2022
An Atlas of Genetic Correlations and Genetically Informed Associations Linking Psychiatric and Immune-Related Phenotypes
Tylee DS, Lee YK, Wendt FR, Pathak GA, Levey DF, De Angelis F, Gelernter J, Polimanti R. An Atlas of Genetic Correlations and Genetically Informed Associations Linking Psychiatric and Immune-Related Phenotypes. JAMA Psychiatry 2022, 79: 667-676. PMID: 35507366, PMCID: PMC9069342, DOI: 10.1001/jamapsychiatry.2022.0914.Peer-Reviewed Original ResearchConceptsRisk factorsImmune-related phenotypesMultivariable adjustmentUlcerative colitisCrohn's diseaseMendelian randomizationImmune-related disordersReciprocal risk factorsHealth-related behaviorsPsychiatric phenotypesFalse discovery rate correctionAllergic rhinitisGenetic association studiesGenetic associationInflammatory disordersClinical associationsMajor depressionImmune disordersMAIN OUTCOMEPsychiatric disordersSocial determinantsDisordersAssociation studiesColitisAsthmaUnique 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
Polygenic 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 soldiersDissecting 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
Multivariate genome-wide analysis of education, socioeconomic status and brain phenome
Wendt FR, Pathak GA, Lencz T, Krystal JH, Gelernter J, Polimanti R. Multivariate genome-wide analysis of education, socioeconomic status and brain phenome. Nature Human Behaviour 2020, 5: 482-496. PMID: 33349686, PMCID: PMC8068566, DOI: 10.1038/s41562-020-00980-y.Peer-Reviewed Original ResearchConceptsPsychosocial factorsSocioeconomic statusPsychiatric disordersBipolar disorderGenetic riskNeuronal cell typesMajor depressionTourette syndromeBrain morphologyDisordersImaging phenotypesCell typesRisky behaviorsPsychopathologyGenetic overlapRiskGenetic discoveriesPsychiatric traitsStatusSyndrome
2019
Evidence of causal effect of major depression on alcohol dependence: findings from the psychiatric genomics consortium
Polimanti R, Peterson RE, Ong JS, MacGregor S, Edwards AC, Clarke TK, Frank J, Gerring Z, Gillespie NA, Lind PA, Maes HH, Martin NG, Mbarek H, Medland SE, Streit F, Agrawal A, Edenberg H, Kendler K, Lewis C, Sullivan P, Wray N, Gelernter J, Derks E. Evidence of causal effect of major depression on alcohol dependence: findings from the psychiatric genomics consortium. Psychological Medicine 2019, 49: 1218-1226. PMID: 30929657, PMCID: PMC6565601, DOI: 10.1017/s0033291719000667.Peer-Reviewed Original ResearchConceptsMajor depressionAlcohol dependenceAlcohol consumptionPsychiatric Genomics ConsortiumImportant public health concernMendelian randomizationPublic health concernUK BiobankClinical associationsHealth concernMR analysisReverse causationCausal roleNon-significant resultsCausal relationshipGenetic liabilityGenomics ConsortiumLinkage disequilibrium score regressionIntervention efforts
2016
Genome-wide Association Study of Cannabis Dependence Severity, Novel Risk Variants, and Shared Genetic Risks
Sherva R, Wang Q, Kranzler H, Zhao H, Koesterer R, Herman A, Farrer LA, Gelernter J. Genome-wide Association Study of Cannabis Dependence Severity, Novel Risk Variants, and Shared Genetic Risks. JAMA Psychiatry 2016, 73: 472. PMID: 27028160, PMCID: PMC4974817, DOI: 10.1001/jamapsychiatry.2016.0036.Peer-Reviewed Original ResearchConceptsCannabis dependenceNeuronal calcium homeostasisGenetic factorsMajor depressive disorderSushi multiple domains-1 (CSMD1) geneSubstance abuse treatment centersSpecific genetic risk factorsGenetic risk factorsShared genetic riskPotential genetic factorsCentral nervous system developmentCriterion countsCannabis dependence severityDomain 1 geneCAD riskMean ageRisk factorsDepressive disorderNervous system developmentMajor depressionLarge cohortMAIN OUTCOMEGenome-wide association studiesTreatment centersCalcium homeostasis
2010
Early-life stress, corticotropin-releasing factor, and serotonin transporter gene: A pilot study
Coplan JD, Abdallah CG, Kaufman J, Gelernter J, Smith EL, Perera TD, Dwork AJ, Kaffman A, Gorman JM, Rosenblum LA, Owens MJ, Nemeroff CB. Early-life stress, corticotropin-releasing factor, and serotonin transporter gene: A pilot study. Psychoneuroendocrinology 2010, 36: 289-293. PMID: 20692103, PMCID: PMC3017732, DOI: 10.1016/j.psyneuen.2010.07.011.Peer-Reviewed Original ResearchConceptsEarly life stressCSF CRF concentrationsCRF concentrationsCerebrospinal fluid corticotropin-releasing factor concentrationsCorticotropin-releasing factor concentrationsPilot studyNonhuman primate modelCorticotropin-releasing factorYears of ageEarly life adversitySerotonin transporter gene polymorphismPersistent elevationTransporter gene polymorphismPrimate modelMajor depressionCSF samplesDepressive symptomsGene polymorphismsAllele groupFactor concentrationsLFD conditionsMale bonnet macaquesChildhood abuseSubsequent developmentBonnet macaques
2009
Subtypes of major depression in substance dependence
Niciu MJ, Chan G, Gelernter J, Arias AJ, Douglas K, Weiss R, Anton RF, Farrer L, Cubells JF, Kranzler HR. Subtypes of major depression in substance dependence. Addiction 2009, 104: 1700-1709. PMID: 19681804, PMCID: PMC2980795, DOI: 10.1111/j.1360-0443.2009.02672.x.Peer-Reviewed Original ResearchMeSH KeywordsAcademic Medical CentersAdolescentAdultAge FactorsAnxiety DisordersBlack or African AmericanComorbidityData Interpretation, StatisticalDepressive Disorder, MajorFemaleHispanic or LatinoHumansInterview, PsychologicalLogistic ModelsMaleRecurrenceSocioeconomic FactorsSubstance-Related DisordersSuicide, AttemptedWhite PeopleYoung AdultConceptsMajor depressive episodeSubstance dependenceMDE subtypesDrug dependenceRelated clinical featuresPotential therapeutic implicationsSubstance use disordersAcademic medical centerGreater psychiatric severitySemi-Structured AssessmentClinical featuresDepressive episodeMajor depressionMedical CenterSecondary data analysisDepressive symptomsDiagnostic criteriaPsychiatric severityTherapeutic implicationsUse disordersSubtypesAnxiety disordersPsychiatric measuresCase-control genetic studyCommunity recruitment
2007
The Serotonin Transporter Genotype and Social Support and Moderation of Posttraumatic Stress Disorder and Depression in Hurricane-Exposed Adults
Kilpatrick DG, Koenen KC, Ruggiero KJ, Acierno R, Galea S, Resnick HS, Roitzsch J, Boyle J, Gelernter J. The Serotonin Transporter Genotype and Social Support and Moderation of Posttraumatic Stress Disorder and Depression in Hurricane-Exposed Adults. American Journal Of Psychiatry 2007, 164: 1693-1699. PMID: 17974934, DOI: 10.1176/appi.ajp.2007.06122007.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultDepressive Disorder, MajorDiagnostic and Statistical Manual of Mental DisordersDisastersFemaleFloridaGenetic VariationGenotypeHumansLife Change EventsLogistic ModelsMaleMiddle AgedPolymorphism, GeneticPsychiatric Status Rating ScalesRisk FactorsSerotonin Plasma Membrane Transport ProteinsSocial SupportStress Disorders, Post-TraumaticConceptsHigh hurricane exposurePosttraumatic stress disorderLow social supportMajor depressionLow-expression variantPostdisaster posttraumatic stress disorderSocial supportStress disorderHurricane exposureHigh-risk individualsDSM-IV diagnosisLow-risk individualsAdults ages 18Household probability sampleSubset of participantsOutcome measuresAdults 6Serotonin transporter genotypeSerotonin transporter geneAge 18DepressionDisaster exposureTransporter genotypeRiskStructured interviews
2003
Alleles of a Functional Serotonin Transporter Promoter Polymorphism Are Associated With Major Depression in Alcoholics
Nellissery M, Feinn RS, Covault J, Gelernter J, Anton RF, Pettinati H, Moak D, Mueller T, Kranzler HR. Alleles of a Functional Serotonin Transporter Promoter Polymorphism Are Associated With Major Depression in Alcoholics. Alcohol Clinical And Experimental Research 2003, 27: 1402-1408. PMID: 14506400, DOI: 10.1097/01.alc.0000085588.11073.bb.Peer-Reviewed Original ResearchMeSH KeywordsAdultAlcoholismAllelesBlack PeopleCarrier ProteinsChromosome MappingComorbidityDepressive Disorder, MajorFemaleGene FrequencyGenotypeHumansMaleMembrane GlycoproteinsMembrane Transport ProteinsMiddle AgedNerve Tissue ProteinsPhenotypePolymerase Chain ReactionPolymorphism, GeneticPromoter Regions, GeneticSerotonin Plasma Membrane Transport ProteinsWhite PeopleConceptsMajor depressionComorbid alcohol dependenceAlcohol dependenceFunctional serotonin transporter promoter polymorphismAfrican American patientsSubstance use disordersSerotonin transporter promoter polymorphismShort alleleTransporter promoter polymorphismSerotonin transporter proteinAntidepressant treatmentPatient groupAmerican patientsSerotonergic neurotransmissionDepressed alcoholicsMood disordersPromoter polymorphismUnipolar depressionUse disordersControl groupTreatment studiesFunctional polymorphismsGenetic predictorsSerotonin transporterWhole blood
1997
Possible association of a polymorphism of the tryptophan hydroxylase gene with suicidal behavior in depressed patients
Mann JJ, Malone KM, Nielsen DA, Goldman D, Erdos J, Gelernter J. Possible association of a polymorphism of the tryptophan hydroxylase gene with suicidal behavior in depressed patients. American Journal Of Psychiatry 1997, 154: 1451-1453. PMID: 9326831, DOI: 10.1176/ajp.154.10.1451.Peer-Reviewed Original Research