Featured Publications
Genome-wide association studies and cross-population meta-analyses investigating short and long sleep duration
Austin-Zimmerman I, Levey D, Giannakopoulou O, Deak J, Galimberti M, Adhikari K, Zhou H, Denaxas S, Irizar H, Kuchenbaecker K, McQuillin A, Concato J, Buysse D, Gaziano J, Gottlieb D, Polimanti R, Stein M, Bramon E, Gelernter J. Genome-wide association studies and cross-population meta-analyses investigating short and long sleep duration. Nature Communications 2023, 14: 6059. PMID: 37770476, PMCID: PMC10539313, DOI: 10.1038/s41467-023-41249-y.Peer-Reviewed Original ResearchConceptsAssociation studiesGenome-wide association studiesGenetic correlationsWide association studyLinkage disequilibrium scorePositive genetic correlationSleep traitsIndependent lociMillion Veteran ProgramTraitsAncestryUK BiobankVeteran ProgramMendelian randomisationLociHeritabilitySNPsPhenotypeEast AsiansSimilar patternCardiometabolic phenotypesBi-ancestral depression GWAS in the Million Veteran Program and meta-analysis in >1.2 million individuals highlight new therapeutic directions
Levey DF, Stein MB, Wendt FR, Pathak GA, Zhou H, Aslan M, Quaden R, Harrington KM, Nuñez YZ, Overstreet C, Radhakrishnan K, Sanacora G, McIntosh AM, Shi J, Shringarpure SS, Concato J, Polimanti R, Gelernter J. Bi-ancestral depression GWAS in the Million Veteran Program and meta-analysis in >1.2 million individuals highlight new therapeutic directions. Nature Neuroscience 2021, 24: 954-963. PMID: 34045744, PMCID: PMC8404304, DOI: 10.1038/s41593-021-00860-2.Peer-Reviewed Original ResearchConceptsTranscriptome-wide association studyMillion Veteran ProgramTranscriptome-wide association study (TWAS) analysisGenomic risk lociComplex psychiatric traitsGenetic architectureRisk lociGene expressionAssociation studiesLikely pathogenicityPsychiatric traitsVeteran ProgramNew therapeutic directionEuropean ancestryNew insightsAncestryUK BiobankAfrican ancestrySubstantial replicationExpressionLarge independent cohortsGWASTherapeutic directionsGenesLociUnderstanding the comorbidity between posttraumatic stress severity and coronary artery disease using genome-wide information and electronic health records
Polimanti R, Wendt FR, Pathak GA, Tylee DS, Tcheandjieu C, Hilliard AT, Levey DF, Adhikari K, Gaziano JM, O’Donnell C, Assimes TL, Stein MB, Gelernter J. Understanding the comorbidity between posttraumatic stress severity and coronary artery disease using genome-wide information and electronic health records. Molecular Psychiatry 2022, 27: 3961-3969. PMID: 35986173, PMCID: PMC10986859, DOI: 10.1038/s41380-022-01735-z.Peer-Reviewed Original ResearchConceptsCoronary artery diseasePosttraumatic stress disorderElectronic health recordsMillion Veteran ProgramArtery diseaseTotal scoreCAD diagnosisPlatelet amyloid precursor proteinHealth recordsPosttraumatic stress severityAmyloid precursor proteinEarly CAD diagnosisUK BiobankBidirectional relationshipTwo-sample Mendelian randomization (MR) analysisMendelian randomization analysisCAD riskHigh morbidityPTSD symptom severityCARDIoGRAMplusC4D consortiumPleiotropic mechanismsSymptom severityLongitudinal changesDiscordant effectsStress disorder
2024
F96. ALCOHOL USE AND DEMENTIA IN DIVERSE POPULATIONS
Topiwala A, Levey D, Zhou H, Deak J, Adhikari K, Ebmeier K, Bell S, Burgess S, Nichols T, Gaziano M, Stein M, Gelernter J. F96. ALCOHOL USE AND DEMENTIA IN DIVERSE POPULATIONS. European Neuropsychopharmacology 2024, 87: 256-257. DOI: 10.1016/j.euroneuro.2024.08.507.Peer-Reviewed Original ResearchMillion Veteran ProgramDementia riskMendelian randomizationDementia casesAlcohol usePrevalence of alcohol use disordersImpact of alcohol useRandom-effects meta-analysisAlcohol use disorder prevalenceProspective cohort studyStandard deviation increaseObservational associationsUK BiobankVeteran ProgramLevels of drinkingPopulation prevalenceAlcohol consumptionAlcohol use disorderCohort studyDisorder prevalenceDementiaDependent drinkersDose-response relationshipGenetic associationLight drinkersPolygenic liability for anxiety in association with comorbid anxiety in multiple sclerosis
Kowalec K, Harder A, Dolovich C, Fitzgerald K, Salter A, Lu Y, Bernstein C, Bolton J, Cutter G, Fisk J, Gelernter J, Graff L, Hägg S, Hitchon C, Levey D, Lublin F, McKay K, Patten S, Patki A, Stein M, Tiwari H, Wolinsky J, Marrie R. Polygenic liability for anxiety in association with comorbid anxiety in multiple sclerosis. Annals Of Clinical And Translational Neurology 2024, 11: 1393-1404. PMID: 38715244, PMCID: PMC11187942, DOI: 10.1002/acn3.52025.Peer-Reviewed Original ResearchPolygenic scoresEuropean genetic ancestryUK BiobankAnxious symptomsIncreased oddsGenetic ancestrySelf-reported physician-diagnosedGenetic burdenComorbid anxietyGenome-wide association studiesCase-control designUnited States cohortDirection of effectAssociated with comorbid anxietyPhysician-diagnosedAssociated with disability progressionIndex diseaseStates cohortAnxiety symptomsMeta-analysesAssociation studiesSummary statisticsCurrent symptomsPolygenic liabilityRisk predictionWhole-exome sequencing in UK Biobank reveals rare genetic architecture for depression
Tian R, Ge T, Kweon H, Rocha D, Lam M, Liu J, Singh K, Levey D, Gelernter J, Stein M, Tsai E, Huang H, Chabris C, Lencz T, Runz H, Chen C. Whole-exome sequencing in UK Biobank reveals rare genetic architecture for depression. Nature Communications 2024, 15: 1755. PMID: 38409228, PMCID: PMC10897433, DOI: 10.1038/s41467-024-45774-2.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesRare coding variantsWhole-exome sequencingGenetic architectureGenetic relationshipsLoss-of-function intolerant genesContribution of rare coding variantsRare damagingAssociated with risk of depressionElectronic health recordsUK Biobank participantsPolygenic risk scoresRisk of depressionAssociated with riskIntolerant genesRisk lociAssociation studiesCoding variantsBiobank participantsHealth recordsUK BiobankDepression definitionsDepression riskBurden analysisRare variantsPleiotropy and genetically inferred causality linking multisite chronic pain to substance use disorders
Koller D, Friligkou E, Stiltner B, Pathak G, Løkhammer S, Levey D, Zhou H, Hatoum A, Deak J, Kember R, Treur J, Kranzler H, Johnson E, Stein M, Gelernter J, Polimanti R. Pleiotropy and genetically inferred causality linking multisite chronic pain to substance use disorders. Molecular Psychiatry 2024, 29: 2021-2030. PMID: 38355787, PMCID: PMC11324857, DOI: 10.1038/s41380-024-02446-3.Peer-Reviewed Original ResearchMultisite chronic painSubstance use disordersChronic painUK BiobankUse disorderMillion Veteran ProgramSNP-based heritabilityGenome-wide association statisticsMR analysisPotential causal relationshipVeteran ProgramPleiotropy analysisTobacco usePleiotropic variantsOpioid use disorderAssociation statisticsCannabis use disorderAlcohol use disorderMeta-analysesBrain-wide analysisImaging phenotypesBi-directional relationshipPainPleiotropyBiobank
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 samplePredisposition
2022
Sex-Specific Genetic and Transcriptomic Liability to Neuroticism
Wendt FR, Pathak GA, Singh K, Stein MB, Koenen KC, Krystal JH, Gelernter J, Davis LK, Polimanti R. Sex-Specific Genetic and Transcriptomic Liability to Neuroticism. Biological Psychiatry 2022, 93: 243-252. PMID: 36244801, PMCID: PMC10508260, DOI: 10.1016/j.biopsych.2022.07.019.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesTranscriptomic profilesAssociation studiesSingle nucleotide polymorphism heritabilityGene expression variationGenome-wide significanceSex-specific geneticChromosomal variationTranscriptomic changesRisk lociExpression variationBiological processesMolecular pathwaysLociPolygenic associationSex-specific effectsGenetic correlatesPolygenic scoresUK BiobankGenetic riskNCOA6GeneticsHeritabilityPathwayFemalesUsing phenotype risk scores to enhance gene discovery for generalized anxiety disorder and posttraumatic stress disorder
Wendt FR, Pathak GA, Deak JD, De Angelis F, Koller D, Cabrera-Mendoza B, Lebovitch DS, Levey DF, Stein MB, Kranzler HR, Koenen KC, Gelernter J, Huckins LM, Polimanti R. Using phenotype risk scores to enhance gene discovery for generalized anxiety disorder and posttraumatic stress disorder. Molecular Psychiatry 2022, 27: 2206-2215. PMID: 35181757, PMCID: PMC9133008, DOI: 10.1038/s41380-022-01469-y.Peer-Reviewed Original Research
2020
Expanding the genetic architecture of nicotine dependence and its shared genetics with multiple traits
Quach BC, Bray MJ, Gaddis NC, Liu M, Palviainen T, Minica CC, Zellers S, Sherva R, Aliev F, Nothnagel M, Young KA, Marks JA, Young H, Carnes MU, Guo Y, Waldrop A, Sey NYA, Landi MT, McNeil DW, Drichel D, Farrer LA, Markunas CA, Vink JM, Hottenga JJ, Iacono WG, Kranzler HR, Saccone NL, Neale MC, Madden P, Rietschel M, Marazita ML, McGue M, Won H, Winterer G, Grucza R, Dick DM, Gelernter J, Caporaso NE, Baker TB, Boomsma DI, Kaprio J, Hokanson JE, Vrieze S, Bierut LJ, Johnson EO, Hancock DB. Expanding the genetic architecture of nicotine dependence and its shared genetics with multiple traits. Nature Communications 2020, 11: 5562. PMID: 33144568, PMCID: PMC7642344, DOI: 10.1038/s41467-020-19265-z.Peer-Reviewed Original ResearchConceptsGenome-wide significant lociGenome-wide association studiesNearby gene expressionExpression of genesSmoking traitsGenetic architectureSignificant lociGenetic variationMultiple traitsGene expressionAssociation studiesLociTraitsGenetic knowledgeComposite phenotypeUK BiobankExpressionTENM2GNAI1GenesGeneticsVariantsPhenotypeLeveraging 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
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
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