2023
Polygenic risk score for problematic alcohol use predicts heavy drinking and alcohol use disorder symptoms in young adulthood after accounting for adolescent alcohol use and parental alcohol use disorder
Wang F, Hicks B, Zhou H, Kranzler H, Gelernter J, Zucker R. Polygenic risk score for problematic alcohol use predicts heavy drinking and alcohol use disorder symptoms in young adulthood after accounting for adolescent alcohol use and parental alcohol use disorder. Drug And Alcohol Dependence 2023, 248: 109909. PMID: 37163864, PMCID: PMC11013565, DOI: 10.1016/j.drugalcdep.2023.109909.Peer-Reviewed Original Research
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 smoking
2020
Polygenic risk for autism spectrum disorder associates with anger recognition in a neurodevelopment-focused phenome-wide scan of unaffected youths from a population-based cohort
Wendt FR, Carvalho CM, Pathak GA, Gelernter J, Polimanti R. Polygenic risk for autism spectrum disorder associates with anger recognition in a neurodevelopment-focused phenome-wide scan of unaffected youths from a population-based cohort. PLOS Genetics 2020, 16: e1009036. PMID: 32941431, PMCID: PMC7523983, DOI: 10.1371/journal.pgen.1009036.Peer-Reviewed Original ResearchDissecting the genetic association of C-reactive protein with PTSD, traumatic events, and social support
Muniz Carvalho C, Wendt FR, Maihofer AX, Stein DJ, Stein MB, Sumner JA, Hemmings SMJ, Nievergelt CM, Koenen KC, Gelernter J, Belangero SI, Polimanti R. Dissecting the genetic association of C-reactive protein with PTSD, traumatic events, and social support. Neuropsychopharmacology 2020, 46: 1071-1077. PMID: 32179874, PMCID: PMC8115274, DOI: 10.1038/s41386-020-0655-6.Peer-Reviewed Original Research
2018
Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder
Demontis D, Walters RK, Martin J, Mattheisen M, Als TD, Agerbo E, Baldursson G, Belliveau R, Bybjerg-Grauholm J, Bækvad-Hansen M, Cerrato F, Chambert K, Churchhouse C, Dumont A, Eriksson N, Gandal M, Goldstein JI, Grasby KL, Grove J, Gudmundsson OO, Hansen CS, Hauberg ME, Hollegaard MV, Howrigan DP, Huang H, Maller JB, Martin AR, Martin NG, Moran J, Pallesen J, Palmer DS, Pedersen CB, Pedersen MG, Poterba T, Poulsen JB, Ripke S, Robinson EB, Satterstrom FK, Stefansson H, Stevens C, Turley P, Walters GB, Won H, Wright MJ, Andreassen O, Asherson P, Burton C, Boomsma D, Cormand B, Dalsgaard S, Franke B, Gelernter J, Geschwind D, Hakonarson H, Haavik J, Kranzler H, Kuntsi J, Langley K, Lesch K, Middeldorp C, Reif A, Rohde L, Roussos P, Schachar R, Sklar P, Sonuga-Barke E, Sullivan P, Thapar A, Tung J, Waldman I, Medland S, Stefansson K, Nordentoft M, Hougaard D, Werge T, Mors O, Mortensen P, Daly M, Faraone S, Børglum A, Neale B. Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder. Nature Genetics 2018, 51: 63-75. PMID: 30478444, PMCID: PMC6481311, DOI: 10.1038/s41588-018-0269-7.Peer-Reviewed Original ResearchConceptsGenome-wide significant risk lociFunction intolerant genesGenome-wide associationSignificant risk lociGenome-wide significanceAttention-deficit/hyperactivity disorderCommon genetic variantsGenomic regionsIntolerant genesIndependent lociRegulatory marksHeritable traitRisk lociDeficit/hyperactivity disorderGenetic variantsGenetic overlapStudy-specific differencesLociHyperactivity disorderImportant new informationUnderlying biologyChildhood behavioral disordersVariantsStrong concordanceGWASAdverse Childhood Experiences, Epigenetic Measures, and Obesity in Youth
Kaufman J, Montalvo-Ortiz JL, Holbrook H, O'Loughlin K, Orr C, Kearney C, Yang BZ, Wang T, Zhao H, Althoff R, Garavan H, Gelernter J, Hudziak J. Adverse Childhood Experiences, Epigenetic Measures, and Obesity in Youth. The Journal Of Pediatrics 2018, 202: 150-156.e3. PMID: 30177354, PMCID: PMC6513669, DOI: 10.1016/j.jpeds.2018.06.051.Peer-Reviewed Original ResearchConceptsBody mass indexAdverse childhood experiencesMass indexIndices of obesityAssessment of obesityChildhood experiencesFuture longitudinal studiesObesity riskHealth burdenPsychiatric outcomesSecond cohortObesityNovel interventionsCohortEarly adversityCross-sectional measuresEpigenetic predictorsLongitudinal studySaliva DNAEpigenetic measuresWhole genome testingDiscovery sampleReplication sampleChildrenRiskMethylation in OTX2 and related genes, maltreatment, and depression in children
Kaufman J, Wymbs NF, Montalvo-Ortiz JL, Orr C, Albaugh MD, Althoff R, O’Loughlin K, Holbrook H, Garavan H, Kearney C, Yang BZ, Zhao H, Peña C, Nestler EJ, Lee RS, Mostofsky S, Gelernter J, Hudziak J. Methylation in OTX2 and related genes, maltreatment, and depression in children. Neuropsychopharmacology 2018, 43: 2204-2211. PMID: 30089883, PMCID: PMC6135753, DOI: 10.1038/s41386-018-0157-y.Peer-Reviewed Original ResearchConceptsMouse modelStress-related depressive disordersResting-state functional connectivity dataResting-state functional MRI dataDepressive-like behaviorEarly life stressSubset of childrenDNA specimensMedial frontal cortexPeripheral markersMeasures of depressionHomeobox 2 geneSubcallosal gyrusFunctional connectivity dataDepressive disorderFrontal cortexChild adversityMultiple molecular toolsFunctional MRI dataFrontal poleLarger studyFunctional connectivitySaliva samplesBilateral regionsUnbiased transcriptomics
2017
Genome-Wide Association Studies of a Broad Spectrum of Antisocial Behavior
Tielbeek JJ, Johansson A, Polderman TJC, Rautiainen MR, Jansen P, Taylor M, Tong X, Lu Q, Burt AS, Tiemeier H, Viding E, Plomin R, Martin NG, Heath AC, Madden PAF, Montgomery G, Beaver KM, Waldman I, Gelernter J, Kranzler HR, Farrer LA, Perry JRB, Munafò M, LoParo D, Paunio T, Tiihonen J, Mous SE, Pappa I, de Leeuw C, Watanabe K, Hammerschlag AR, Salvatore JE, Aliev F, Bigdeli TB, Dick D, Faraone SV, Popma A, Medland SE, Posthuma D. Genome-Wide Association Studies of a Broad Spectrum of Antisocial Behavior. JAMA Psychiatry 2017, 74: 1242-1250. PMID: 28979981, PMCID: PMC6309228, DOI: 10.1001/jamapsychiatry.2017.3069.Peer-Reviewed Original ResearchConceptsNovel genetic risk variantsSingle nucleotide polymorphism-based heritabilityGenome-wide association studiesGenome-wide association dataCausal genetic variantsGenome-wide genotypesPolygenic risk score analysisGenetic architectureGenetic risk variantsInverse genetic correlationPromising lociAssociation studiesBiological pathwaysPleiotropic associationsQuantitative phenotypesGenetic correlationsPsychiatric traitsAssociation dataGenetic effectsRisk variantsRisk score analysisGenetic variantsGenetic originDiscovery sampleTraits
2015
Association of the OPRM1 Variant rs1799971 (A118G) with Non-Specific Liability to Substance Dependence in a Collaborative de novo Meta-Analysis of European-Ancestry Cohorts
Schwantes-An TH, Zhang J, Chen LS, Hartz SM, Culverhouse RC, Chen X, Coon H, Frank J, Kamens HM, Konte B, Kovanen L, Latvala A, Legrand LN, Maher BS, Melroy WE, Nelson EC, Reid MW, Robinson JD, Shen PH, Yang BZ, Andrews JA, Aveyard P, Beltcheva O, Brown SA, Cannon DS, Cichon S, Corley RP, Dahmen N, Degenhardt L, Foroud T, Gaebel W, Giegling I, Glatt SJ, Grucza RA, Hardin J, Hartmann AM, Heath AC, Herms S, Hodgkinson CA, Hoffmann P, Hops H, Huizinga D, Ising M, Johnson EO, Johnstone E, Kaneva RP, Kendler KS, Kiefer F, Kranzler HR, Krauter KS, Levran O, Lucae S, Lynskey MT, Maier W, Mann K, Martin NG, Mattheisen M, Montgomery GW, Müller-Myhsok B, Murphy MF, Neale MC, Nikolov MA, Nishita D, Nöthen MM, Nurnberger J, Partonen T, Pergadia ML, Reynolds M, Ridinger M, Rose RJ, Rouvinen-Lagerström N, Scherbaum N, Schmäl C, Soyka M, Stallings MC, Steffens M, Treutlein J, Tsuang M, Wall TL, Wodarz N, Yuferov V, Zill P, Bergen AW, Chen J, Cinciripini PM, Edenberg HJ, Ehringer MA, Ferrell RE, Gelernter J, Goldman D, Hewitt JK, Hopfer CJ, Iacono WG, Kaprio J, Kreek MJ, Kremensky IM, Madden PA, McGue M, Munafò MR, Philibert RA, Rietschel M, Roy A, Rujescu D, Saarikoski ST, Swan GE, Todorov AA, Vanyukov MM, Weiss RB, Bierut LJ, Saccone NL. Association of the OPRM1 Variant rs1799971 (A118G) with Non-Specific Liability to Substance Dependence in a Collaborative de novo Meta-Analysis of European-Ancestry Cohorts. Behavior Genetics 2015, 46: 151-169. PMID: 26392368, PMCID: PMC4752855, DOI: 10.1007/s10519-015-9737-3.Peer-Reviewed Original ResearchConceptsSubstance dependenceModest protective effectDSM-IV alcoholOpioid receptor geneLight smokingProtective effectNicotine dependenceAddiction liabilityDifferent addictive substancesG alleleMeta-AnalysisCocaine dependenceRs1799971Addictive substancesHuman genetic studiesReceptor genePotential functional significanceEuropean ancestry cohortsOPRM1Substance dependence riskSimilar effectsEuropean ancestry subjectsFunctional significanceAddictive behaviorsRiskThe Research Domain Criteria (RDoC) Project and Studies of Risk and Resilience in Maltreated Children
Kaufman J, Gelernter J, Hudziak JJ, Tyrka AR, Coplan JD. The Research Domain Criteria (RDoC) Project and Studies of Risk and Resilience in Maltreated Children. Journal Of The American Academy Of Child & Adolescent Psychiatry 2015, 54: 617-625. PMID: 26210330, PMCID: PMC4515569, DOI: 10.1016/j.jaac.2015.06.001.Peer-Reviewed Original ResearchConceptsResearch Domain Criteria projectNeural circuitsSubset of patientsRelevant animal modelsOnset of psychopathologyStress-related mechanismsClinical studiesStandard interventionAnimal modelsClinical implicationsMental disordersMaltreated childrenNeural circuitryTranslational researchPrecision medicinePsychiatric nomenclaturePatientsChildrenRDoC projectRDoC frameworkNeurobiological measuresRDoC initiativeRiskUltimate long-term goalStudy of risk
2014
The Joint Effects of ADH1B Variants and Childhood Adversity on Alcohol Related Phenotypes in African‐American and European‐American Women and Men
Sartor CE, Wang Z, Xu K, Kranzler HR, Gelernter J. The Joint Effects of ADH1B Variants and Childhood Adversity on Alcohol Related Phenotypes in African‐American and European‐American Women and Men. Alcohol Clinical And Experimental Research 2014, 38: 2907-2914. PMID: 25410943, PMCID: PMC4445128, DOI: 10.1111/acer.12572.Peer-Reviewed Original ResearchConceptsChildhood adversityAllele carriersEA menAlcohol use disorder symptomsAlcohol phenotypesRisk factorsAA womenProtective effectADH1B rs1229984Psychiatric outcomesEA womenEuropean American womenOrdinal regression analysisProtective allelesAlcohol dependenceAUD symptomsSubstance dependenceSingle nucleotide polymorphismsDisorder symptomsADH1B variantsAlcohol problemsWomenMenRegression analysisSignificant main effectEvaluating the role of a galanin enhancer genotype on a range of metabolic, depressive and addictive phenotypes
Richardson TG, Minica C, Heron J, Tavare J, MacKenzie A, Day I, Lewis G, Hickman M, Vink JM, Gelernter J, Kranzler HR, Farrer LA, Munafò M, Wynick D. Evaluating the role of a galanin enhancer genotype on a range of metabolic, depressive and addictive phenotypes. American Journal Of Medical Genetics Part B Neuropsychiatric Genetics 2014, 165: 654-664. PMID: 25228436, PMCID: PMC4388908, DOI: 10.1002/ajmg.b.32270.Peer-Reviewed Original ResearchConceptsRat hypothalamic neuronsAvon Longitudinal StudyGalaninergic systemGalanin expressionNeuropeptide galaninHypothalamic neuronsClinical dataChild CohortEnhancer region upstreamGG alleleCannabis usageYoung adultsCA alleleLongitudinal studyPathological functionsTransfection studiesInitial findingsGalaninCohortNeuronsChild Abuse, Depression, and Methylation in Genes Involved With Stress, Neural Plasticity, and Brain Circuitry
Weder N, Zhang H, Jensen K, Yang BZ, Simen A, Jackowski A, Lipschitz D, Douglas-Palumberi H, Ge M, Perepletchikova F, O'Loughlin K, Hudziak JJ, Gelernter J, Kaufman J. Child Abuse, Depression, and Methylation in Genes Involved With Stress, Neural Plasticity, and Brain Circuitry. Journal Of The American Academy Of Child & Adolescent Psychiatry 2014, 53: 417-424.e5. PMID: 24655651, PMCID: PMC4126411, DOI: 10.1016/j.jaac.2013.12.025.Peer-Reviewed Original ResearchConceptsTubulin Polymerization Promoting ProteinCandidate genesEpigenetic changesMethylation sitesGenome-wide methylation studyMultiple methylation sitesK BeadChip arraySaliva-derived DNAEpigenetic mechanismsK BeadChipBeadChip arrayEpigenetic markersStress responseMethylation studiesCpG sitesGenesNeural circuitry developmentMethylationId-3Whole genome testingNeural plasticityGRIN1Genome testingPlasticityGlutamate receptors
2013
Rate of progression from first use to dependence on cocaine or opioids: A cross-substance examination of associated demographic, psychiatric, and childhood risk factors
Sartor CE, Kranzler HR, Gelernter J. Rate of progression from first use to dependence on cocaine or opioids: A cross-substance examination of associated demographic, psychiatric, and childhood risk factors. Addictive Behaviors 2013, 39: 473-479. PMID: 24238782, PMCID: PMC3855905, DOI: 10.1016/j.addbeh.2013.10.021.Peer-Reviewed Original ResearchMeSH KeywordsAdultAge of OnsetAgedAlcohol-Related DisordersBehavior, AddictiveCase-Control StudiesChildChild AbuseCluster AnalysisCocaine-Related DisordersConnecticutCross-Sectional StudiesDiagnosis, Dual (Psychiatry)Disease ProgressionFemaleHumansInterviews as TopicLogistic ModelsMaleMental DisordersMiddle AgedOpioid-Related DisordersPennsylvaniaRisk FactorsSocial EnvironmentSocioeconomic FactorsSouth CarolinaTime FactorsConceptsChildhood risk factorsOpioid dependenceOpioid-dependent participantsRisk factorsCocaine dependenceDependent participantsImportant public health goalRate of progressionPublic health goalsLogistic regression modelsBlack/African AmericanChildhood physical abuseOrdinal logistic regression modelsCocaine-dependent participantsMean ageSlow progressionElevated riskAssociated demographicPsychiatric disordersMulti-site studyDependence diagnosisGreater riskHealth goalsSubstance dependenceConduct disorderChild Abuse and Epigenetic Mechanisms of Disease Risk
Yang BZ, Zhang H, Ge W, Weder N, Douglas-Palumberi H, Perepletchikova F, Gelernter J, Kaufman J. Child Abuse and Epigenetic Mechanisms of Disease Risk. American Journal Of Preventive Medicine 2013, 44: 101-107. PMID: 23332324, PMCID: PMC3758252, DOI: 10.1016/j.amepre.2012.10.012.Peer-Reviewed Original Research
2012
Serotonin transporter 5‐HTTLPR genotype moderates the effects of childhood adversity on posttraumatic stress disorder risk: A replication study
Xie P, Kranzler HR, Farrer L, Gelernter J. Serotonin transporter 5‐HTTLPR genotype moderates the effects of childhood adversity on posttraumatic stress disorder risk: A replication study. American Journal Of Medical Genetics Part B Neuropsychiatric Genetics 2012, 159B: 644-652. PMID: 22693124, PMCID: PMC3428016, DOI: 10.1002/ajmg.b.32068.Peer-Reviewed Original Research
2011
Genetic associations with performance on a behavioral measure of distress intolerance
Amstadter AB, Daughters SB, MacPherson L, Reynolds EK, Danielson CK, Wang F, Potenza MN, Gelernter J, Lejuez CW. Genetic associations with performance on a behavioral measure of distress intolerance. Journal Of Psychiatric Research 2011, 46: 87-94. PMID: 22024485, PMCID: PMC3687355, DOI: 10.1016/j.jpsychires.2011.09.017.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentCatechol O-MethyltransferaseChildChi-Square DistributionDistrict of ColumbiaFemaleGene FrequencyGenetic Association StudiesGenotypeHumansLongitudinal StudiesMaleMood DisordersPolymorphism, Single NucleotidePsychiatric Status Rating ScalesRegression AnalysisRisk-TakingSerotonin Plasma Membrane Transport ProteinsConceptsEmotion regulation difficultiesDistress intoleranceBehavioral measuresPoor psychological functioningAdolescent risk behaviorsDistress tolerancePsychological functioningLarger longitudinal studyVal allele carriersYear old youthMet homozygotesEmotional abuseBehavioral indicatorsBehavioral assessmentLongitudinal studyGenetic influencesCandidate genetic polymorphismsTaskYouthDistressExploratory analysisRisk behaviorsEmpirical evidencePrior studiesDifficultiesA CRHR1 haplotype moderates the effect of adverse childhood experiences on lifetime risk of major depressive episode in African‐American women
Kranzler HR, Feinn R, Nelson EC, Covault J, Anton RF, Farrer L, Gelernter J. A CRHR1 haplotype moderates the effect of adverse childhood experiences on lifetime risk of major depressive episode in African‐American women. American Journal Of Medical Genetics Part B Neuropsychiatric Genetics 2011, 156: 960-968. PMID: 21998007, PMCID: PMC3227028, DOI: 10.1002/ajmg.b.31243.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAlcohol DrinkingBlack or African AmericanChildChild AbuseDepressionDepressive Disorder, MajorFemaleGene FrequencyGenetic Predisposition to DiseaseHaplotypesHumansMiddle AgedPolymorphism, Single NucleotideReceptors, Corticotropin-Releasing HormoneStress, PsychologicalSubstance-Related DisordersConceptsMajor depressive episodeAdverse childhood experiencesRisk of depressionTAT haplotypeAlcohol dependenceDepressive episodeLifetime riskAA womenCorticotropin-releasing hormone type 1 receptorOdds of MDERisk of MDELifetime substance use disorderType 1 receptorSubstance use disordersAfrican AmericansAfrican American womenChildhood experiencesDepression riskThree-SNP haplotypeAD riskUse disordersAdult depressionAlcohol consumptionCRHR1 haplotypeCRHR15-HTTLPR as a potential moderator of the effects of adverse childhood experiences on risk of antisocial personality disorder
Douglas K, Chan G, Gelernter J, Arias AJ, Anton RF, Poling J, Farrer L, Kranzler HR. 5-HTTLPR as a potential moderator of the effects of adverse childhood experiences on risk of antisocial personality disorder. Psychiatric Genetics 2011, 21: 240-248. PMID: 21399568, PMCID: PMC3119731, DOI: 10.1097/ypg.0b013e3283457c15.Peer-Reviewed Original ResearchEmpirically derived subtypes of opioid use and related behaviors
Chan G, Gelernter J, Oslin D, Farrer L, Kranzler HR. Empirically derived subtypes of opioid use and related behaviors. Addiction 2011, 106: 1146-1154. PMID: 21306596, PMCID: PMC3164489, DOI: 10.1111/j.1360-0443.2011.03390.x.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAge of OnsetAgedAnalgesics, OpioidChildCluster AnalysisComorbidityDiagnostic and Statistical Manual of Mental DisordersFamily HealthFemaleGenetic Association StudiesGenetic Predisposition to DiseaseGenotypeHumansInterview, PsychologicalMaleMental DisordersMiddle AgedOpioid-Related DisordersPhenotypePrevalenceSiblingsSubstance Abuse, IntravenousUnited StatesYoung AdultConceptsOpioid usePsychiatric disordersHomogeneous subtypesRelated behaviorsSemi-Structured AssessmentGeneral community sampleOpioid dependenceMedical historyPrevalence ratesCocaine dependenceDrug dependenceSubtypesParticipant demographicsSubstance useCase-control genetic studyDemographicsDisordersCommunity sampleGenetic studies