Featured Publications
Genetic associations with suicide attempt severity and genetic overlap with major depression
Levey DF, Polimanti R, Cheng Z, Zhou H, Nuñez YZ, Jain S, He F, Sun X, Ursano RJ, Kessler RC, Smoller JW, Stein MB, Kranzler HR, Gelernter J. Genetic associations with suicide attempt severity and genetic overlap with major depression. Translational Psychiatry 2019, 9: 22. PMID: 30655502, PMCID: PMC6336846, DOI: 10.1038/s41398-018-0340-2.Peer-Reviewed Original ResearchConceptsGWS associationsGenome-wide significant signalsCircadian clock regulationWide association studyGenetic overlapCatabolism of tyrosineClock regulationFirst GWASSignificant genetic overlapDiscovery GWASChromosome 12Large GWASMolecular mechanismsAssociation studiesChromosome 15Chromosome 18Genetic influencesDiscovery sampleGenetic associationSuicide attempt severityReplication analysisGWASAnaerobic energy productionGenetic risk factorsPolygenic risk scoresTowards understanding and predicting suicidality in women: biomarkers and clinical risk assessment
Levey DF, Niculescu EM, Le-Niculescu H, Dainton HL, Phalen PL, Ladd TB, Weber H, Belanger E, Graham DL, Khan FN, Vanipenta NP, Stage EC, Ballew A, Yard M, Gelbart T, Shekhar A, Schork NJ, Kurian SM, Sandusky GE, Salomon DR, Niculescu AB. Towards understanding and predicting suicidality in women: biomarkers and clinical risk assessment. Molecular Psychiatry 2016, 21: 768-785. PMID: 27046645, DOI: 10.1038/mp.2016.31.Peer-Reviewed Original ResearchConceptsFuture hospitalizationConvergent functional genomics approachSuicide completersPrimary end pointSingle blood biomarkerTop biomarkersReceiver-operating characteristic areaRisk prediction scoreClinical risk assessmentDisorder participantsIndependent test cohortForm of APPProphylactic benefitNeurotrophic effectsBlood biomarkersSleep abnormalitiesPsychiatric hospitalizationHospitalizationMood disordersTest cohortCandidate biomarkersSuicide completionSuicidal ideationDrug lithiumChronic stress
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 MGAssociation 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 Research
2023
Genome-wide association studies and cross-population meta-analyses investigating short and long sleep duration
Austin-Zimmerman I, Levey D, Giannakopoulou O, Deak J, Galimberti M, Adhikari K, Zhou H, Denaxas S, Irizar H, Kuchenbaecker K, McQuillin A, Concato J, Buysse D, Gaziano J, Gottlieb D, Polimanti R, Stein M, Bramon E, Gelernter J. Genome-wide association studies and cross-population meta-analyses investigating short and long sleep duration. Nature Communications 2023, 14: 6059. PMID: 37770476, PMCID: PMC10539313, DOI: 10.1038/s41467-023-41249-y.Peer-Reviewed Original ResearchConceptsAssociation studiesGenome-wide association studiesGenetic correlationsWide association studyLinkage disequilibrium scorePositive genetic correlationSleep traitsIndependent lociMillion Veteran ProgramTraitsAncestryUK BiobankVeteran ProgramMendelian randomisationLociHeritabilitySNPsPhenotypeEast AsiansSimilar patternCardiometabolic phenotypes
2019
Genome-wide association study of post-traumatic stress disorder reexperiencing symptoms in >165,000 US veterans
Gelernter J, Sun N, Polimanti R, Pietrzak R, Levey DF, Bryois J, Lu Q, Hu Y, Li B, Radhakrishnan K, Aslan M, Cheung KH, Li Y, Rajeevan N, Sayward F, Harrington K, Chen Q, Cho K, Pyarajan S, Sullivan PF, Quaden R, Shi Y, Hunter-Zinck H, Gaziano JM, Concato J, Zhao H, Stein MB. Genome-wide association study of post-traumatic stress disorder reexperiencing symptoms in >165,000 US veterans. Nature Neuroscience 2019, 22: 1394-1401. PMID: 31358989, PMCID: PMC6953633, DOI: 10.1038/s41593-019-0447-7.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesAssociation studiesHigh linkage disequilibrium regionLinkage disequilibrium regionWide association studyDisequilibrium regionBioinformatics analysisTranscriptomic profilesMillion Veteran ProgramChromosome 17Genetic risk factorsNew insightsUK Biobank dataReexperiencing of traumaStriatal medium spiny neuronsVeteran ProgramSignificant regionsCAMKVEuropean AmericansBiobank dataMedium spiny neuronsTCF4BiologyKANSL1African American cohortGenome-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
2017
Precision medicine for suicidality: from universality to subtypes and personalization
Niculescu A, Le-Niculescu H, Levey D, Phalen P, Dainton H, Roseberry K, Niculescu E, Niezer J, Williams A, Graham D, Jones T, Venugopal V, Ballew A, Yard M, Gelbart T, Kurian S, Shekhar A, Schork N, Sandusky G, Salomon D. Precision medicine for suicidality: from universality to subtypes and personalization. Molecular Psychiatry 2017, 22: 1250-1273. PMID: 28809398, PMCID: PMC5582166, DOI: 10.1038/mp.2017.128.Peer-Reviewed Original ResearchConceptsSuicidal ideationIndependent cohortPersonalized approachFuture hospitalizationPsychiatric diagnosisCandidate biomarkersUniversal biomarkerBlood gene expression biomarkersBiology of suicideTop biomarkersNovel predictive biomarkerHigh-risk groupNon-psychiatric disordersDrug repurposing analysisPublic health problemMonitoring of responseNovel potential therapeuticsHigher suicidal ideationPredictive biomarkersClinical trialsComprehensive stepwise approachRisk groupsLarge cohortMood disordersPreventive therapeutics
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
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 mice
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