Featured Publications
Genome-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 MGDistinguishing 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 phenotypesWhole-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 ODPolygenic risk for suicide attempt is associated with lifetime suicide attempt in US soldiers independent of parental risk
Stein M, Jain S, Papini S, Campbell-Sills L, Choi K, Martis B, Sun X, He F, Ware E, Naifeh J, Aliaga P, Ge T, Consortium F, Workgroup F, Program F, Consortium F, Smoller J, Gelernter J, Kessler R, Ursano R. Polygenic risk for suicide attempt is associated with lifetime suicide attempt in US soldiers independent of parental risk. Journal Of Affective Disorders 2024, 351: 671-682. PMID: 38309480, PMCID: PMC11259154, DOI: 10.1016/j.jad.2024.01.254.Peer-Reviewed Original ResearchConceptsHistory of Major Depressive DisorderMajor depressive disorderNon-suicidal self-injuryLifetime non-suicidal self-injuryHistory of SAAssociated with lifetime SAParental historyMultivariate modelLifetime SASuicide attemptsParental major depressive disorderAssociated with non-suicidal self-injuryAssociated with lifetime suicide attemptsLifetime suicide attemptsClinical decision-makingDepressive disorderGWA studiesPolygenic risk scoresRisk scoreCohortEuropean ancestrySelf-injuryParental SAGenetic liabilityCombined analysisCorrection: Psychosocial moderators of polygenic risk scores of inflammatory biomarkers in relation to GrimAge
Tamman A, Koller D, Nagamatsu S, Cabrera-Mendoza B, Abdallah C, Krystal J, Gelernter J, Montalvo-Ortiz J, Polimanti R, Pietrzak R. Correction: Psychosocial moderators of polygenic risk scores of inflammatory biomarkers in relation to GrimAge. Neuropsychopharmacology 2024, 49: 764-764. PMID: 38182778, PMCID: PMC10876612, DOI: 10.1038/s41386-023-01786-y.Peer-Reviewed Original Research
2023
Psychosocial moderators of polygenic risk scores of inflammatory biomarkers in relation to GrimAge
Tamman A, Koller D, Nagamatsu S, Cabrera-Mendoza B, Abdallah C, Krystal J, Gelernter J, Montalvo-Ortiz J, Polimanti R, Pietrzak R. Psychosocial moderators of polygenic risk scores of inflammatory biomarkers in relation to GrimAge. Neuropsychopharmacology 2023, 49: 699-708. PMID: 37848731, PMCID: PMC10876568, DOI: 10.1038/s41386-023-01747-5.Peer-Reviewed Original ResearchPolygenic risk scoresRisk scoreGenetic predispositionModifiable psychosocial variablesAge-related morbidityGamma-glutamyl transferaseInflammatory biomarkersSystemic inflammationNational HealthApolipoprotein BMale veteransPsychosocial factorsVeterans StudySaliva samplesPsychosocial moderatorsPsychosocial variablesAntihistamine drugsMilitary veteransGrimAgeGrimAge accelerationInflammationUK BiobankDrugsRepresentative samplePredispositionMULTI-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 ResearchPositive personality traits moderate persistent high alcohol consumption, determined by polygenic risk in U.S. military veterans: results from a 10-year, population-based, observational cohort study
Na P, Zhou H, Montalvo-Ortiz J, Cabrera-Mendoza B, Petrakis I, Krystal J, Polimanti R, Gelernter J, Pietrzak R. Positive personality traits moderate persistent high alcohol consumption, determined by polygenic risk in U.S. military veterans: results from a 10-year, population-based, observational cohort study. Psychological Medicine 2023, 53: 7893-7901. PMID: 37642191, DOI: 10.1017/s003329172300199x.Peer-Reviewed Original ResearchIdentifying 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 samplesDoes polygenic risk for substance‐related traits predict ages of onset and progression of symptoms?
Kranzler H, Feinn R, Xu H, Ho B, Saini D, Nicastro O, Jacoby A, Toikumo S, Gelernter J, Hartwell E, Kember R. Does polygenic risk for substance‐related traits predict ages of onset and progression of symptoms? Addiction 2023, 118: 1675-1686. PMID: 37069489, PMCID: PMC10525011, DOI: 10.1111/add.16210.Peer-Reviewed Original ResearchConceptsOpioid use disorderSubstance use disordersProgression of symptomsPolygenic risk scoresAlcohol use disorderUse disordersAfrican ancestry individualsGenetic riskRegular useEuropean ancestry individualsEarly onsetMore rapid progressionRegular alcohol useShorter progression timeAge of onsetFirst substance useDiscovery sampleUS inpatientsOnset of problemsOutpatient settingDisease progressionRapid progressionSymptom progressionRisk scoreGenome-wide association studiesMultivariate genome-wide association meta-analysis of over 1 million subjects identifies loci underlying multiple substance use disorders
Hatoum A, Colbert S, Johnson E, Huggett S, Deak J, Pathak G, Jennings M, Paul S, Karcher N, Hansen I, Baranger D, Edwards A, Grotzinger A, Tucker-Drob E, Kranzler H, Davis L, Sanchez-Roige S, Polimanti R, Gelernter J, Edenberg H, Bogdan R, Agrawal A. Multivariate genome-wide association meta-analysis of over 1 million subjects identifies loci underlying multiple substance use disorders. Nature Mental Health 2023, 1: 210-223. PMID: 37250466, PMCID: PMC10217792, DOI: 10.1038/s44220-023-00034-y.Peer-Reviewed Original ResearchGenome-wide associationGenetic risk lociIndependent single nucleotide polymorphismsProblematic tobacco useSingle nucleotide polymorphismsRisk lociHigh polygenicityLociReceptor geneAddiction risk factorsPolygenic risk scoresEuropean descentPolygenicityGenesSummary statisticsSubstance use disordersSomatic conditionsAncestryRegulationConfersUse disordersPolymorphismGenetic liabilityDopamine regulationPDE4B
2022
Genetic liability to suicidal thoughts and behaviors and risk of suicide attempt in US military veterans: moderating effects of cumulative trauma burden
Nichter B, Koller D, De Angelis F, Wang J, Girgenti M, Na P, Hill M, Norman S, Krystal J, Gelernter J, Polimanti R, Pietrzak R. Genetic liability to suicidal thoughts and behaviors and risk of suicide attempt in US military veterans: moderating effects of cumulative trauma burden. Psychological Medicine 2022, 53: 6325-6333. PMID: 36444557, DOI: 10.1017/s0033291722003646.Peer-Reviewed Original ResearchConceptsPolygenic risk scoresUS military veteransLifetime suicide attemptsSuicide attemptsTrauma exposureTrauma burdenGenetic liabilityMilitary veteransDrug repurposing analysisPopulation-based sampleCumulative trauma exposureLifetime trauma exposureLow trauma exposureSuicide prediction modelsChronic inflammationInflammatory processNervous system developmentRisk scorePsychiatric characteristicsSuicidal behaviorExposure interactionsLarge genome-wide association studiesHigh levelsVeteransSuicidalityPhenome-wide Association Analysis of Substance Use Disorders in a Deeply Phenotyped Sample
Kember RL, Hartwell EE, Xu H, Rotenberg J, Almasy L, Zhou H, Gelernter J, Kranzler HR. Phenome-wide Association Analysis of Substance Use Disorders in a Deeply Phenotyped Sample. Biological Psychiatry 2022, 93: 536-545. PMID: 36273948, PMCID: PMC9931661, DOI: 10.1016/j.biopsych.2022.08.010.Peer-Reviewed Original ResearchConceptsSubstance use disordersAlcohol use disorderOpioid use disorderPolygenic risk scoresUse disordersCo-occurring psychiatric disordersComprehensive psychiatric interviewSemi-Structured AssessmentElectronic health recordsControl subjectsLow prevalencePsychiatric interviewRisk scorePsychiatric disordersPhenome-wide association analysisDrug dependenceEuropean individualsHealth recordsLifetime cannabisPhenome-wide association studyDisordersAfrican ancestry individualsDSM diagnosesPopulation sampleGenetic liabilityUnique and joint associations of polygenic risk for major depression and opioid use disorder with endogenous opioid system function
Love T, Shabalin AA, Kember RL, Docherty AR, Zhou H, Koppelmans V, Gelernter J, Baker AK, Hartwell E, Dubroff J, Zubieta JK, Kranzler HR. Unique and joint associations of polygenic risk for major depression and opioid use disorder with endogenous opioid system function. Neuropsychopharmacology 2022, 47: 1784-1790. PMID: 35545664, PMCID: PMC9372136, DOI: 10.1038/s41386-022-01325-1.Peer-Reviewed Original ResearchConceptsOpioid use disorderMajor depressive disorderPolygenic risk scoresUse disordersEndogenous opioid system functionOpioid system functionOpioid system activityMDD polygenic risk scoresPolygenic riskAssociation of PRSEndogenous opioid responseOpioid system activationNon-displaceable bindingPathophysiologic linkOpioid responseMOR availabilityOpioid releaseDepressive disorderMajor depressionNeurotransmitter systemsVentral pallidumRisk scoreReceptor concentrationSystem activationRegion of interestGenome-wide meta-analysis of alcohol use disorder in East Asians
Zhou H, Kalayasiri R, Sun Y, Nuñez YZ, Deng HW, Chen XD, Justice AC, Kranzler HR, Chang S, Lu L, Shi J, Sanichwankul K, Mutirangura A, Malison RT, Gelernter J. Genome-wide meta-analysis of alcohol use disorder in East Asians. Neuropsychopharmacology 2022, 47: 1791-1797. PMID: 35094024, PMCID: PMC9372033, DOI: 10.1038/s41386-022-01265-w.Peer-Reviewed Original ResearchConceptsAlcohol use disorderAlcohol dependenceUse disordersICD-9-CM diagnosisGenome-wide association studiesEast Asian subjectsElectronic health recordsPack yearsLeading causePolygenic risk scoresThai cohortRisk scoreAlcohol consumptionDSM-IVAsian subjectsCohortMillion Veteran Program sampleHealth recordsLarge genome-wide association studiesEast AsiansOngoing recruitmentRisk genesDisordersRisk lociSubjects
2021
Drinking and smoking polygenic risk is associated with childhood and early-adulthood psychiatric and behavioral traits independently of substance use and psychiatric genetic risk
De Angelis F, Wendt FR, Pathak GA, Tylee DS, Goswami A, Gelernter J, Polimanti R. Drinking and smoking polygenic risk is associated with childhood and early-adulthood psychiatric and behavioral traits independently of substance use and psychiatric genetic risk. Translational Psychiatry 2021, 11: 586. PMID: 34775470, PMCID: PMC8590689, DOI: 10.1038/s41398-021-01713-z.Peer-Reviewed Original ResearchConceptsSubstance useYoung adultsBehavioral traitsPhiladelphia Neurodevelopmental CohortRemoval of participantsAnxiety-related traitsRisk-taking behaviorVerbal reasoningCognitive performancePolygenic risk scoresSocial competenciesNeurobiological processesNeurodevelopmental CohortPsychiatric genetic riskDrinking behaviorParent educationPRS associationsPolygenic riskPsychopathologyGenetic overlapPsychotic symptomsAdverse health outcomesHazardous behaviorEducational attainmentTobacco smokingPsychosocial moderators of polygenic risk for suicidal ideation: Results from a 7-year population-based, prospective cohort study of U.S. veterans
Na PJ, De Angelis F, Nichter B, Wendt FR, Krystal JH, Southwick SM, Levey DF, Gelernter J, Polimanti R, Pietrzak RH. Psychosocial moderators of polygenic risk for suicidal ideation: Results from a 7-year population-based, prospective cohort study of U.S. veterans. Molecular Psychiatry 2021, 27: 1068-1074. PMID: 34725455, DOI: 10.1038/s41380-021-01352-2.Peer-Reviewed Original ResearchConceptsNew-onset suicidal ideationChronic suicidal ideationPolygenic risk scoresSuicidal ideationProspective cohort studyPolygenic riskRisk of SIHigher baseline levelsHigh polygenic riskModifiable psychosocial factorsSocial supportDispositional optimismCohort studyProspective cohortUS veteransSymptomatic courseRisk scorePsychosocial factorsGenome-wide association studiesBaseline levelsU.S. veteransSuicidal thoughtsPsychosocial moderatorsStudy periodLarge genome-wide association studiesAttachment Style Moderates Polygenic Risk for Incident Posttraumatic Stress in U.S. Military Veterans: A 7-Year, Nationally Representative, Prospective Cohort Study
Tamman AJF, Wendt FR, Pathak GA, Krystal JH, Southwick SM, Sippel LM, Gelernter J, Polimanti R, Pietrzak RH. Attachment Style Moderates Polygenic Risk for Incident Posttraumatic Stress in U.S. Military Veterans: A 7-Year, Nationally Representative, Prospective Cohort Study. Biological Psychiatry 2021, 91: 637-646. PMID: 34955171, DOI: 10.1016/j.biopsych.2021.09.025.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderAttachment styleU.S. military veteransIncident posttraumatic stress disorderSocial environmental factorsDevelopment of PTSDMilitary veteransInsecure attachment stylesSecure attachment stylePolygenic riskEffect of PRSLifetime trauma burdenPTSD preventionPosttraumatic stressPTSD developmentPTSD symptomsStress disorderPolygenic risk scoresHigh polygenic riskProspective designNationally RepresentativePotential pharmacotherapyMultivariate geneStyleVeterans