesCocaine-Related DisordersEuropeExonsFemaleGenetic Predisposition to DiseaseHaplotypesHeroin DependenceHumansLinkage DisequilibriumMaleMiddle AgedPolymorphism, Single NucleotideReceptors, Opioid, deltaReceptors, Opioid, kappaRiskSubstance-Related DisordersUnited StatesConceptsLogistic regression analysisSingle nucleotide polymorphismsRegression analysisTag single nucleotide polymorphismsOPRD1 variantsG alleleC alleleDrug dependenceSignificant associationRisk effectsEuropean AmericansStratification artifactSignificant differencesPositive associationHaplotypic associationsMultiple testingAssociationOPRK1OPRD1Dependence riskSD
2006
Genetic and Environmental Predictors of Early Alcohol Use
Kaufman J, Yang BZ, Douglas-Palumberi H, Crouse-Artus M, Lipschitz D, Krystal JH, Gelernter J. Genetic and Environmental Predictors of Early Alcohol Use. Biological Psychiatry 2006, 61: 1228-1234. PMID: 17123474, DOI: 10.1016/j.biopsych.2006.06.039.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAlcohol DrinkingAllelesChildChild AbuseChild, PreschoolCohort StudiesDNAFemaleFollow-Up StudiesGenetic VariationGenotypeHumansMaleMental DisordersPredictive Value of TestsPrognosisPsychiatric Status Rating ScalesRiskSerotonin Plasma Membrane Transport ProteinsSocial EnvironmentSocial SupportStress Disorders, Post-TraumaticConceptsEarly alcohol useAlcohol useMaltreated childrenLater alcohol dependenceSubstance use disordersSubstance abuse problemsHigh riskMother-child relationsAlcohol dependenceSeverity of maltreatmentProtective factorsHome careIntervention effortsPotent predictorCommunity controlsAbuse problemsTransporter genotypeChildrenPredictorsMaltreatmentRiskApolipoprotein E ɛ4 Allele Increases Risk for Psychotic Symptoms in Alzheimer's Disease
Zdanys KF, Kleiman TG, MacAvoy MG, Black BT, Rightmer TE, Grey M, Garman KS, Tampi RR, Gelernter J, van Dyck CH. Apolipoprotein E ɛ4 Allele Increases Risk for Psychotic Symptoms in Alzheimer's Disease. Neuropsychopharmacology 2006, 32: 171-179. PMID: 16841077, DOI: 10.1038/sj.npp.1301148.Peer-Reviewed Original ResearchConceptsAD patientsPsychotic symptomsAlzheimer's diseaseBehavioral symptomsNeuropsychiatric InventoryApolipoprotein EMultiple logistic regression modelSporadic Alzheimer's diseaseGenetic risk factorsSevere-stage Alzheimer's diseaseLogistic regression modelsDifferent risk profilesDementia progressesRisk factorsIncrease riskBehavioral disturbancesPatientsDisease severitySymptomsSignificant psychosisRisk profileGreater riskApoEExploratory analysisDiseaseDiplotype Trend Regression Analysis of the ADH Gene Cluster and the ALDH2 Gene: Multiple Significant Associations with Alcohol Dependence
Luo X, Kranzler HR, Zuo L, Wang S, Schork NJ, Gelernter J. Diplotype Trend Regression Analysis of the ADH Gene Cluster and the ALDH2 Gene: Multiple Significant Associations with Alcohol Dependence. American Journal Of Human Genetics 2006, 78: 973-987. PMID: 16685648, PMCID: PMC1474098, DOI: 10.1086/504113.Peer-Reviewed Original ResearchConceptsADH gene clusterGene clusterAldehyde dehydrogenase geneStructured association analysisConventional association methodsALDH2 geneAlcohol dehydrogenaseAdh geneDehydrogenase geneAssociation analysisSusceptibility lociGenesRisk genesFunctional variantsDisease allelesFunctional complexityCase-control sampleAncestry informative markersHardy-Weinberg equilibrium testDisequilibrium measuresMultiple significant associationsAllelesAlcohol-metabolizing enzymesConventional case-control comparisonsUnlinked ancestry-informative markers
2004
Results of a genomewide linkage scan: Support for chromosomes 9 and 11 loci increasing risk for cigarette smoking
Gelernter J, Liu X, Hesselbrock V, Page GP, Goddard A, Zhang H. Results of a genomewide linkage scan: Support for chromosomes 9 and 11 loci increasing risk for cigarette smoking. American Journal Of Medical Genetics Part B Neuropsychiatric Genetics 2004, 128B: 94-101. PMID: 15211640, DOI: 10.1002/ajmg.b.30019.Peer-Reviewed Original Research