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 phenotypesGenome-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 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 samples
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 MGEXPLORING 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 ancestryHuman genetics and epigenetics of alcohol use disorder
Zhou H, Gelernter J. Human genetics and epigenetics of alcohol use disorder. Journal Of Clinical Investigation 2024, 134: e172885. PMID: 39145449, PMCID: PMC11324314, DOI: 10.1172/jci172885.Peer-Reviewed Original ResearchConceptsEpigenome-wide association studiesEWAS studiesPower of GWASTranscriptome-wide associationGenome-wide scanAlcohol use disorderWhole-genome sequencingDrug-gene interactionsSingle-cell sequencingAssociation studiesDownstream analysisHuman geneticsGenetic variantsEpigenetic risk factorsVariant functionEpigenetic changesSpatial transcriptomicsUse disorderEpigeneticsDisease risk predictionGenetic correlationsDiversity of populationGeneticsComplex etiologyEnvironmental factorsGenome-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 surfaceDistinguishing 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 phenotypesPolygenic 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 predictionA phenome-wide association and Mendelian randomisation study of alcohol use variants in a diverse cohort comprising over 3 million individuals
Jennings M, Martínez-Magaña J, Courchesne-Krak N, Cupertino R, Vilar-Ribó L, Bianchi S, Hatoum A, Atkinson E, Giusti-Rodriguez P, Montalvo-Ortiz J, Gelernter J, Artigas M, 23andMe I, Aslibekyan S, Auton A, Babalola E, Bell R, Bielenberg J, Bryc K, Bullis E, Coker D, Partida G, Dhamija D, Das S, Elson S, Eriksson N, Filshtein T, Fitch A, Fletez-Brant K, Fontanillas P, Freyman W, Granka J, Heilbron K, Hernandez A, Hicks B, Hinds D, Jewett E, Jiang Y, Kukar K, Kwong A, Lin K, Llamas B, Lowe M, McCreight J, McIntyre M, Micheletti S, Moreno M, Nandakumar P, Nguyen D, Noblin E, O'Connell J, Petrakovitz A, Poznik G, Reynoso A, Schumacher M, Shastri A, Shelton J, Shi J, Shringarpure S, Su Q, Tat S, Tchakouté C, Tran V, Tung J, Wang X, Wang W, Weldon C, Wilton P, Wong C, Elson S, Edenberg H, Fontanillas P, Palmer A, Sanchez-Roige S. A phenome-wide association and Mendelian randomisation study of alcohol use variants in a diverse cohort comprising over 3 million individuals. EBioMedicine 2024, 103: 105086. PMID: 38580523, PMCID: PMC11121167, DOI: 10.1016/j.ebiom.2024.105086.Peer-Reviewed Original ResearchConceptsMultiple domains of healthDomains of healthEffects of alcohol consumptionAlcohol consumptionHealth outcomesPhenome-wide association studyAlcohol-related behaviorsCardio-metabolic healthPotential causal effectMendelian randomisation studiesGenome-wide association studiesPhenome-wide associationMR analysisPheWAS associationsMultiple domainsHypothesis-free approachPreventive medicineDiverse cohortPheWASAssociation studiesHealthReproductive healthAlcohol behaviorConsequences of drinkingEuropean cohortWhole-exome sequencing in UK Biobank reveals rare genetic architecture for depression
Tian R, Ge T, Kweon H, Rocha D, Lam M, Liu J, Singh K, Levey D, Gelernter J, Stein M, Tsai E, Huang H, Chabris C, Lencz T, Runz H, Chen C. Whole-exome sequencing in UK Biobank reveals rare genetic architecture for depression. Nature Communications 2024, 15: 1755. PMID: 38409228, PMCID: PMC10897433, DOI: 10.1038/s41467-024-45774-2.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesRare coding variantsWhole-exome sequencingGenetic architectureGenetic relationshipsLoss-of-function intolerant genesContribution of rare coding variantsRare damagingAssociated with risk of depressionElectronic health recordsUK Biobank participantsPolygenic risk scoresRisk of depressionAssociated with riskIntolerant genesRisk lociAssociation studiesCoding variantsBiobank participantsHealth recordsUK BiobankDepression definitionsDepression riskBurden analysisRare variantsGenetic and non-genetic predictors of risk for opioid dependence.
Na P, Deak J, Kranzler H, Pietrzak R, Gelernter J. Genetic and non-genetic predictors of risk for opioid dependence. Psychological Medicine 2024, 54: 1779-1786. PMID: 38317430, PMCID: PMC11132928, DOI: 10.1017/s0033291723003732.Peer-Reviewed Original ResearchPolygenic risk scoresMulti-trait analysis of genome-wide association studyOpioid use disorderPosttraumatic stress disorderPsychosocial/environmental factorsAnalysis of genome-wide association studiesHigher education levelGenome-wide association studiesNon-genetic predictorsEuropean-ancestry adultsEtiology of ODPublic health crisisPsychosocial factorsPolygenic riskMulti-trait analysisEducation levelPsychosocial environmentHousehold incomeRisk scoreAssociation studiesOpioid dependenceDiagnosis of ODLifetime diagnosisYale-PennAssociated with OD
2023
MULTI-ANCESTRY PHENOME-WIDE ASSOCIATION ANALYSES OF GENETIC LIABILITY FOR PROBLEMATIC ALCOHOL USE
Kember R, Johnson J, Johnston K, Lee H, Xu J, Davis L, Smoller J, Mallard T, Huckins L, Sanchez-Roige S, Kranzler H, Gelernter J, Zhou H. MULTI-ANCESTRY PHENOME-WIDE ASSOCIATION ANALYSES OF GENETIC LIABILITY FOR PROBLEMATIC ALCOHOL USE. European Neuropsychopharmacology 2023, 75: s10. DOI: 10.1016/j.euroneuro.2023.08.027.Peer-Reviewed Original ResearchDepression pathophysiology, risk prediction of recurrence and comorbid psychiatric disorders using genome-wide analyses
Als T, Kurki M, Grove J, Voloudakis G, Therrien K, Tasanko E, Nielsen T, Naamanka J, Veerapen K, Levey D, Bendl J, Bybjerg-Grauholm J, Zeng B, Demontis D, Rosengren A, Athanasiadis G, Bækved-Hansen M, Qvist P, Bragi Walters G, Thorgeirsson T, Stefánsson H, Musliner K, Rajagopal V, Farajzadeh L, Thirstrup J, Vilhjálmsson B, McGrath J, Mattheisen M, Meier S, Agerbo E, Stefánsson K, Nordentoft M, Werge T, Hougaard D, Mortensen P, Stein M, Gelernter J, Hovatta I, Roussos P, Daly M, Mors O, Palotie A, Børglum A. Depression pathophysiology, risk prediction of recurrence and comorbid psychiatric disorders using genome-wide analyses. Nature Medicine 2023, 29: 1832-1844. PMID: 37464041, PMCID: PMC10839245, DOI: 10.1038/s41591-023-02352-1.Peer-Reviewed Original ResearchConceptsSingle nucleotide polymorphism heritabilityGenome-wide analysisLikely causal genesFunctional genomics dataRisk variantsWide association studyPolygenic burdenPsychiatric disordersCausal genesPolygenic architectureGenomic dataRisk lociAssociation studiesSubgroups of depressionCause of disabilityDepression genetic riskCommon psychiatric disordersPrecision medicine approachCases of depressionOligodendrocyte lineageGenesLociConsiderable sex differencesGABAergic neuronsPsychiatric comorbidityIdentifying genetic loci and phenomic associations of substance use traits: A multi‐trait analysis of GWAS (MTAG) study
Xu H, Toikumo S, Crist R, Glogowska K, Jinwala Z, Deak J, Justice A, Gelernter J, Johnson E, Kranzler H, Kember R. Identifying genetic loci and phenomic associations of substance use traits: A multi‐trait analysis of GWAS (MTAG) study. Addiction 2023, 118: 1942-1952. PMID: 37156939, PMCID: PMC10754226, DOI: 10.1111/add.16229.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesSignificant single nucleotide polymorphismsSubstance use traitsMulti-trait analysisAssociation studiesGenetic architectureUse traitsGenome-wide significant single nucleotide polymorphismsProtein-protein interaction analysisTrait genetic architectureNumber of lociPolygenic risk scoresEuropean ancestry individualsNovel lociSingle nucleotide polymorphismsGenetic lociGWAS studiesLociMultiple related phenotypesNucleotide polymorphismsRelated phenotypesTraitsNovel associationsMTAgBiobank samplesMulti-trait genome-wide association analyses leveraging alcohol use disorder findings identify novel loci for smoking behaviors in the Million Veteran Program
Cheng Y, Dao C, Zhou H, Li B, Kember R, Toikumo S, Zhao H, Gelernter J, Kranzler H, Justice A, Xu K. Multi-trait genome-wide association analyses leveraging alcohol use disorder findings identify novel loci for smoking behaviors in the Million Veteran Program. Translational Psychiatry 2023, 13: 148. PMID: 37147289, PMCID: PMC10162964, DOI: 10.1038/s41398-023-02409-2.Peer-Reviewed Original ResearchConceptsSingle-trait genome-wide association studiesGenome-wide association studiesNovel lociPower of GWASJoint genome-wide association studyGenome-wide significant lociMillion Veteran ProgramGenome-wide associationSubstance use traitsGWAS summary statisticsNovel genetic variantsMulti-trait analysisFunctional annotationUse traitsSignificant lociHeritable traitMultiple lociAssociation studiesColocalization analysisLociPleiotropic effectsMTAgVeteran ProgramGenetic variantsTraits