2024
Genetic 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 ODGenetic contribution to the comorbidity between attention-deficit/hyperactivity disorder and substance use disorders
Koller D, Mitjans M, Kouakou M, Friligkou E, Cabrera-Mendoza B, Deak J, Llonga N, Pathak G, Stiltner B, Løkhammer S, Levey D, Zhou H, Hatoum A, Kember R, Kranzler H, Stein M, Corominas R, Demontis D, Artigas M, Ramos-Quiroga J, Gelernter J, Ribasés M, Cormand B, Polimanti R. Genetic contribution to the comorbidity between attention-deficit/hyperactivity disorder and substance use disorders. Psychiatry Research 2024, 333: 115758. PMID: 38335780, PMCID: PMC11157987, DOI: 10.1016/j.psychres.2024.115758.Peer-Reviewed Original ResearchConceptsUse disorderGenome-wide association studiesGenomic structural equation modelingCannabis use disorderAlcohol Use Disorders Identification TestAttention-deficit/hyperactivity disorderAlcohol use disorderProblematic alcohol useSubstance use disordersTwo-sample Mendelian randomization analysisLinkage disequilibrium score regression analysisDisorders Identification TestMendelian randomization analysisAssociated with increased oddsOdds of ADHDOpioid use disorderAttention-deficit/hyperactivityGWAS meta-analysesAlcohol dependenceStructural equation modelingNicotine dependenceInvestigate genetic correlationsADHDPolygenic riskStrength of evidence
2022
Unique 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 interest
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 geneStyleVeteransPolygenic 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 soldiersPolygenic risk for traumatic loss-related PTSD in US military veterans: Protective effect of secure attachment style
Asch RH, Esterlis I, Wendt FR, Kachadourian L, Southwick SM, Gelernter J, Polimanti R, Pietrzak RH. Polygenic risk for traumatic loss-related PTSD in US military veterans: Protective effect of secure attachment style. The World Journal Of Biological Psychiatry 2021, 22: 792-799. PMID: 33821766, PMCID: PMC8925016, DOI: 10.1080/15622975.2021.1907721.Peer-Reviewed Original ResearchConceptsAttachment styleSecure attachment styleRe-experiencing symptomsPolygenic riskAttachment securityPsychological treatmentTraumatic eventsPositive screenPTSDStyle interactionPolygenic risk scoresUS military veteransMilitary veteransNeuroplasticity processesGenetic liabilityStyleSignificant predictorsVeteransUS veteransAssociationPredictorsScreenScoresSeverityRelationshipDissecting 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
2018
Genome-wide analysis of insomnia disorder
Stein MB, McCarthy MJ, Chen CY, Jain S, Gelernter J, He F, Heeringa SG, Kessler RC, Nock MK, Ripke S, Sun X, Wynn GH, Smoller JW, Ursano RJ. Genome-wide analysis of insomnia disorder. Molecular Psychiatry 2018, 23: 2238-2250. PMID: 29520036, PMCID: PMC6129221, DOI: 10.1038/s41380-018-0033-5.Peer-Reviewed Original ResearchMeSH KeywordsAdultBlack or African AmericanCohort StudiesDepressive Disorder, MajorDiabetes Mellitus, Type 2FemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHispanic or LatinoHumansMaleMilitary PersonnelMultifactorial InheritancePolymorphism, Single NucleotideRisk FactorsSleep Initiation and Maintenance DisordersWhite PeopleYoung AdultConceptsGenome-wide association studiesAncestral groupsGenome-wide significant lociGenome-wide analysisGene-based associationSignificant gene-based associationsSleep-related traitsGenetic risk variantsSignificant lociChr 7Heritable basisChr 9Association studiesRisk variantsGenetic contributionLociUK BiobankMetabolic diseasesRFX3Genetic riskTraitsHeritabilityPolygenic riskTwin studiesDeleterious health effects
2017
Polygenic 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