2024
Distinguishing 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 phenotypesGenetic 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 samplePredispositionDoes 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 studies
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 levelsVeteransSuicidalityPOLYGENIC RISK SCORE FOR THE PREDICTION OF ALCOHOL USE DISORDER COMORBIDITIES IN THE NATIONAL HEALTH AND RESILIENCE IN VETERANS STUDY COHORT
Mendoza B, De Lillo A, Gelernter J, Pietrzak R, Polimanti R. POLYGENIC RISK SCORE FOR THE PREDICTION OF ALCOHOL USE DISORDER COMORBIDITIES IN THE NATIONAL HEALTH AND RESILIENCE IN VETERANS STUDY COHORT. European Neuropsychopharmacology 2022, 63: e161-e162. DOI: 10.1016/j.euroneuro.2022.07.295.Peer-Reviewed Original ResearchPhenome-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
Psychosocial 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 studiesPolygenic risk for major depression is associated with lifetime suicide attempt in US soldiers independent of personal and parental history of major depression
Stein MB, Jain S, Campbell‐Sills L, Ware EB, Choi KW, He F, Ge T, Gelernter J, Smoller JW, Kessler RC, Ursano RJ. Polygenic risk for major depression is associated with lifetime suicide attempt in US soldiers independent of personal and parental history of major depression. American Journal Of Medical Genetics Part B Neuropsychiatric Genetics 2021, 186: 469-475. PMID: 34288400, PMCID: PMC8692314, DOI: 10.1002/ajmg.b.32868.Peer-Reviewed Original ResearchConceptsMajor depressive disorderLifetime suicide attemptsParental historySuicide attemptsMajor depressionMDD-PRSMultivariable modelLifetime historyMajor public health problemIncident suicide attemptsPolygenic riskPublic health problemUS Army soldiersRisk stratificationDepressive disorderPolygenic risk scoresRisk scoreSecond cohortHealth problemsCommon genetic variantsFirst cohortPersonal historyCohortGenetic variantsArmy soldiersPsychological trauma and the genetic overlap between posttraumatic stress disorder and major depressive disorder
Mundy J, Hübel C, Gelernter J, Levey D, Murray RM, Skelton M, Stein MB, Maihofer A, Nievergelt C, Baker D, Risborough V, Calabrese J, Galea S, Stein D, Koen N, Dalvie S, Aiello A, Roberts A, Koenen K, Solovieff N, Kranzler H, Zhao H, Gelernter J, Farrer L, Johnson E, Rice J, Bierut L, Saccone N, McFarlane A, Forbes D, Silove D, O'Donnell M, Bryant R, van Hooff M, Sponheim S, Disner S, Pietrzak R, Chen C, Smoller J, Stein M, Ursano R, Kessler R, Junglen A, Delahanty D, Amstadter A, Sheerin C, Ruggiero K, McLaughlin K, Peverill M, Caldas-de-Almeida J, Austin S, Gelaye B, Williams M, Sanchez S, Franz C, Panizzon M, Lyons M, Kremen W, Andreassen O, Dale A, Rutten B, Vinkers C, Schijven D, Geuze E, Vermetten E, Luykx J, Boks M, Ashley-Koch A, Beckham J, Garrett M, Hauser M, Dennis M, Kimbrel N, Qin X, Karstoft K, Andersen S, Borglum A, Hougaard D, Bybjerg-Grauholm J, Duncan L, Bµkvad-Hansen M, Nordentoft M, Mors O, Mortensen P, Werge T, Thompson W, Wang Y, Heath A, Nelson E, Martin N, Gordon S, Wolf E, Logue M, Miller M, McGlinchey R, Milberg W, Erbes C, Polusny M, Arbisi P, Peterson A, Williamson D, Young K, Maurer D, Rothbaum A, Zoellner L, Mavissakalian M, Feeny N, Roy-Byrne P, Rothbaum B, Maples-Keller J, Khan A, Wolff J, Lebois L, Teicher M, Kaufman M, Winternitz S, Bolger E, Seligowski A, Orcutt H, Evans A, Lugonja B, Lewis C, Jones I, Bisson J, McLean S, Linnstaedt S, Peters E, Rung A, Trapido E, Brashear M, Lori A, Smith A, Bradley B, Gillespie C, Guffanti G, Ressler K, Almli L, Jovanovic T, Bustamante A, Uddin M, van den Heuvel L, Seedat S, Hemmings S, Uka A, Kulenovic A, Wolf C, Babic D, Avdibegovic E, Deckert J, Domschke K, Jakovljevic M, Marmar C, Flory J, Jett M, Yehuda R, Hammamieh R, King A, Liberzon I, Seng J, Morris C, Mehta D, Voisey J, Lawford B, Young R, McLeay S, Daskalakis N, Norman S, Wang Z, Breen G, Coleman J, Klengel T, Torres K, Choi K, Levey D, Polimanti R, Atkinson E, Martin A, Neale B, Daly M, Ripke S, Ratanatharathorn A, Provost A, Haas M, Stevens J, Morey R, Harnal S, Mortensen P, Seedat S, Sumner J, Vassos E, Breen G, Coleman J. Psychological trauma and the genetic overlap between posttraumatic stress disorder and major depressive disorder. Psychological Medicine 2021, 52: 3975-3984. PMID: 34085609, PMCID: PMC8962503, DOI: 10.1017/s0033291721000830.Peer-Reviewed Original ResearchRecurrent major depressive disorderMajor depressive disorderPosttraumatic stress disorderSingle-episode major depressive disorderDepressive disorderTrauma exposureStress disorderPsychological trauma exposureLifetime major depressive disorderTrauma sensitivityGenetic loadingUK Biobank participantsKey risk factorsMental health consequencesRisk factorsMillion Veteran ProgramPolygenic risk scoresRisk scoreGenetic overlapHealth consequencesBiobank participantsTraumaDisordersVeteran ProgramPsychiatric Genomics ConsortiumDissecting the heterogeneity of posttraumatic stress disorder: differences in polygenic risk, stress exposures, and course of PTSD subtypes
Campbell-Sills L, Sun X, Choi KW, He F, Ursano RJ, Kessler RC, Levey DF, Smoller JW, Gelernter J, Jain S, Stein MB. Dissecting the heterogeneity of posttraumatic stress disorder: differences in polygenic risk, stress exposures, and course of PTSD subtypes. Psychological Medicine 2021, 52: 3646-3654. PMID: 33947479, PMCID: PMC9772910, DOI: 10.1017/s0033291721000428.Peer-Reviewed Original ResearchPosttraumatic stress disorderPersistence of PTSDMajor depressionPTSD subtypesStress disorderCo-occurring major depressionStress exposureMonths postdeploymentCourse of PTSDPolygenic riskProbable posttraumatic stress disorderU.S. Army Brigade Combat TeamHigh polygenic riskConcurrent mental disordersGenetic risk factorsTrauma-related factorsHigh symptom profileLeast comorbidityProspective studyRisk factorsDepressive disorderTreatment responsePolygenic risk scoresRisk scoreComorbidities
2020
Leveraging genome-wide data to investigate differences between opioid use vs. opioid dependence in 41,176 individuals from the Psychiatric Genomics Consortium
Polimanti R, Walters RK, Johnson EC, McClintick JN, Adkins AE, Adkins DE, Bacanu SA, Bierut LJ, Bigdeli TB, Brown S, Bucholz KK, Copeland WE, Costello EJ, Degenhardt L, Farrer LA, Foroud TM, Fox L, Goate AM, Grucza R, Hack LM, Hancock DB, Hartz SM, Heath AC, Hewitt JK, Hopfer CJ, Johnson EO, Kendler KS, Kranzler HR, Krauter K, Lai D, Madden PAF, Martin NG, Maes HH, Nelson EC, Peterson RE, Porjesz B, Riley BP, Saccone N, Stallings M, Wall TL, Webb BT, Wetherill L, Edenberg H, Agrawal A, Gelernter J. Leveraging genome-wide data to investigate differences between opioid use vs. opioid dependence in 41,176 individuals from the Psychiatric Genomics Consortium. Molecular Psychiatry 2020, 25: 1673-1687. PMID: 32099098, PMCID: PMC7392789, DOI: 10.1038/s41380-020-0677-9.Peer-Reviewed Original Research
2017
Trauma exposure interacts with the genetic risk of bipolar disorder in alcohol misuse of US soldiers
Polimanti R, Kaufman J, Zhao H, Kranzler HR, Ursano RJ, Kessler RC, Stein MB, Gelernter J. Trauma exposure interacts with the genetic risk of bipolar disorder in alcohol misuse of US soldiers. Acta Psychiatrica Scandinavica 2017, 137: 148-156. PMID: 29230810, PMCID: PMC6110087, DOI: 10.1111/acps.12843.Peer-Reviewed Original ResearchConceptsBD polygenic risk scorePolygenic risk scoresAlcohol misuseBipolar disorderTrauma exposurePsychiatric disordersGenetic riskMajor depressive disorderNicotine dependence symptomsSubstance use disordersSchizophrenia polygenic risk scoresVoltage-gated calcium channel activityCalcium channel activityUS Army soldiersBeta2-adrenergic receptorDepressive disorderRisk scoreUse disordersAdrenergic receptorsMental disordersSubstance abuseDisordersDependence symptomsChannel activityExposurePolygenic Scores for Major Depressive Disorder and Risk of Alcohol Dependence
Andersen AM, Pietrzak RH, Kranzler HR, Ma L, Zhou H, Liu X, Kramer J, Kuperman S, Edenberg HJ, Nurnberger JI, Rice JP, Tischfield JA, Goate A, Foroud TM, Meyers JL, Porjesz B, Dick DM, Hesselbrock V, Boerwinkle E, Southwick SM, Krystal JH, Weissman MM, Levinson DF, Potash JB, Gelernter J, Han S. Polygenic Scores for Major Depressive Disorder and Risk of Alcohol Dependence. JAMA Psychiatry 2017, 74: 1153-1160. PMID: 28813562, PMCID: PMC5710224, DOI: 10.1001/jamapsychiatry.2017.2269.Peer-Reviewed Original ResearchConceptsMDD polygenic risk scoresMajor depressive disorderPolygenic risk scoresAlcohol dependenceDepressive disorderSignificant public health burdenPublic health burdenAD comorbidityNational HealthHealth burdenMAIN OUTCOMECase-control statusRisk scoreRisk of ADVeterans StudyYale-PennGenetic susceptibilityMDD statusCommon genetic factorsSubstance dependenceMDD casesAD samplesPolygenic riskGenetic factorsHeritable disorder