Featured Publications
Multi-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 smokingGenome-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 phenotypesMulti-ancestry study of the genetics of problematic alcohol use in over 1 million individuals
Zhou H, Kember R, Deak J, Xu H, Toikumo S, Yuan K, Lind P, Farajzadeh L, Wang L, Hatoum A, Johnson J, Lee H, Mallard T, Xu J, Johnston K, Johnson E, Nielsen T, Galimberti M, Dao C, Levey D, Overstreet C, Byrne E, Gillespie N, Gordon S, Hickie I, Whitfield J, Xu K, Zhao H, Huckins L, Davis L, Sanchez-Roige S, Madden P, Heath A, Medland S, Martin N, Ge T, Smoller J, Hougaard D, Børglum A, Demontis D, Krystal J, Gaziano J, Edenberg H, Agrawal A, Justice A, Stein M, Kranzler H, Gelernter J. Multi-ancestry study of the genetics of problematic alcohol use in over 1 million individuals. Nature Medicine 2023, 29: 3184-3192. PMID: 38062264, PMCID: PMC10719093, DOI: 10.1038/s41591-023-02653-5.Peer-Reviewed Original ResearchGenetics 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 ResearchGenome-wide association study in individuals of European and African ancestry and multi-trait analysis of opioid use disorder identifies 19 independent genome-wide significant risk loci
Deak JD, Zhou H, Galimberti M, Levey DF, Wendt FR, Sanchez-Roige S, Hatoum AS, Johnson EC, Nunez YZ, Demontis D, Børglum AD, Rajagopal VM, Jennings MV, Kember RL, Justice AC, Edenberg HJ, Agrawal A, Polimanti R, Kranzler HR, Gelernter J. Genome-wide association study in individuals of European and African ancestry and multi-trait analysis of opioid use disorder identifies 19 independent genome-wide significant risk loci. Molecular Psychiatry 2022, 27: 3970-3979. PMID: 35879402, PMCID: PMC9718667, DOI: 10.1038/s41380-022-01709-1.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesGenome-wide significant risk lociAssociation studiesVariant associationsLarge-scale genome-wide association studiesGenetic correlationsSignificant risk lociPsychiatric Genomics ConsortiumMulti-trait analysisPolygenic risk score analysisSingle-variant associationsGWS lociGenetic architectureIndividuals of EuropeanGWS associationsRisk lociGene regionGenomics ConsortiumMillion Veteran ProgramSusceptibility lociAfrican ancestryLociRisk score analysisGenetic informativenessSNPs oneBi-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 directionsGenesLociGenome-wide association analyses of post-traumatic stress disorder and its symptom subdomains in the Million Veteran Program
Stein MB, Levey DF, Cheng Z, Wendt FR, Harrington K, Pathak GA, Cho K, Quaden R, Radhakrishnan K, Girgenti MJ, Ho YA, Posner D, Aslan M, Duman RS, Zhao H, Polimanti R, Concato J, Gelernter J. Genome-wide association analyses of post-traumatic stress disorder and its symptom subdomains in the Million Veteran Program. Nature Genetics 2021, 53: 174-184. PMID: 33510476, PMCID: PMC7972521, DOI: 10.1038/s41588-020-00767-x.Peer-Reviewed Original ResearchConceptsGenome-wide association analysisAssociation analysisMillion Veteran ProgramGenomic structural equation modelingSignificant lociGenetic varianceGene expressionDrug repositioning candidatesBiological coherenceVeteran ProgramMultiple testing correctionSymptom phenotypeLociRepositioning candidatesAfrican ancestryHeritabilityPhenotypeAncestryExpressionPTSD symptom factorsRegionSubdomainsEnrichmentGenome-wide meta-analysis of problematic alcohol use in 435,563 individuals yields insights into biology and relationships with other traits
Zhou H, Sealock JM, Sanchez-Roige S, Clarke TK, Levey DF, Cheng Z, Li B, Polimanti R, Kember RL, Smith RV, Thygesen JH, Morgan MY, Atkinson SR, Thursz MR, Nyegaard M, Mattheisen M, Børglum AD, Johnson EC, Justice AC, Palmer AA, McQuillin A, Davis LK, Edenberg HJ, Agrawal A, Kranzler HR, Gelernter J. Genome-wide meta-analysis of problematic alcohol use in 435,563 individuals yields insights into biology and relationships with other traits. Nature Neuroscience 2020, 23: 809-818. PMID: 32451486, PMCID: PMC7485556, DOI: 10.1038/s41593-020-0643-5.Peer-Reviewed Original ResearchConceptsRegulatory genomic regionsGenome-wide association studiesNovel risk lociEuropean ancestry individualsPolygenic risk score analysisIndependent risk variantsGenetic architectureGenomic regionsRisk lociAssociation studiesGenetic relationshipsRisk genesGenetic correlationsPsychiatric traitsRisk variantsRisk score analysisTraitsGenetic heritabilityYields insightsBiobank samplesMendelian randomizationGenesLociBiologyHeritabilityGenome-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 alcohol consumption and use disorder in 274,424 individuals from multiple populations
Kranzler HR, Zhou H, Kember RL, Vickers Smith R, Justice AC, Damrauer S, Tsao PS, Klarin D, Baras A, Reid J, Overton J, Rader DJ, Cheng Z, Tate JP, Becker WC, Concato J, Xu K, Polimanti R, Zhao H, Gelernter J. Genome-wide association study of alcohol consumption and use disorder in 274,424 individuals from multiple populations. Nature Communications 2019, 10: 1499. PMID: 30940813, PMCID: PMC6445072, DOI: 10.1038/s41467-019-09480-8.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesAssociation studiesMillion Veteran Program sampleGenetic correlationsWide significant lociSignificant genetic correlationsPolygenic risk scoresCell type groupSignificant lociHeritable traitEnrichment analysisTraitsMultiple populationsLociPhenotypeProgram samplesUnderstanding the comorbidity between posttraumatic stress severity and coronary artery disease using genome-wide information and electronic health records
Polimanti R, Wendt FR, Pathak GA, Tylee DS, Tcheandjieu C, Hilliard AT, Levey DF, Adhikari K, Gaziano JM, O’Donnell C, Assimes TL, Stein MB, Gelernter J. Understanding the comorbidity between posttraumatic stress severity and coronary artery disease using genome-wide information and electronic health records. Molecular Psychiatry 2022, 27: 3961-3969. PMID: 35986173, PMCID: PMC10986859, DOI: 10.1038/s41380-022-01735-z.Peer-Reviewed Original ResearchConceptsCoronary artery diseasePosttraumatic stress disorderElectronic health recordsMillion Veteran ProgramArtery diseaseTotal scoreCAD diagnosisPlatelet amyloid precursor proteinHealth recordsPosttraumatic stress severityAmyloid precursor proteinEarly CAD diagnosisUK BiobankBidirectional relationshipTwo-sample Mendelian randomization (MR) analysisMendelian randomization analysisCAD riskHigh morbidityPTSD symptom severityCARDIoGRAMplusC4D consortiumPleiotropic mechanismsSymptom severityLongitudinal changesDiscordant effectsStress disorderMulti-ancestry genome-wide association study of major depression aids locus discovery, fine mapping, gene prioritization and causal inference
Meng X, Navoly G, Giannakopoulou O, Levey D, Koller D, Pathak G, Koen N, Lin K, Adams M, Rentería M, Feng Y, Gaziano J, Stein D, Zar H, Campbell M, van Heel D, Trivedi B, Finer S, McQuillin A, Bass N, Chundru V, Martin H, Huang Q, Valkovskaya M, Chu C, Kanjira S, Kuo P, Chen H, Tsai S, Liu Y, Kendler K, Peterson R, Cai N, Fang Y, Sen S, Scott L, Burmeister M, Loos R, Preuss M, Actkins K, Davis L, Uddin M, Wani A, Wildman D, Aiello A, Ursano R, Kessler R, Kanai M, Okada Y, Sakaue S, Rabinowitz J, Maher B, Uhl G, Eaton W, Cruz-Fuentes C, Martinez-Levy G, Campos A, Millwood I, Chen Z, Li L, Wassertheil-Smoller S, Jiang Y, Tian C, Martin N, Mitchell B, Byrne E, Awasthi S, Coleman J, Ripke S, Sofer T, Walters R, McIntosh A, Polimanti R, Dunn E, Stein M, Gelernter J, Lewis C, Kuchenbaecker K. Multi-ancestry genome-wide association study of major depression aids locus discovery, fine mapping, gene prioritization and causal inference. Nature Genetics 2024, 56: 222-233. PMID: 38177345, PMCID: PMC10864182, DOI: 10.1038/s41588-023-01596-4.Peer-Reviewed Original Research
2024
Cross-ancestry genetic investigation of schizophrenia, cannabis use disorder, and tobacco smoking
Johnson E, Austin-Zimmerman I, Thorpe H, Levey D, Baranger D, Colbert S, Demontis D, Khokhar J, Davis L, Edenberg H, Di Forti M, Sanchez-Roige S, Gelernter J, Agrawal A. Cross-ancestry genetic investigation of schizophrenia, cannabis use disorder, and tobacco smoking. Neuropsychopharmacology 2024, 1-11. PMID: 38906991, DOI: 10.1038/s41386-024-01886-3.Peer-Reviewed Original ResearchCannabis use disorderUse disorderPleiotropic lociCo-occurring substance useHeavy cannabis useInvestigation of schizophreniaSubstance use disordersGenome-wide studiesGenetic factorsMental health conditionsExecutive functionCannabis useSubstance useLead variantsSchizophreniaGenetic variantsEuropean ancestryEuropean ancestry dataRisk-takingSCZHeritable factorsCannabisDisordersTobacco smokeGenetic correlationsGenome-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 surfaceGene × environment effects and mediation involving adverse childhood events, mood and anxiety disorders, and substance dependence
Kranzler H, Davis C, Feinn R, Jinwala Z, Khan Y, Oikonomou A, Silva-Lopez D, Burton I, Dixon M, Milone J, Ramirez S, Shifman N, Levey D, Gelernter J, Hartwell E, Kember R. Gene × environment effects and mediation involving adverse childhood events, mood and anxiety disorders, and substance dependence. Nature Human Behaviour 2024, 1-12. PMID: 38834750, DOI: 10.1038/s41562-024-01885-w.Peer-Reviewed Original ResearchAdverse childhood eventsSubstance dependenceMood/anxiety disordersAnxiety disordersChildhood eventsIndirect associationsGenetic riskExposure to adverse childhood eventsDevelopment of moodSubstance use disordersAssociations of adverse childhood eventsUse disorderMediation modelMood/anxietyDisorder factorsPolygenic scoresIndirect pathsDisordersEuropean ancestry individualsMoodTreatment approachesAnxietySelf-medicationEuropean ancestryLatent variablesDistinguishing vulnerability and resilience to posttraumatic stress disorder evaluating traumatic experiences, genetic risk and electronic health records
Løkhammer S, Koller D, Wendt F, Choi K, He J, Friligkou E, Overstreet C, Gelernter J, Hellard S, Polimanti R. Distinguishing vulnerability and resilience to posttraumatic stress disorder evaluating traumatic experiences, genetic risk and electronic health records. Psychiatry Research 2024, 337: 115950. PMID: 38744179, PMCID: PMC11156529, DOI: 10.1016/j.psychres.2024.115950.Peer-Reviewed Original ResearchElectronic health recordsPosttraumatic stress disorderHealth recordsPTSD vulnerabilityUK Biobank (UKBPhenome-wide association studyRisk scorePhenotype risk scoreUs Research ProgramPolygenic risk scoresStress disorderAoU participantsUKB participantsPresence of posttraumatic stress disorderTrauma burdenGenetic riskPosttraumatic stress disorder symptomsAssociation studiesPheWASClinical comorbiditiesComorbid associationsEye conditionsAOUInverse relationshipMultiple phenotypesAuthor Correction: A multi-ancestry genetic study of pain intensity in 598,339 veterans
Toikumo S, Vickers-Smith R, Jinwala Z, Xu H, Saini D, Hartwell E, Pavicic M, Sullivan K, Xu K, Jacobson D, Gelernter J, Rentsch C, Stahl E, Cheatle M, Zhou H, Waxman S, Justice A, Kember R, Kranzler H. Author Correction: A multi-ancestry genetic study of pain intensity in 598,339 veterans. Nature Medicine 2024, 1-1. PMID: 38714900, DOI: 10.1038/s41591-024-03024-4.Peer-Reviewed Original ResearchPolygenic liability for anxiety in association with comorbid anxiety in multiple sclerosis
Kowalec K, Harder A, Dolovich C, Fitzgerald K, Salter A, Lu Y, Bernstein C, Bolton J, Cutter G, Fisk J, Gelernter J, Graff L, Hägg S, Hitchon C, Levey D, Lublin F, McKay K, Patten S, Patki A, Stein M, Tiwari H, Wolinsky J, Marrie R. Polygenic liability for anxiety in association with comorbid anxiety in multiple sclerosis. Annals Of Clinical And Translational Neurology 2024, 11: 1393-1404. PMID: 38715244, PMCID: PMC11187942, DOI: 10.1002/acn3.52025.Peer-Reviewed Original ResearchPolygenic scoresEuropean genetic ancestryUK BiobankAnxious symptomsIncreased oddsGenetic ancestrySelf-reported physician-diagnosedGenetic burdenComorbid anxietyGenome-wide association studiesCase-control designUnited States cohortDirection of effectAssociated with comorbid anxietyPhysician-diagnosedAssociated with disability progressionIndex diseaseStates cohortAnxiety symptomsMeta-analysesAssociation studiesSummary statisticsCurrent symptomsPolygenic liabilityRisk predictionDissecting the Relationships Between Cannabis Use Disorder and Schizophrenia Using Genome-Wide Approaches
Johnson E, Levey D, Baranger D, Colbert S, Gelernter J, Agrawal A. Dissecting the Relationships Between Cannabis Use Disorder and Schizophrenia Using Genome-Wide Approaches. Biological Psychiatry 2024, 95: s28-s29. DOI: 10.1016/j.biopsych.2024.02.075.Peer-Reviewed Original ResearchGenetic influences and causal pathways shared between cannabis use disorder and other substance use traits
Galimberti M, Levey D, Deak J, Zhou H, Stein M, Gelernter J. Genetic influences and causal pathways shared between cannabis use disorder and other substance use traits. Molecular Psychiatry 2024, 1-6. PMID: 38580809, DOI: 10.1038/s41380-024-02548-y.Peer-Reviewed Original ResearchSubstance use disordersProblematic alcohol useSubstance use traitsCannabis use disorderCannabis useOpioid use disorderUse disorderGenomic structural equation modelingSmoking initiationLifetime cannabis useLegalization of cannabis useGlobal genetic correlationsProblematic substance useStructural equation modelingNicotine dependenceGenetic influencesCannabisSubstance useFagerstrom TestAlcohol useMendelian randomizationBidirectional relationshipGenetic correlationsDisordersSmoking cessation