Featured Publications
Reproducible Genetic Risk Loci for Anxiety: Results From ∼200,000 Participants in the Million Veteran Program
Levey DF, Gelernter J, Polimanti R, Zhou H, Cheng Z, Aslan M, Quaden R, Concato J, Radhakrishnan K, Bryois J, Sullivan PF, Stein M. Reproducible Genetic Risk Loci for Anxiety: Results From ∼200,000 Participants in the Million Veteran Program. American Journal Of Psychiatry 2020, 177: 223-232. PMID: 31906708, PMCID: PMC7869502, DOI: 10.1176/appi.ajp.2019.19030256.Peer-Reviewed Original ResearchConceptsNovel genome-wide significant associationsGene expressionGenome-wide significant signalsGenome-wide significant associationMillion Veteran ProgramWide association studyGenetic risk lociSignificant genetic correlationsGenetic risk mechanismsGenetic architectureGlobal regulatorChromosome 3Risk lociChromosome 6Chromosome 7Association studiesLargest GWASLarge biobanksGlobal regulationGenetic correlationsContinuous traitsVeteran ProgramGWASsLociPrevious GWASs
2024
Genome-wide meta-analysis of myasthenia gravis uncovers new loci and provides insights into polygenic prediction
Braun A, Shekhar S, Levey D, Straub P, Kraft J, Panagiotaropoulou G, Heilbron K, Awasthi S, Meleka Hanna R, Hoffmann S, Stein M, Lehnerer S, Mergenthaler P, Elnahas A, Topaloudi A, Koromina M, Palviainen T, Asbjornsdottir B, Stefansson H, Skuladóttir A, Jónsdóttir I, Stefansson K, Reis K, Esko T, Palotie A, Leypoldt F, Stein M, Fontanillas P, Kaprio J, Gelernter J, Davis L, Paschou P, Tannemaat M, Verschuuren J, Kuhlenbäumer G, Gregersen P, Huijbers M, Stascheit F, Meisel A, Ripke S. Genome-wide meta-analysis of myasthenia gravis uncovers new loci and provides insights into polygenic prediction. Nature Communications 2024, 15: 9839. PMID: 39537604, PMCID: PMC11560923, DOI: 10.1038/s41467-024-53595-6.Peer-Reviewed Original ResearchConceptsPerformance of polygenic risk scoresGenome-wide significant hitsGenome-wide association studiesGenome-wide meta-analysisControls of European ancestryGenetic architecturePolygenic risk scoresSignificant hitsAssociation studiesPhenotypic variationPolygenic predictionEuropean ancestryAssociated with early-onsetHuman leukocyte antigen allelesLociEarly-onsetReplication studyNeuromuscular junctionMyasthenia gravisAutoantibody-mediated diseasesAntigen allelesAllelesAncestryDisease manifestationsLate-onset MGGenome-wide association study of the common retinal disorder epiretinal membrane: Significant risk loci in each of three American populations
Gelernter J, Levey D, Galimberti M, Harrington K, Zhou H, Adhikari K, Gupta P, Program V, Gaziano J, Eliott D, Stein M. Genome-wide association study of the common retinal disorder epiretinal membrane: Significant risk loci in each of three American populations. Cell Genomics 2024, 4: 100582. PMID: 38870908, PMCID: PMC11228954, DOI: 10.1016/j.xgen.2024.100582.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesMillion Veteran ProgramRisk lociAssociation studiesTrans-ancestry meta-analysisSignificant risk lociPathway enrichment analysisEpiretinal membraneTrans-ancestryGenome-wideMultiple traitsGenetic associationEnrichment analysisGene expressionEuropean AmericansLoss of visual acuityVeteran ProgramGenetic correlationsLociBiological mechanismsAmerican populationVisual acuityRetinal conditionsControl individualsRetinal surfaceAssociation between psoriasis and obsessive-compulsive disorder: a case-control study in the All of Us research program
Craver A, Chen G, Fan R, Levey D, Cohen J. Association between psoriasis and obsessive-compulsive disorder: a case-control study in the All of Us research program. Archives Of Dermatological Research 2024, 316: 280. PMID: 38796663, DOI: 10.1007/s00403-024-03112-y.Peer-Reviewed Original ResearchAssociation 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
Associations 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 function
2019
Apolipoprotein E gene polymorphism, posttraumatic stress disorder, and cognitive function in older U.S. veterans: Results from the National Health and Resilience in Veterans Study
Averill LA, Abdallah CG, Levey DF, Han S, Harpaz‐Rotem I, Kranzler HR, Southwick SM, Krystal JH, Gelernter J, Pietrzak RH. Apolipoprotein E gene polymorphism, posttraumatic stress disorder, and cognitive function in older U.S. veterans: Results from the National Health and Resilience in Veterans Study. Depression And Anxiety 2019, 36: 834-845. PMID: 31385647, DOI: 10.1002/da.22912.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderExecutive functionCognitive functioningStress disorderΕ4 carrier statusΕ4 carriersVeterans StudyCognitive dysfunctionAttention/concentrationGreater cognitive difficultiesLower cognitive functioningOlder U.S. veteransΕ4 allele carrier statusPerseverative errorsCognitive difficultiesReplication sampleCarrier statusCognitive functionImportance of assessingNational HealthCognitive declinePredictive effectApolipoprotein E gene polymorphismE gene polymorphismΕ4 allele carriersGenome-wide Association Study of Maximum Habitual Alcohol Intake in >140,000 U.S. European and African American Veterans Yields Novel Risk Loci
Gelernter J, Sun N, Polimanti R, Pietrzak RH, Levey DF, Lu Q, Hu Y, Li B, Radhakrishnan K, Aslan M, Cheung KH, Li Y, Rajeevan N, Sayward F, Harrington K, Chen Q, Cho K, Honerlaw J, Pyarajan S, Lencz T, Quaden R, Shi Y, Hunter-Zinck H, Gaziano JM, Kranzler HR, Concato J, Zhao H, Stein MB, Program D, Program M. Genome-wide Association Study of Maximum Habitual Alcohol Intake in >140,000 U.S. European and African American Veterans Yields Novel Risk Loci. Biological Psychiatry 2019, 86: 365-376. PMID: 31151762, PMCID: PMC6919570, DOI: 10.1016/j.biopsych.2019.03.984.Peer-Reviewed Original ResearchConceptsAdditional genome-wide significant lociRisk lociWide association study (GWAS) analysisAssociation studiesGenome-wide significant lociGenome-wide association studiesGenetic correlationsWide association studyNovel risk lociAlcohol-related traitsStrong statistical supportSmoking-related traitsAdditional genomesSignificant lociPancreatic delta cellsChromosome 4Chromosome 11Protein productsChromosome 8Quantitative phenotypesMillion Veteran ProgramVeterans Affairs Million Veteran ProgramLociCell typesChromosome 17Towards precision medicine for stress disorders: diagnostic biomarkers and targeted drugs
Le-Niculescu H, Roseberry K, Levey D, Rogers J, Kosary K, Prabha S, Jones T, Judd S, McCormick M, Wessel A, Williams A, Phalen P, Mamdani F, Sequeira A, Kurian S, Niculescu A. Towards precision medicine for stress disorders: diagnostic biomarkers and targeted drugs. Molecular Psychiatry 2019, 25: 918-938. PMID: 30862937, PMCID: PMC7192849, DOI: 10.1038/s41380-019-0370-z.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAdultBeta 2-MicroglobulinBiomarkersDEAD-box RNA HelicasesFemaleGene ExpressionHumansMaleMental DisordersMiddle AgedMolecular Targeted TherapyNogo ProteinsPrecision MedicinePredictive Value of TestsProto-Oncogene ProteinsReceptors, ImmunologicStress, PsychologicalTacrolimus Binding ProteinsTelomere HomeostasisConceptsPredictive biomarkersGene expression biomarkersTelomere lengthBlood gene expression biomarkersPossible new drug candidateStress disorderPsychological stressFuture psychiatric hospitalizationsVisual analog scaleHigh-risk groupSimple visual analog scaleDrug repurposing analysisExpression biomarkersGene expression signaturesAnalog scaleAdverse outcomesCalcium folinateCohort designHormonal changesPsychiatric hospitalizationDecreased qualityBiomarker findingsPsychiatric disordersPsychiatric patientsPatient stratificationTowards precision medicine for pain: diagnostic biomarkers and repurposed drugs
Niculescu A, Le-Niculescu H, Levey D, Roseberry K, Soe K, Rogers J, Khan F, Jones T, Judd S, McCormick M, Wessel A, Williams A, Kurian S, White F. Towards precision medicine for pain: diagnostic biomarkers and repurposed drugs. Molecular Psychiatry 2019, 24: 501-522. PMID: 30755720, PMCID: PMC6477790, DOI: 10.1038/s41380-018-0345-5.Peer-Reviewed Original ResearchConceptsBlood gene expression biomarkersPossible new drug candidateFuture emergency department (ED) visitsEmergency department visitsHigh-risk groupDrug repurposing analysisCurrent opioid epidemicPerception of painSubjects longitudinal designGene expression signaturesPain statesDepartment visitsPain disordersTreatment dilemmaBlood biomarkersSC-560Opioid epidemicCohort designRisk groupsIndependent cohortPainGene expression biomarkersPsychiatric patientsDiagnostic biomarkersIndividual biomarkers
2015
Understanding and predicting suicidality using a combined genomic and clinical risk assessment approach
Niculescu AB, Levey DF, Phalen PL, Le-Niculescu H, Dainton HD, Jain N, Belanger E, James A, George S, Weber H, Graham DL, Schweitzer R, Ladd TB, Learman R, Niculescu EM, Vanipenta NP, Khan FN, Mullen J, Shankar G, Cook S, Humbert C, Ballew A, Yard M, Gelbart T, Shekhar A, Schork NJ, Kurian SM, Sandusky GE, Salomon DR. Understanding and predicting suicidality using a combined genomic and clinical risk assessment approach. Molecular Psychiatry 2015, 20: 1266-1285. PMID: 26283638, PMCID: PMC4759104, DOI: 10.1038/mp.2015.112.Peer-Reviewed Original ResearchConceptsFuture hospitalizationPsychiatric diagnosisSuicidal ideationCandidate biomarkersBipolar disorderPsychiatric participantsBlood gene expression biomarkersSuicidal behaviorConvergent functional genomics approachSuicide completersPreventive lifestyle modificationsTop candidate biomarkersTop biomarkersAcute panic attacksPotential therapeutic targetBipolar disorder participantsMajor psychiatric disordersIndependent test cohortSuicide risk factorsThoughts of suicideLifestyle modificationAcute suicidalityRisk factorsInflammatory responsePsychological stress responses
2013
Discovery and validation of blood biomarkers for suicidality
Le-Niculescu H, Levey DF, Ayalew M, Palmer L, Gavrin LM, Jain N, Winiger E, Bhosrekar S, Shankar G, Radel M, Bellanger E, Duckworth H, Olesek K, Vergo J, Schweitzer R, Yard M, Ballew A, Shekhar A, Sandusky GE, Schork NJ, Kurian SM, Salomon DR, Niculescu AB. Discovery and validation of blood biomarkers for suicidality. Molecular Psychiatry 2013, 18: 1249-1264. PMID: 23958961, PMCID: PMC3835939, DOI: 10.1038/mp.2013.95.Peer-Reviewed Original ResearchMeSH KeywordsAcetyltransferasesAdultAgedBiomarkersBipolar DisorderGene ExpressionGene Expression ProfilingGenomicsHumansIntracellular Signaling Peptides and ProteinsMaleMAP Kinase Kinase Kinase 3Membrane ProteinsMiddle AgedMyristoylated Alanine-Rich C Kinase SubstrateOligonucleotide Array Sequence AnalysisPsychotic DisordersPTEN PhosphohydrolaseSuicidal IdeationSuicideConceptsBlood biomarkersMood disordersBlood gene expression biomarkersConvergent functional genomics approachCase-case designVisual analog scaleHigh-risk populationSimple visual analog scaleBlood expression levelsAge-matched cohortCause of deathMajor mood disordersBlood of subjectsBonferroni correctionExpression levelsBipolar disorder subjectsPsychosis subjectsBlood levelsFuture hospitalizationTime of testingMedication targetsPast hospitalizationHospitalization dataBipolar cohortCompleter group