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A genome-wide investigation into the underlying genetic architecture of personality traits and overlap with psychopathology
Gupta P, Galimberti M, Liu Y, Beck S, Wingo A, Wingo T, Adhikari K, Kranzler H, Stein M, Gelernter J, Levey D. A genome-wide investigation into the underlying genetic architecture of personality traits and overlap with psychopathology. Nature Human Behaviour 2024, 8: 2235-2249. PMID: 39134740, PMCID: PMC11576509, DOI: 10.1038/s41562-024-01951-3.Peer-Reviewed Original ResearchPersonality traitsPsychiatric traitsBidirectional effectsGenetic architectureHuman personality traitsGenetic correlation analysisGene-based association testsGenome-wide significant lociNeuroticismAgreeablenessGenome-wide association studiesGenome-wide association study meta-analysisMental illnessGenome-wide investigationAssociation TestComplex human traitsProteome-wide analysisAnxietyDepressionExtraversionConscientiousnessExpression of genesNovel lociSignificant lociTranscriptome-wideMulti-ancestry genome-wide association study of cannabis use disorder yields insight into disease biology and public health implications
Levey D, Galimberti M, Deak J, Wendt F, Bhattacharya A, Koller D, Harrington K, Quaden R, Johnson E, Gupta P, Biradar M, Lam M, Cooke M, Rajagopal V, Empke S, Zhou H, Nunez Y, Kranzler H, Edenberg H, Agrawal A, Smoller J, Lencz T, Hougaard D, Børglum A, Demontis D, Gaziano J, Gandal M, Polimanti R, Stein M, Gelernter J. Multi-ancestry genome-wide association study of cannabis use disorder yields insight into disease biology and public health implications. Nature Genetics 2023, 55: 2094-2103. PMID: 37985822, PMCID: PMC10703690, DOI: 10.1038/s41588-023-01563-z.Peer-Reviewed Original ResearchConceptsSingle nucleotide polymorphism-based heritabilityMulti-ancestry genome-wide association studyAssociation studiesMillion Veteran ProgramGenome-wide association studiesWide significant lociWide association studySignificant lociReference panelSmall populationDisease biologyAncestryAmerican ancestryHeritabilityVeteran ProgramNumerous medical comorbiditiesLung cancer riskRelationship analysisLociBiologyPublic health implicationsEast AsiansPublic health consequencesMedical comorbiditiesCigarette smokingBi-ancestral depression GWAS in the Million Veteran Program and meta-analysis in >1.2 million individuals highlight new therapeutic directions
Levey DF, Stein MB, Wendt FR, Pathak GA, Zhou H, Aslan M, Quaden R, Harrington KM, Nuñez YZ, Overstreet C, Radhakrishnan K, Sanacora G, McIntosh AM, Shi J, Shringarpure SS, Concato J, Polimanti R, Gelernter J. Bi-ancestral depression GWAS in the Million Veteran Program and meta-analysis in >1.2 million individuals highlight new therapeutic directions. Nature Neuroscience 2021, 24: 954-963. PMID: 34045744, PMCID: PMC8404304, DOI: 10.1038/s41593-021-00860-2.Peer-Reviewed Original ResearchConceptsTranscriptome-wide association studyMillion Veteran ProgramTranscriptome-wide association study (TWAS) analysisGenomic risk lociComplex psychiatric traitsGenetic architectureRisk lociGene expressionAssociation studiesLikely pathogenicityPsychiatric traitsVeteran ProgramNew therapeutic directionEuropean ancestryNew insightsAncestryUK BiobankAfrican ancestrySubstantial replicationExpressionLarge independent cohortsGWASTherapeutic directionsGenesLociReproducible 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 GWASsGenetic 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 stressA contextual genomic perspective on physical activity and its relationship to health, well being and illness
Galimberti M, Levey D, Deak J, Adhikari K, Overstreet C, Gupta P, Nitin R, Zhou H, Lake N, Harrington K, Djousse L, Davis L, Gaziano J, Stein M, Gelernter J. A contextual genomic perspective on physical activity and its relationship to health, well being and illness. Nature Genetics 2025, 57: 1860-1871. PMID: 40691405, PMCID: PMC12339386, DOI: 10.1038/s41588-025-02260-9.Peer-Reviewed Original ResearchConceptsLeisure-time PAPhysical activityLeisure-timeHealth benefitsIndividuals of European ancestryMendelian randomization analysisMillion Veteran ProgramUK Biobank dataLatin American ancestryHealth outcomesVeteran ProgramRandomization analysisBiobank dataRespiratory system diseasesLead variantsCOVID-19 hospitalizationCross-ancestryEuropean ancestryHealthMeta-analysisGenetic analysisAmerican ancestryAfrican ancestryCross-ancestry meta-analysisMetabolic traits
2026
Genomic Study of Resilience to Posttraumatic Stress Disorder in the Million Veteran Program
Overstreet C, Levey D, Adhikari K, Galimberti M, Pathak G, Pietrzak R, Zhou H, Løkhammer S, Polimanti R, Harrington K, Quaden R, Amstadter A, Gaziano J, Stein M, Gelernter J, Muralidhar S, Moser J, Deen J, Tsao P, Gaziano J, Hauser E, Kilbourne A, Matheny M, Oslin D, Voora D, Gaziano J, Tsao P, Brewer J, Brophy M, Cho K, Churby L, DuVall S, Pyarajan S, Ringer R, Selva L, Shayan S, Stephens B, Whitbourne S, Assimes T, Hung A, Kranzler H. Genomic Study of Resilience to Posttraumatic Stress Disorder in the Million Veteran Program. Biological Psychiatry 2026 PMID: 41763442, DOI: 10.1016/j.biopsych.2026.01.022.Peer-Reviewed Original ResearchPosttraumatic stress disorderTranscriptome-wide association studyMillion Veteran ProgramGenome-wide association studiesStress disorderCombat exposureEuropean ancestryPosttraumatic stress disorder symptomsSignificant lociFine-mappingVeteran ProgramGenomic studiesAssociation studiesAfrican ancestryTrans-ancestry meta-analysisGenome-wide significant lociSNP-based heritabilityStudy of resiliencePsychiatric resiliencePsychiatric symptomsNo significant lociPCL-17Resilience measuresTrans-ancestryDisordersCannabis use, cognitive function and dementia risk in older adults: observational and genetic analyses
Ishrat S, Levey D, Gelernter J, Ebmeier K, Topiwala A. Cannabis use, cognitive function and dementia risk in older adults: observational and genetic analyses. BMJ Mental Health 2026, 29: e302290. PMID: 41741130, PMCID: PMC12958891, DOI: 10.1136/bmjment-2025-302290.Peer-Reviewed Original ResearchMillion Veteran ProgramDementia riskOlder adultsMR analysisMendelian randomisationCannabis useIncident all-cause dementiaAssociated with dementia riskCognitive performanceAll-cause dementiaCannabis usersCognitive agingCognitive effectsCognitive declineCognitive functionLongitudinal cognitive performanceEffects of cannabis useCox proportional hazards modelsCannabis use disorderPotential causal relationshipProportional hazards modelLongitudinal cognitive declineVeteran ProgramCognitive screeningLifetime cannabis usersGenome-wide association study of major anxiety disorders in 122,341 European-ancestry cases identifies 58 loci and highlights GABAergic signaling
Strom N, Verhulst B, Bacanu S, Cheesman R, Purves K, Gedik H, Mitchell B, Kwong A, Faucon A, Singh K, Medland S, Colodro-Conde L, Krebs K, Hoffmann P, Herms S, Gehlen J, Ripke S, Awasthi S, Palviainen T, Tasanko E, Peterson R, Adkins D, Shabalin A, Adams M, Iveson M, Campbell A, Thomas L, Winsvold B, Drange O, Børte S, ter Kuile A, Naamanka J, Nguyen T, Meier S, Corfield E, Hannigan L, Levey D, Czamara D, Weber H, Choi K, Pistis G, Couvy-Duchesne B, Van der Auwera S, Teumer A, Karlsson R, Garcia-Argibay M, Lee D, Wang R, Bjerkeset O, Stordal E, Bäckman J, Salum G, Zai C, Kennedy J, Zai G, Tiwari A, Heilmann-Heimbach S, Schmidt B, Kaprio J, Kennedy M, Boden J, Havdahl A, Middeldorp C, Lopes F, Akula N, McMahon F, Binder E, Fehm L, Ströhle A, Castelao E, Tiemeier H, Stein D, Whiteman D, Olsen C, Fuller Z, Wang X, Wray N, Byrne E, Lewis G, Timpson N, Davis L, Hickie I, Gillespie N, Milani L, Schumacher J, Woldbye D, Forstner A, Nöthen M, Hovatta I, Horwood J, Copeland W, Maes H, McIntosh A, Andreassen O, Zwart J, Mors O, Børglum A, Mortensen P, Ask H, Reichborn-Kjennerud T, Najman J, Stein M, Gelernter J, Milaneschi Y, Penninx B, Boomsma D, Maron E, Erhardt-Lehmann A, Rück C, Kircher T, Melzig C, Alpers G, Arolt V, Domschke K, Smoller J, Preisig M, Martin N, Lupton M, Luik A, Reif A, Grabe H, Larsson H, Magnusson P, Oldehinkel A, Hartman C, Breen G, Docherty A, Coon H, Conrad R, Lehto K, Deckert J, Eley T, Mattheisen M, Hettema J. Genome-wide association study of major anxiety disorders in 122,341 European-ancestry cases identifies 58 loci and highlights GABAergic signaling. Nature Genetics 2026, 58: 275-288. PMID: 41634414, PMCID: PMC12900644, DOI: 10.1038/s41588-025-02485-8.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesAnxiety disordersGABAergic signalingGenome-wide significant risk variantsGenetic architectureThreat response systemsFunctional follow-up studiesGenome-wide association meta-analysisFollow-up analysisAssociation meta-analysisBrain regionsTwin studiesInternal phenotypesRisk variantsGenetic riskEuropean-ancestry casesEuropean ancestryANXGlobal disabilityFollow-up studyDisordersGenetic correlationsClinical presentationGenesFollow-up
Academic Achievements & Community Involvement
News
News
- December 02, 2025Source: Nature Communications
Multi-Ancestry Investigation of the Genomics of Erectile Dysfunction
- September 24, 2025Source: BMJ Evidence-Based Medicine
Alcohol Use and Risk of Dementia in Diverse Populations: Evidence from Cohort, Case–Control and Mendelian Randomisation Approaches
- September 24, 2025
New Study Reveals Genetic, Psychiatric, and Environmental Factors Contributing to Alcohol Use Disorder
- July 21, 2025
Yale Study: Physical Activity and its Relationship to Health, Well-Being, and Illness