Featured Publications
Genome-wide association analyses of post-traumatic stress disorder and its symptom subdomains in the Million Veteran Program
Stein MB, Levey DF, Cheng Z, Wendt FR, Harrington K, Pathak GA, Cho K, Quaden R, Radhakrishnan K, Girgenti MJ, Ho YA, Posner D, Aslan M, Duman RS, Zhao H, Polimanti R, Concato J, Gelernter J. Genome-wide association analyses of post-traumatic stress disorder and its symptom subdomains in the Million Veteran Program. Nature Genetics 2021, 53: 174-184. PMID: 33510476, PMCID: PMC7972521, DOI: 10.1038/s41588-020-00767-x.Peer-Reviewed Original ResearchConceptsGenome-wide association analysisAssociation analysisMillion Veteran ProgramGenomic structural equation modelingSignificant lociGenetic varianceGene expressionDrug repositioning candidatesBiological coherenceVeteran ProgramMultiple testing correctionSymptom phenotypeLociRepositioning candidatesAfrican ancestryHeritabilityPhenotypeAncestryExpressionPTSD symptom factorsRegionSubdomainsEnrichmentGenome-wide association study of post-traumatic stress disorder reexperiencing symptoms in >165,000 US veterans
Gelernter J, Sun N, Polimanti R, Pietrzak R, Levey DF, Bryois J, Lu Q, Hu Y, Li B, Radhakrishnan K, Aslan M, Cheung KH, Li Y, Rajeevan N, Sayward F, Harrington K, Chen Q, Cho K, Pyarajan S, Sullivan PF, Quaden R, Shi Y, Hunter-Zinck H, Gaziano JM, Concato J, Zhao H, Stein MB. Genome-wide association study of post-traumatic stress disorder reexperiencing symptoms in >165,000 US veterans. Nature Neuroscience 2019, 22: 1394-1401. PMID: 31358989, PMCID: PMC6953633, DOI: 10.1038/s41593-019-0447-7.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesAssociation studiesHigh linkage disequilibrium regionLinkage disequilibrium regionWide association studyDisequilibrium regionBioinformatics analysisTranscriptomic profilesMillion Veteran ProgramChromosome 17Genetic risk factorsNew insightsUK Biobank dataReexperiencing of traumaStriatal medium spiny neuronsVeteran ProgramSignificant regionsCAMKVEuropean AmericansBiobank dataMedium spiny neuronsTCF4BiologyKANSL1African American cohort
2024
Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program
Verma A, Huffman J, Rodriguez A, Conery M, Liu M, Ho Y, Kim Y, Heise D, Guare L, Panickan V, Garcon H, Linares F, Costa L, Goethert I, Tipton R, Honerlaw J, Davies L, Whitbourne S, Cohen J, Posner D, Sangar R, Murray M, Wang X, Dochtermann D, Devineni P, Shi Y, Nandi T, Assimes T, Brunette C, Carroll R, Clifford R, Duvall S, Gelernter J, Hung A, Iyengar S, Joseph J, Kember R, Kranzler H, Kripke C, Levey D, Luoh S, Merritt V, Overstreet C, Deak J, Grant S, Polimanti R, Roussos P, Shakt G, Sun Y, Tsao N, Venkatesh S, Voloudakis G, Justice A, Begoli E, Ramoni R, Tourassi G, Pyarajan S, Tsao P, O'Donnell C, Muralidhar S, Moser J, Casas J, Bick A, Zhou W, Cai T, Voight B, Cho K, Gaziano J, Madduri R, Damrauer S, Liao K. Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program. Science 2024, 385: eadj1182. PMID: 39024449, DOI: 10.1126/science.adj1182.Peer-Reviewed Original ResearchConceptsMillion Veteran ProgramNon-European populationsVeteran ProgramGenetic architectureAtlas of genetic associationsVeterans Affairs Million Veteran ProgramVA Million Veteran ProgramGenomic risk lociGenome-wide associationHuman genetic studiesHealth disparitiesUnited States veteransCausal variantsRisk lociGenetic insightsGenetic studiesGenetic associationGenetic causeStates veteransDiverse populationsDisease factorsLack of inclusionLongitudinal studyParticipantsTraitsGenome-wide association study of the common retinal disorder epiretinal membrane: Significant risk loci in each of three American populations
Gelernter J, Levey D, Galimberti M, Harrington K, Zhou H, Adhikari K, Gupta P, Program V, Gaziano J, Eliott D, Stein M. Genome-wide association study of the common retinal disorder epiretinal membrane: Significant risk loci in each of three American populations. Cell Genomics 2024, 4: 100582. PMID: 38870908, PMCID: PMC11228954, DOI: 10.1016/j.xgen.2024.100582.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesMillion Veteran ProgramRisk lociAssociation studiesTrans-ancestry meta-analysisSignificant risk lociPathway enrichment analysisEpiretinal membraneTrans-ancestryGenome-wideMultiple traitsGenetic associationEnrichment analysisGene expressionEuropean AmericansLoss of visual acuityVeteran ProgramGenetic correlationsLociBiological mechanismsAmerican populationVisual acuityRetinal conditionsControl individualsRetinal surface
2023
Baseline platelet serotonin in a multi-site treatment study of depression in veterans administration patients: Distribution and effects of demographic variables and serotonin reuptake inhibitors
Anderson G, Ramsey C, Lynch K, Gelernter J, Oslin D. Baseline platelet serotonin in a multi-site treatment study of depression in veterans administration patients: Distribution and effects of demographic variables and serotonin reuptake inhibitors. Journal Of Affective Disorders 2023, 327: 368-377. PMID: 36754092, DOI: 10.1016/j.jad.2023.02.017.Peer-Reviewed Original ResearchConceptsReuptake inhibitorsVeterans Administration patientsTreatment studiesSubset of patientsNorepinephrine reuptake inhibitorsCross-sectional studyEffect of ageDose adjustmentAfrican American individualsDemographic variablesMean plateletDrug exposurePlatelet serotoninSerotonin valuesPatientsClinical implicationsHealth recordsMale groupSSRIsDepressionPlateletsEuropean AmericansInhibitorsSex differencesGroup means
2022
Effect of Pharmacogenomic Testing for Drug-Gene Interactions on Medication Selection and Remission of Symptoms in Major Depressive Disorder
Oslin DW, Lynch KG, Shih MC, Ingram EP, Wray LO, Chapman SR, Kranzler HR, Gelernter J, Pyne JM, Stone A, DuVall SL, Lehmann LS, Thase ME, Aslam M, Batki S, Bjork J, Blow F, Brenner L, Chen P, Desai S, Dieperink E, Fears S, Fuller M, Goodman C, Graham D, Haas G, Hamner M, Helstrom A, Hurley R, Icardi M, Jurjus G, Kilbourne A, Kreyenbuhl J, Lache D, Lieske S, Lynch J, Meyer L, Montalvo C, Muralidhar S, Ostacher M, Paschall G, Pfeiffer P, Prieto S, Przygodzki R, Ranganathan M, Rodriguez-Suarez M, Roggenkamp H, Schichman S, Schneeweis J, Simonetti J, Steinhauer S, Suppes T, Umbert M, Vassy J, Voora D, Wiechers I, Wood A. Effect of Pharmacogenomic Testing for Drug-Gene Interactions on Medication Selection and Remission of Symptoms in Major Depressive Disorder. JAMA 2022, 328: 151-161. PMID: 35819423, PMCID: PMC9277497, DOI: 10.1001/jama.2022.9805.Peer-Reviewed Original ResearchConceptsMajor depressive disorderPatient Health Questionnaire-9Usual care groupUsual carePharmacogenomic testingDrug-gene interactionsRemission rateMedication selectionCare groupDepressive disorderVeterans Affairs Medical CenterActive substance use disorderCo-primary outcomesPrescription of medicationsBetter clinical outcomesProportion of prescriptionsRemission of symptomsSubstance use disordersEligible patientsWeek 24Effective antidepressantSingle antidepressantClinical outcomesInitial treatmentQuestionnaire-9
2020
Association of OPRM1 Functional Coding Variant With Opioid Use Disorder
Zhou H, Rentsch CT, Cheng Z, Kember RL, Nunez YZ, Sherva RM, Tate JP, Dao C, Xu K, Polimanti R, Farrer LA, Justice AC, Kranzler HR, Gelernter J. Association of OPRM1 Functional Coding Variant With Opioid Use Disorder. JAMA Psychiatry 2020, 77: 1072-1080. PMID: 32492095, PMCID: PMC7270886, DOI: 10.1001/jamapsychiatry.2020.1206.Peer-Reviewed Original ResearchConceptsOpioid use disorderUse disordersMendelian randomization analysisAfrican American individualsMAIN OUTCOMEFunctional coding variantSignificant associationCausal associationRandomization analysisElectronic health record dataCurrent opioid crisisAmerican individualsHealth record dataCognitive performanceInternational Statistical ClassificationRelated Health ProblemsPotential causal associationAmerican controlsEuropean American controlsAfrican-American controlsCoding variantBuprenorphine treatmentOUD diagnosisTobacco smokingNinth RevisionAttachment Style Moderates Polygenic Risk for Posttraumatic Stress in United States Military Veterans: Results From the National Health and Resilience in Veterans Study
Tamman AJF, Wendt FR, Pathak GA, Krystal JH, Montalvo-Ortiz JL, Southwick SM, Sippel LM, Gelernter J, Polimanti R, Pietrzak RH. Attachment Style Moderates Polygenic Risk for Posttraumatic Stress in United States Military Veterans: Results From the National Health and Resilience in Veterans Study. Biological Psychiatry 2020, 89: 878-887. PMID: 33276944, DOI: 10.1016/j.biopsych.2020.09.018.Peer-Reviewed Original ResearchA genome-wide association study of cocaine use disorder accounting for phenotypic heterogeneity and gene–environment interaction
Sun J, Kranzler HR, Gelernter J, Bi J. A genome-wide association study of cocaine use disorder accounting for phenotypic heterogeneity and gene–environment interaction. Journal Of Psychiatry And Neuroscience 2020, 45: 34-44. PMID: 31490055, PMCID: PMC6919916, DOI: 10.1503/jpn.180098.Peer-Reviewed Original ResearchConceptsGenetic lociGenome-wide association testsPhenotypic heterogeneityNew genetic lociGenetic variantsWide association studyGene-environment interplayNovel genetic variantsHigh heritability estimatesSignificant genomeReplication sampleSingle nucleotide polymorphismsGenetic variationAssociation studiesLociNucleotide polymorphismsAssociation TestHeritability estimatesGene-environment interactionsReplication resultsCluster analysisEnvironmental factorsTRAK2GenomeDiscovery phase
2019
Epigenome‐Wide DNA Methylation Association Analysis Identified Novel Loci in Peripheral Cells for Alcohol Consumption Among European American Male Veterans
Xu K, Montalvo‐Ortiz J, Zhang X, Southwick SM, Krystal JH, Pietrzak RH, Gelernter J. Epigenome‐Wide DNA Methylation Association Analysis Identified Novel Loci in Peripheral Cells for Alcohol Consumption Among European American Male Veterans. Alcohol Clinical And Experimental Research 2019, 43: 2111-2121. PMID: 31386212, PMCID: PMC9377208, DOI: 10.1111/acer.14168.Peer-Reviewed Original ResearchConceptsEpigenome-wide association studiesDNA methylationCpG sitesSignificant CpG sitesHigh-density methylation arraysNovel DNA methylation sitesNew CpG sitesDNA methylation sitesEpigenome-wide DNA methylationAmino acid transportIndividual CpG sitesGene lengthPeripheral cellsNovel lociDNA sitesKEGG databaseMethylation sitesEnrichment analysisMethylation arraysAssociation studiesAssociation analysisGenesMethylationAcid transportFalse discovery rateApolipoprotein E gene polymorphism, posttraumatic stress disorder, and cognitive function in older U.S. veterans: Results from the National Health and Resilience in Veterans Study
Averill LA, Abdallah CG, Levey DF, Han S, Harpaz‐Rotem I, Kranzler HR, Southwick SM, Krystal JH, Gelernter J, Pietrzak RH. Apolipoprotein E gene polymorphism, posttraumatic stress disorder, and cognitive function in older U.S. veterans: Results from the National Health and Resilience in Veterans Study. Depression And Anxiety 2019, 36: 834-845. PMID: 31385647, DOI: 10.1002/da.22912.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderExecutive functionCognitive functioningStress disorderΕ4 carrier statusΕ4 carriersVeterans StudyCognitive dysfunctionAttention/concentrationGreater cognitive difficultiesLower cognitive functioningOlder U.S. veteransΕ4 allele carrier statusPerseverative errorsCognitive difficultiesReplication sampleCarrier statusCognitive functionImportance of assessingNational HealthCognitive declinePredictive effectApolipoprotein E gene polymorphismE gene polymorphismΕ4 allele carriersGenome‐wide scan identifies opioid overdose risk locus close to MCOLN1
Cheng Z, Yang B, Zhou H, Nunez Y, Kranzler HR, Gelernter J. Genome‐wide scan identifies opioid overdose risk locus close to MCOLN1. Addiction Biology 2019, 25: e12811. PMID: 31362332, PMCID: PMC7485539, DOI: 10.1111/adb.12811.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesMucolipin-1Expression profilesGenome-wide significant signalsAssociation studiesPost-GWAS analysisWide association studyDrug repositioning analysisCation channel activityFunctional categoriesConnectivity Map databaseDrug targetsRisk genesGenesChannel activityPatatin-like phospholipaseNetwork analysisPNPLA6Significant signalEuropean AmericansGenome-Wide Meta-Analyses of FTND and TTFC Phenotypes
Chen J, Loukola A, Gillespie NA, Peterson R, Jia P, Riley B, Maes H, Dick DM, Kendler KS, Damaj MI, Miles MF, Zhao Z, Li MD, Vink JM, Minica CC, Willemsen G, Boomsma DI, Qaiser B, Madden PAF, Korhonen T, Jousilahti P, Hällfors J, Gelernter J, Kranzler HR, Sherva R, Farrer L, Maher B, Vanyukov M, Taylor M, Ware JJ, Munafò MR, Lutz SM, Hokanson JE, Gu F, Landi MT, Caporaso NE, Hancock DB, Gaddis NC, Baker TB, Bierut LJ, Johnson EO, Chenoweth M, Lerman C, Tyndale R, Kaprio J, Chen X. Genome-Wide Meta-Analyses of FTND and TTFC Phenotypes. Nicotine & Tobacco Research 2019, 22: 900-909. PMID: 31294817, PMCID: PMC7249921, DOI: 10.1093/ntr/ntz099.Peer-Reviewed Original ResearchConceptsGenome-Wide Meta-AnalysisGene-based analysisChemokine signaling pathwaysGenetic architectureActin cytoskeletonNew lociReceptor recyclingMAPK signalingPathway interactionsBiological pathwaysSignaling pathwaysAxon guidanceNovel pathwayPhenotypeNovel candidatesEuropean ancestryPathwayReplication sampleNetwork analysisReplicationIno80CCytoskeletonCOPB2EndocytosisSORBS2Genome‐wide analyses of psychological resilience in U.S. Army soldiers
Stein MB, Choi KW, Jain S, Campbell‐Sills L, Chen C, Gelernter J, He F, Heeringa SG, Maihofer AX, Nievergelt C, Nock MK, Ripke S, Sun X, Kessler RC, Smoller JW, Ursano RJ. Genome‐wide analyses of psychological resilience in U.S. Army soldiers. American Journal Of Medical Genetics Part B Neuropsychiatric Genetics 2019, 180: 310-319. PMID: 31081985, PMCID: PMC6551278, DOI: 10.1002/ajmg.b.32730.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesGenome-wide significant lociGenome-wide significant associationGenome-wide analysisCommon variant heritabilityGenome-wide significanceIntergenic regionSecond geneSignificant lociGenetic basisMolecular basisKinase 2Association studiesMember 5Genetic determinantsDoublecortin familyLociBiological basisPolygenic risk scoresNew avenuesValidation of an Electronic Medical Record–Based Algorithm for Identifying Posttraumatic Stress Disorder in U.S. Veterans
Harrington KM, Quaden R, Stein MB, Honerlaw JP, Cissell S, Pietrzak RH, Zhao H, Radhakrishnan K, Aslan M, Gaziano JM, Concato J, Gagnon DR, Gelernter J, Cho K, Program O. Validation of an Electronic Medical Record–Based Algorithm for Identifying Posttraumatic Stress Disorder in U.S. Veterans. Journal Of Traumatic Stress 2019, 32: 226-237. PMID: 31009556, PMCID: PMC6699164, DOI: 10.1002/jts.22399.Peer-Reviewed Original ResearchGenome-wide Association Study of Maximum Habitual Alcohol Intake in >140,000 U.S. European and African American Veterans Yields Novel Risk Loci
Gelernter J, Sun N, Polimanti R, Pietrzak RH, Levey DF, Lu Q, Hu Y, Li B, Radhakrishnan K, Aslan M, Cheung KH, Li Y, Rajeevan N, Sayward F, Harrington K, Chen Q, Cho K, Honerlaw J, Pyarajan S, Lencz T, Quaden R, Shi Y, Hunter-Zinck H, Gaziano JM, Kranzler HR, Concato J, Zhao H, Stein MB, Program D, Program M. Genome-wide Association Study of Maximum Habitual Alcohol Intake in >140,000 U.S. European and African American Veterans Yields Novel Risk Loci. Biological Psychiatry 2019, 86: 365-376. PMID: 31151762, PMCID: PMC6919570, DOI: 10.1016/j.biopsych.2019.03.984.Peer-Reviewed Original ResearchConceptsAdditional genome-wide significant lociRisk lociWide association study (GWAS) analysisAssociation studiesGenome-wide significant lociGenome-wide association studiesGenetic correlationsWide association studyNovel risk lociAlcohol-related traitsStrong statistical supportSmoking-related traitsAdditional genomesSignificant lociPancreatic delta cellsChromosome 4Chromosome 11Protein productsChromosome 8Quantitative phenotypesMillion Veteran ProgramVeterans Affairs Million Veteran ProgramLociCell typesChromosome 17Genomewide Study of Epigenetic Biomarkers of Opioid Dependence in European- American Women
Montalvo-Ortiz JL, Cheng Z, Kranzler HR, Zhang H, Gelernter J. Genomewide Study of Epigenetic Biomarkers of Opioid Dependence in European- American Women. Scientific Reports 2019, 9: 4660. PMID: 30874594, PMCID: PMC6420601, DOI: 10.1038/s41598-019-41110-7.Peer-Reviewed Original ResearchConceptsEpigenome-wide association studiesEpigenetic mechanismsAssociation studiesAssociation analysisCpG sitesFirst epigenome-wide association studyGenome-wide association studiesPrevious genome-wide association studyCandidate gene approachChromatin remodelingDNA bindingGene approachGenomewide studiesDNA methylation ageCell survivalEpigenetic biomarkersRisk variantsPopulation stratificationMethylation ageGenesCell projectionsOpioid dependenceNovel peripheral biomarkersEuropean American womenCell proportionGenomics of posttraumatic stress disorder in veterans: Methods and rationale for Veterans Affairs Cooperative Study #575B
Radhakrishnan K, Aslan M, Harrington KM, Pietrzak RH, Huang G, Muralidhar S, Cho K, Quaden R, Gagnon D, Pyarajan S, Sun N, Zhao H, Gaziano M, Concato J, Stein MB, Gelernter J. Genomics of posttraumatic stress disorder in veterans: Methods and rationale for Veterans Affairs Cooperative Study #575B. International Journal Of Methods In Psychiatric Research 2019, 28: e1767. PMID: 30767326, PMCID: PMC6877159, DOI: 10.1002/mpr.1767.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAged, 80 and overAlgorithmsCase-Control StudiesFemaleGenetic Predisposition to DiseaseGenomicsHumansInterviews as TopicMaleMiddle AgedPolymorphism, Single NucleotidePsychiatric Status Rating ScalesStress Disorders, Post-TraumaticSurveys and QuestionnairesUnited StatesUnited States Department of Veterans AffairsVeteransYoung AdultGenetic associations with suicide attempt severity and genetic overlap with major depression
Levey DF, Polimanti R, Cheng Z, Zhou H, Nuñez YZ, Jain S, He F, Sun X, Ursano RJ, Kessler RC, Smoller JW, Stein MB, Kranzler HR, Gelernter J. Genetic associations with suicide attempt severity and genetic overlap with major depression. Translational Psychiatry 2019, 9: 22. PMID: 30655502, PMCID: PMC6336846, DOI: 10.1038/s41398-018-0340-2.Peer-Reviewed Original ResearchConceptsGWS associationsGenome-wide significant signalsCircadian clock regulationWide association studyGenetic overlapCatabolism of tyrosineClock regulationFirst GWASSignificant genetic overlapDiscovery GWASChromosome 12Large GWASMolecular mechanismsAssociation studiesChromosome 15Chromosome 18Genetic influencesDiscovery sampleGenetic associationSuicide attempt severityReplication analysisGWASAnaerobic energy productionGenetic risk factorsPolygenic risk scores
2018
Adverse 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 sampleChildrenRisk