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
Posttraumatic Stress Disorder, Obesity, and Accelerated Epigenetic Aging Among US Military Veterans
Fischer I, Na P, Nagamatsu S, Jeste D, Cabrera-Mendoza B, Montalvo-Ortiz J, Krystal J, Polimanti R, Gelernter J, Pietrzak R. Posttraumatic Stress Disorder, Obesity, and Accelerated Epigenetic Aging Among US Military Veterans. JAMA Psychiatry 2024, 81 PMID: 39476130, DOI: 10.1001/jamapsychiatry.2024.3403.Peer-Reviewed Original ResearchWhat Are the Genetic Building Blocks of Alcohol-Related Behaviors?
Gelernter J, Deak J. What Are the Genetic Building Blocks of Alcohol-Related Behaviors? American Journal Of Psychiatry 2024, 181: 952-954. PMID: 39482951, DOI: 10.1176/appi.ajp.20240885.Peer-Reviewed Original ResearchGenes in context: path to more precise risk prediction in psychiatry?
Na P, Pietrzak R, Gelernter J. Genes in context: path to more precise risk prediction in psychiatry? The British Journal Of Psychiatry 2024, 1-2. PMID: 39422146, DOI: 10.1192/bjp.2024.151.Peer-Reviewed Original ResearchConcerns about genetic risk testing for opioid use disorder
Hatoum A, Davis C, Kember R, Johnstone M, Oslin D, Zinkstok J, Burmeister M, Ethics P, Agrawal A, Kranzler H, Edenberg H, Gelernter J, Docherty A, Lencz T. Concerns about genetic risk testing for opioid use disorder. The Lancet Psychiatry 2024 PMID: 39413801, DOI: 10.1016/s2215-0366(24)00310-9.Peer-Reviewed Original ResearchT4. RELATIONSHIP OF GENETICALLY-INDEXED PHYSICAL ACTIVITY WITH MENTAL DISORDERS
Galimberti M, Gupta P, Deak J, Dao C, Nitin R, Zhou H, Harrington K, Na P, Topiwala A, Davis L, Gaziano M, Levey D, Stein M, Gelernter J. T4. RELATIONSHIP OF GENETICALLY-INDEXED PHYSICAL ACTIVITY WITH MENTAL DISORDERS. European Neuropsychopharmacology 2024, 87: 157-158. DOI: 10.1016/j.euroneuro.2024.08.314.Peer-Reviewed Original ResearchProtective effect of PAMental health traitsMillion Veteran ProgramEffects of PAGenome-wide association studiesPhysical activityLocal genetic correlationAlcohol consumptionPosttraumatic stress disorderSmoking initiationLeisure time PARelationship of PAUse disorderMental health outcomesPsychiatric disordersSelf-reported informationSubstance useAttention-deficit/hyperactivity disorderGenetic correlation analysisLocal genetic correlation analysisTime PAGenome-wide association study statisticsHealth traitsMR analysisResults PAF96. ALCOHOL USE AND DEMENTIA IN DIVERSE POPULATIONS
Topiwala A, Levey D, Zhou H, Deak J, Adhikari K, Ebmeier K, Bell S, Burgess S, Nichols T, Gaziano M, Stein M, Gelernter J. F96. ALCOHOL USE AND DEMENTIA IN DIVERSE POPULATIONS. European Neuropsychopharmacology 2024, 87: 256-257. DOI: 10.1016/j.euroneuro.2024.08.507.Peer-Reviewed Original ResearchMillion Veteran ProgramDementia riskMendelian randomizationDementia casesAlcohol usePrevalence of alcohol use disordersImpact of alcohol useRandom-effects meta-analysisAlcohol use disorder prevalenceProspective cohort studyStandard deviation increaseObservational associationsUK BiobankVeteran ProgramLevels of drinkingPopulation prevalenceAlcohol consumptionAlcohol use disorderCohort studyDisorder prevalenceDementiaDependent drinkersDose-response relationshipGenetic associationLight drinkersEXPLORING THE IMMUNOGENETIC BASIS OF POST-TRAUMATIC STRESS DISORDER
Braun A, Maihofer A, Katrinli S, Panagiotaropoulou G, Levey D, Ripke S, Gelernter J, Nievergelt C, Group P. EXPLORING THE IMMUNOGENETIC BASIS OF POST-TRAUMATIC STRESS DISORDER. European Neuropsychopharmacology 2024, 87: 4-5. DOI: 10.1016/j.euroneuro.2024.08.017.Peer-Reviewed Original ResearchGenome-wide association studiesAssociation analysisPost-traumatic stress disorderMajor histocompatibility complexHuman leukocyte antigen imputationComplex linkage disequilibrium structureGenomes reference panelLinkage disequilibrium structureMajor histocompatibility complex class III regionRisk-conferring allelesClass III regionPsychiatric Genomics ConsortiumHuman leukocyte antigen allelesMillion Veteran ProgramDisequilibrium structureLatin American ancestryRisk lociRisk-conferring variantsCross-ancestryAssociation studiesPopulation stratificationReference panelGenetic variantsSusceptibility to post-traumatic stress disorderAmerican ancestryPOST-GWAS FOR PTSD: FROM RISK LOCI TO BIOLOGICAL MEANING
Nievergelt C, Ongeri L, Gelernter J. POST-GWAS FOR PTSD: FROM RISK LOCI TO BIOLOGICAL MEANING. European Neuropsychopharmacology 2024, 87: 2-3. DOI: 10.1016/j.euroneuro.2024.08.013.Peer-Reviewed Original ResearchPosttraumatic stress disorderPGC-PTSDLocal ancestry inferencePTSD associationsRisk lociPosttraumatic stress disorder casenessThreat-related processingGenome-wide association study resultsCo-morbid disordersComplex patterns of admixtureStress-related disordersMental health disordersPatterns of admixturePotential causal genesMajor histocompatibility complexMental health consequencesAssociation study resultsMDD patientsMulti-omics approachStress disorderMulti-omics studiesHuman leukocyte antigenAncestry inferenceAdmixed individualsMDD