Featured Publications
Genetics of substance use disorders in the era of big data
Gelernter J, Polimanti R. Genetics of substance use disorders in the era of big data. Nature Reviews Genetics 2021, 22: 712-729. PMID: 34211176, PMCID: PMC9210391, DOI: 10.1038/s41576-021-00377-1.Peer-Reviewed Original Research
2024
Association 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
2022
Cross-ancestry meta-analysis of opioid use disorder uncovers novel loci with predominant effects in brain regions associated with addiction
Kember RL, Vickers-Smith R, Xu H, Toikumo S, Niarchou M, Zhou H, Hartwell EE, Crist RC, Rentsch CT, Davis L, Justice A, Sanchez-Roige S, Kampman K, Gelernter J, Kranzler H. Cross-ancestry meta-analysis of opioid use disorder uncovers novel loci with predominant effects in brain regions associated with addiction. Nature Neuroscience 2022, 25: 1279-1287. PMID: 36171425, PMCID: PMC9682545, DOI: 10.1038/s41593-022-01160-z.Peer-Reviewed Original ResearchConceptsOpioid use disorderGenome-wide association studiesWide significant lociGene expression enrichmentSignificant genetic correlationsCell type groupSignificant lociAssociation studiesExpression enrichmentMillion Veteran ProgramGenetic correlationsUse disordersLociBrain regionsExonic variantsIntronic variantsSubstance use disordersTraitsBiological basisOpioid epidemicPsychiatric disordersVeteran ProgramBrain diseasesTSNARE1FBXW4Integrating human brain proteomic data with genome-wide association study findings identifies novel brain proteins in substance use traits
Toikumo S, Xu H, Gelernter J, Kember RL, Kranzler HR. Integrating human brain proteomic data with genome-wide association study findings identifies novel brain proteins in substance use traits. Neuropsychopharmacology 2022, 47: 2292-2299. PMID: 35941285, PMCID: PMC9630289, DOI: 10.1038/s41386-022-01406-1.Peer-Reviewed Original ResearchConceptsSubstance use traitsProteome-wide association studyUse traitsProtein abundanceAssociation studiesBrain protein abundanceWide association studyGenome-wide association study summary statisticsHuman brain proteomeFine-mapping analysisGenetic risk lociBrain transcriptomic dataEuropean ancestry individualsOpioid use disorderProteomic abundanceTranscriptomic levelTranscriptomic dataAlcohol use disorderProteomic dataBrain proteomeGenetic lociTranscript levelsRisk lociGene expressionSignificant genesAssociations between moderate alcohol consumption, brain iron, and cognition in UK Biobank participants: Observational and mendelian randomization analyses
Topiwala A, Wang C, Ebmeier KP, Burgess S, Bell S, Levey DF, Zhou H, McCracken C, Roca-Fernández A, Petersen SE, Raman B, Husain M, Gelernter J, Miller KL, Smith SM, Nichols TE. Associations between moderate alcohol consumption, brain iron, and cognition in UK Biobank participants: Observational and mendelian randomization analyses. PLOS Medicine 2022, 19: e1004039. PMID: 35834561, PMCID: PMC9282660, DOI: 10.1371/journal.pmed.1004039.Peer-Reviewed Original ResearchConceptsAlcohol use disorderHigh brain ironModerate alcohol consumptionBrain ironAlcohol consumptionAlcohol intakeUse disordersSubstantia nigraAlcohol-related cognitive declineIron depositionBrain regionsSusceptibility-weighted magnetic resonanceIron accumulationIron levelsBrain iron depositionBrain iron levelsSystemic iron levelsSystemic iron storesAlcohol-related cognitive deficitsBasal ganglia ironElevated liver ironMendelian randomizationWeekly alcohol consumptionUK Biobank participantsExecutive functionGenome-wide meta-analysis of insomnia prioritizes genes associated with metabolic and psychiatric pathways
Watanabe K, Jansen PR, Savage JE, Nandakumar P, Wang X, Hinds D, Gelernter J, Levey D, Polimanti R, Stein M, Van Someren E, Smit A, Posthuma D. Genome-wide meta-analysis of insomnia prioritizes genes associated with metabolic and psychiatric pathways. Nature Genetics 2022, 54: 1125-1132. PMID: 35835914, DOI: 10.1038/s41588-022-01124-w.Peer-Reviewed Original ResearchConceptsRisk lociGenome-wide association studiesSpecific gene setsPrevious genome-wide association studyGene prioritization strategyExternal biological resourcesExtreme polygenicityExpression specificityAssociated lociSignaling functionsGene setsAssociation studiesNeuronal differentiationFunctional interactionGenesLociBiological resourcesPolygenicityNovel strategyPrioritization strategiesSpecific hypothesesDifferentiationPathwayStatistical powerLarge numberIntegrating human brain proteomes with genome-wide association data implicates novel proteins in post-traumatic stress disorder
Wingo TS, Gerasimov ES, Liu Y, Duong DM, Vattathil SM, Lori A, Gockley J, Breen MS, Maihofer AX, Nievergelt CM, Koenen KC, Levey DF, Gelernter J, Stein MB, Ressler KJ, Bennett DA, Levey AI, Seyfried NT, Wingo AP. Integrating human brain proteomes with genome-wide association data implicates novel proteins in post-traumatic stress disorder. Molecular Psychiatry 2022, 27: 3075-3084. PMID: 35449297, PMCID: PMC9233006, DOI: 10.1038/s41380-022-01544-4.Peer-Reviewed Original ResearchConceptsProteome-wide association studyTranscriptome-wide association studyGenome-wide association studiesBrain protein abundanceHuman brain proteomeBrain proteomeAssociation studiesProtein abundanceGenome-wide association dataHuman brain transcriptomePost-traumatic stress disorderGWAS resultsNovel proteinBrain transcriptomeRisk lociProteomeGenesAssociation dataPrecursor cellsPTSD pathogenesisBrain mRNA levelsMRNA levelsOligodendrocyte precursor cellsPromising targetNew insights
2021
Pleiotropic effects of telomere length loci with brain morphology and brain tissue expression
Pathak GA, Wendt FR, Levey DF, Mecca AP, van Dyck CH, Gelernter J, Polimanti R. Pleiotropic effects of telomere length loci with brain morphology and brain tissue expression. Human Molecular Genetics 2021, 30: 1360-1370. PMID: 33831179, PMCID: PMC8255129, DOI: 10.1093/hmg/ddab102.Peer-Reviewed Original ResearchConceptsMethylation expressionGenetic variantsMapping gene functionTelomere lengthChromatin associationChromatin profilesGene functionGenetic colocalizationGene mappingGenomic relationshipsNeuropsychiatric traitsPleiotropic rolesDrug-gene interactionsCertain lociBrain tissue expressionGenesLociPleiotropic effectsBrain morphology measuresNucleotide polymorphismsAncestry populationsTissue expressionPhenotypic associationsPleiotropyAncestry groups
2020
Characterizing the effect of background selection on the polygenicity of brain-related traits
Wendt FR, Pathak GA, Overstreet C, Tylee DS, Gelernter J, Atkinson EG, Polimanti R. Characterizing the effect of background selection on the polygenicity of brain-related traits. Genomics 2020, 113: 111-119. PMID: 33278486, PMCID: PMC7855394, DOI: 10.1016/j.ygeno.2020.11.032.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesBrain-related traitsGWAS of schizophreniaTrait-associated lociLocus effect sizesSubset of traitsGenotype networksGenetic architectureIntolerant regionsBrain-related phenotypesBackground selectionNatural selectionEvolutionary pressurePositive selectionSNP heritabilityLocal ancestryAssociation studiesTraitsFunctional significanceLociPolygenicityBinary annotationPhenotypeRisk allelesSize variance
2019
Genomewide Gene-by-Sex Interaction Scans Identify ADGRV1 for Sex Differences in Opioid Dependent African Americans
Yang BZ, Zhou H, Cheng Z, Kranzler HR, Gelernter J. Genomewide Gene-by-Sex Interaction Scans Identify ADGRV1 for Sex Differences in Opioid Dependent African Americans. Scientific Reports 2019, 9: 18070. PMID: 31792237, PMCID: PMC6889277, DOI: 10.1038/s41598-019-53560-0.Peer-Reviewed Original ResearchMeSH KeywordsAdultAllelesAnalgesics, OpioidBlack or African AmericanBrainCalcium-Binding ProteinsFemaleGene Expression ProfilingGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMaleMiddle AgedOpioid-Related DisordersPolymorphism, Single NucleotideReceptors, G-Protein-CoupledReceptors, Kainic AcidSex FactorsWhite PeopleConceptsOpioid dependenceOD riskSex-different effectsSex differencesInferior olivary nucleusDSM-IV diagnosisDimorphic riskSubstantia nigraAA menOlivary nucleusFrontal cortexEuropean-American subjectsADGRV1Further studiesRiskAfrican AmericansGenetic variantsDisease enrichment analysisBrainSex interactionNominal significanceMenFirst studyPutamenLung
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
Widespread signatures of positive selection in common risk alleles associated to autism spectrum disorder
Polimanti R, Gelernter J. Widespread signatures of positive selection in common risk alleles associated to autism spectrum disorder. PLOS Genetics 2017, 13: e1006618. PMID: 28187187, PMCID: PMC5328401, DOI: 10.1371/journal.pgen.1006618.Peer-Reviewed Original ResearchMeSH KeywordsAllelesAttention Deficit Disorder with HyperactivityAutism Spectrum DisorderBipolar DisorderBrainComputational BiologyDepressive Disorder, MajorGene Expression ProfilingGene OntologyGene Regulatory NetworksGenetic Predisposition to DiseaseGenome-Wide Association StudyGenomicsHumansPituitary GlandPolymorphism, Single NucleotideRisk FactorsSchizophreniaTranscriptomeConceptsPositive selectionGene Ontology enrichmentGene expression enrichmentPrevious genetic studiesGWAS summary statisticsNervous system developmentCommon risk allelesPsychiatric Genomics ConsortiumSystems geneticsOntology enrichmentRisk allelesSynapse organizationWidespread signaturesEvolutionary processesGenetic studiesGenomics ConsortiumGWASHuman evolutionAllelesIncomplete selectionEffect directionMinor alleleComplete selectionEnrichmentSummary statistics
2016
Effects of ANK3 variation on gray and white matter in bipolar disorder
Lippard ETC, Jensen KP, Wang F, Johnston JAY, Spencer L, Pittman B, Gelernter J, Blumberg HP. Effects of ANK3 variation on gray and white matter in bipolar disorder. Molecular Psychiatry 2016, 22: 1345-1351. PMID: 27240527, PMCID: PMC5133179, DOI: 10.1038/mp.2016.76.Peer-Reviewed Original Research
2015
RDoC and translational perspectives on the genetics of trauma‐related psychiatric disorders
Montalvo-Ortiz JL, Gelernter J, Hudziak J, Kaufman J. RDoC and translational perspectives on the genetics of trauma‐related psychiatric disorders. American Journal Of Medical Genetics Part B Neuropsychiatric Genetics 2015, 171: 81-91. PMID: 26592203, PMCID: PMC4754782, DOI: 10.1002/ajmg.b.32395.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsStress-related psychiatric disordersPsychiatric disordersTrauma-related psychiatric disordersAdverse early life experiencesSubstance use disordersGenetic risk factorsKey brain structuresDistinct neural circuitsDistinct psychiatric disordersSubstance use problemsClinical syndromeRisk factorsHigh riskPsychiatric problemsUse disordersAdverse early experiencesTranslational studiesGenome-wide association studiesClinical phenotypeNeural circuitsBrain structuresResearch Domain Criteria frameworkCircuitry developmentEarly life experiencesAnxiety disordersThe Research Domain Criteria (RDoC) Project and Studies of Risk and Resilience in Maltreated Children
Kaufman J, Gelernter J, Hudziak JJ, Tyrka AR, Coplan JD. The Research Domain Criteria (RDoC) Project and Studies of Risk and Resilience in Maltreated Children. Journal Of The American Academy Of Child & Adolescent Psychiatry 2015, 54: 617-625. PMID: 26210330, PMCID: PMC4515569, DOI: 10.1016/j.jaac.2015.06.001.Peer-Reviewed Original ResearchConceptsResearch Domain Criteria projectNeural circuitsSubset of patientsRelevant animal modelsOnset of psychopathologyStress-related mechanismsClinical studiesStandard interventionAnimal modelsClinical implicationsMental disordersMaltreated childrenNeural circuitryTranslational researchPrecision medicinePsychiatric nomenclaturePatientsChildrenRDoC projectRDoC frameworkNeurobiological measuresRDoC initiativeRiskUltimate long-term goalStudy of risk
2014
The α-endomannosidase gene (MANEA) is associated with panic disorder and social anxiety disorder
Jensen KP, Stein MB, Kranzler HR, Yang BZ, Farrer LA, Gelernter J. The α-endomannosidase gene (MANEA) is associated with panic disorder and social anxiety disorder. Translational Psychiatry 2014, 4: e353-e353. PMID: 24473444, PMCID: PMC3905232, DOI: 10.1038/tp.2013.122.Peer-Reviewed Original ResearchConceptsPanic disorderAnxiety disordersCocaine-induced paranoiaAnxiety disorder casesWhole blood cellsPsychiatric disorder riskWarrants further investigationAfrican American subjectsComorbid drugPD casesPsychiatric disordersAlcohol dependenceBrain tissueCocaine useBehavioral effectsBlood cellsClinical potentialGene variantsDisordersDisorder casesSingle nucleotide polymorphismsDisorder riskIndependent samplesPsychiatric phenotypesFurther investigation
2012
Genetic influences of resting state fMRI activity in language-related brain regions in healthy controls and schizophrenia patients: a pilot study
Jamadar S, Powers NR, Meda SA, Calhoun VD, Gelernter J, Gruen JR, Pearlson GD. Genetic influences of resting state fMRI activity in language-related brain regions in healthy controls and schizophrenia patients: a pilot study. Brain Imaging And Behavior 2012, 7: 15-27. PMID: 22669497, PMCID: PMC4428558, DOI: 10.1007/s11682-012-9168-1.Peer-Reviewed Original Research
2011
The association of genetic variation in CACNA1C with structure and function of a frontotemporal system
Wang F, McIntosh AM, He Y, Gelernter J, Blumberg HP. The association of genetic variation in CACNA1C with structure and function of a frontotemporal system. Bipolar Disorders 2011, 13: 696-700. PMID: 22085483, PMCID: PMC3233238, DOI: 10.1111/j.1399-5618.2011.00963.x.Peer-Reviewed Original ResearchConceptsBipolar disorderFrontotemporal neural systemFunctional connectivityGG groupHigh-resolution structural magnetic resonance imaging scanMagnetic resonance imaging (MRI) scansNeural system effectsStructural magnetic resonance imaging (MRI) scansResonance imaging scansFunctional MRI scansGray matter volumeFunctional connectivity analysisNeural systemsGray matter morphologyCorticolimbic structuresImaging scansHigh riskMatter volumeMRI scansCACNA1C variationNeural circuitryCACNA1C geneSingle nucleotide polymorphismsConnectivity analysisAssociationRare Nonsynonymous Variants in Alpha-4 Nicotinic Acetylcholine Receptor Gene Protect Against Nicotine Dependence
Xie P, Kranzler HR, Krauthammer M, Cosgrove KP, Oslin D, Anton RF, Farrer LA, Picciotto MR, Krystal JH, Zhao H, Gelernter J. Rare Nonsynonymous Variants in Alpha-4 Nicotinic Acetylcholine Receptor Gene Protect Against Nicotine Dependence. Biological Psychiatry 2011, 70: 528-536. PMID: 21683344, PMCID: PMC3199609, DOI: 10.1016/j.biopsych.2011.04.017.Peer-Reviewed Original Research
2010
Genetic Associations of Brain Structural Networks in Schizophrenia: A Preliminary Study
Jagannathan K, Calhoun VD, Gelernter J, Stevens MC, Liu J, Bolognani F, Windemuth A, Ruaño G, Assaf M, Pearlson GD. Genetic Associations of Brain Structural Networks in Schizophrenia: A Preliminary Study. Biological Psychiatry 2010, 68: 657-666. PMID: 20691427, PMCID: PMC2990476, DOI: 10.1016/j.biopsych.2010.06.002.Peer-Reviewed Original ResearchConceptsSpecific structural brain abnormalitiesMagnetic resonance imaging (MRI) scansSmall sample sizeHealthy control subjectsStructural brain abnormalitiesStructural magnetic resonance imaging (MRI) scansGray matter deficitsResonance imaging scansCortical gray matterNormal central nervous system developmentRisk genesCentral nervous system developmentBrain structural networksControl subjectsImaging scansBrain abnormalitiesNervous system developmentIllness markersSchizophrenia pathophysiologySchizophrenia risk genesGenetic componentTemporal lobeBrain areasEuropean-American subjectsSchizophrenia patients