Featured Publications
Genetic Liability to Posttraumatic Stress Disorder Symptoms and Its Association With Cardiometabolic and Respiratory Outcomes
Pathak G, Singh K, Choi K, Fang Y, Kouakou M, Lee Y, Zhou X, Fritsche L, Wendt F, Davis L, Polimanti R. Genetic Liability to Posttraumatic Stress Disorder Symptoms and Its Association With Cardiometabolic and Respiratory Outcomes. JAMA Psychiatry 2024, 81: 34-44. PMID: 37910111, PMCID: PMC10620678, DOI: 10.1001/jamapsychiatry.2023.4127.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderBody mass indexMass General BrighamPTSD symptom severityElectronic health recordsSymptom severityRespiratory outcomesMass indexRisk factorsMedical outcomesHealth outcomesMendelian randomizationDisease categoriesGenetic liabilityMeta-analyzed associationsSignificant medical outcomesNonspecific chest painC-reactive proteinMental health disordersUK BiobankMultivariable Mendelian randomizationPosttraumatic stress disorder (PTSD) symptomsChest painCardiac dysrhythmiasTobacco smokingEpidemiologic and Genetic Associations of Endometriosis With Depression, Anxiety, and Eating Disorders
Koller D, Pathak G, Wendt F, Tylee D, Levey D, Overstreet C, Gelernter J, Taylor H, Polimanti R. Epidemiologic and Genetic Associations of Endometriosis With Depression, Anxiety, and Eating Disorders. JAMA Network Open 2023, 6: e2251214. PMID: 36652249, PMCID: PMC9856929, DOI: 10.1001/jamanetworkopen.2022.51214.Peer-Reviewed Original ResearchConceptsPsychiatric comorbidityMAIN OUTCOMEMental healthIrritable bowel syndromeBody mass indexAssociation of endometriosisOdds of depressionSevere physical symptomsPain-related phenotypesWomen's mental healthMultivariate regression analysisOdds of endometriosisBowel syndromeGenetic associationMass indexGynecologic pathologyMillion Veteran ProgramEndometriosisPsychiatric disordersWomen's healthFemale controlsPleiotropic mechanismsPhysical symptomsComorbiditiesFinnGen studySex-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 riskNCOA6GeneticsHeritabilityPathwayFemalesPhenome-Wide Association Study for Alcohol and Nicotine Risk Alleles in 26394 Women
Polimanti R, Kranzler HR, Gelernter J. Phenome-Wide Association Study for Alcohol and Nicotine Risk Alleles in 26394 Women. Neuropsychopharmacology 2016, 41: 2688-2696. PMID: 27187070, PMCID: PMC5026736, DOI: 10.1038/npp.2016.72.Peer-Reviewed Original ResearchConceptsHealth initiativesRisk allelesSocioeconomic statusPhenome-wide association studyWomen's Health InitiativeMetabolism-related mechanismsMedication useLung cancerTobacco useDietary habitsSmoking behaviorNicotine useReproductive historyReproductive healthSuggestive findingsAlcohol useAnthropometric characteristicsMental healthHealth conditionsMetabolic conditionsCausative relationshipAssociation studiesDrinking behaviorADH1BAssociation
2024
Association of deployment characteristics and exposures with persistent ill health among 1990-1991 Gulf War veterans in the VA Million Veteran Program
Steele L, Quaden R, Ahmed S, Harrington K, Duong L, Ko J, Gifford E, Polimanti R, Gaziano J, Aslan M, Helmer D, Hauser E. Association of deployment characteristics and exposures with persistent ill health among 1990-1991 Gulf War veterans in the VA Million Veteran Program. Environmental Health 2024, 23: 92. PMID: 39456027, PMCID: PMC11520114, DOI: 10.1186/s12940-024-01118-7.Peer-Reviewed Original ResearchConceptsMillion Veteran ProgramVA Million Veteran ProgramGulf War veteransIll healthHealth outcomesGulf War IllnessVeteran ProgramMilitary characteristicsWar veteransChronic ill healthCenters for Disease Control and Prevention criteriaGulf War serviceEvaluation of genetic factorsGulf War exposureVeterans' healthPopulation of U.S.Pyridostigmine bromide pillsHealthcare providersWartime exposuresGulf War deploymentResultsThe final cohortVeteran cohortDeployment exposuresHealth problemsVeteransAssociation patterns of antisocial personality disorder across substance use disorders
Low A, Stiltner B, Nunez Y, Adhikari K, Deak J, Pietrzak R, Kranzler H, Gelernter J, Polimanti R. Association patterns of antisocial personality disorder across substance use disorders. Translational Psychiatry 2024, 14: 346. PMID: 39198385, PMCID: PMC11358160, DOI: 10.1038/s41398-024-03054-z.Peer-Reviewed Original ResearchConceptsAntisocial personality disorderSubstance use disordersPersonality disorderUse disorderAssociation of antisocial personality disorderPresence of antisocial personality disorderPrevalence of antisocial personality disorderHazardous useDSM-5 SUD diagnosesSubstance use disorder severityDiagnostic criteriaInteraction effects with sexTobacco use disorderDSM-5Association of alcoholSUD diagnosisDisordersCocaineRacial/ethnic backgroundsIndividualsCocUDSeverityCannabisAssociation patternsAssociation
2023
Sex differences in the polygenic architecture of hearing problems in adults
De Angelis F, Zeleznik O, Wendt F, Pathak G, Tylee D, De Lillo A, Koller D, Cabrera-Mendoza B, Clifford R, Maihofer A, Nievergelt C, Curhan G, Curhan S, Polimanti R. Sex differences in the polygenic architecture of hearing problems in adults. Genome Medicine 2023, 15: 36. PMID: 37165447, PMCID: PMC10173489, DOI: 10.1186/s13073-023-01186-3.Peer-Reviewed Original ResearchConceptsPolygenic architectureRisk lociGenome-wide investigationLarge-scale genetic studiesTranscriptomic regulationGWAS findingsTranscriptomic associationsGene interactionsPotential roleRegulation analysisGenetic studiesInference analysisMillion Veteran ProgramHealth Professionals FollowMolecular pathwaysPolygenic riskPreventive screening programsMultivariate interaction analysisNovel insightsCentral nervous systemEnvironmental risk factorsSex-stratified analysesSex-specific analysesSex differencesMental health outcomes
2022
Genetic liability to suicidal thoughts and behaviors and risk of suicide attempt in US military veterans: moderating effects of cumulative trauma burden
Nichter B, Koller D, De Angelis F, Wang J, Girgenti M, Na P, Hill M, Norman S, Krystal J, Gelernter J, Polimanti R, Pietrzak R. Genetic liability to suicidal thoughts and behaviors and risk of suicide attempt in US military veterans: moderating effects of cumulative trauma burden. Psychological Medicine 2022, 53: 6325-6333. PMID: 36444557, DOI: 10.1017/s0033291722003646.Peer-Reviewed Original ResearchConceptsPolygenic risk scoresUS military veteransLifetime suicide attemptsSuicide attemptsTrauma exposureTrauma burdenGenetic liabilityMilitary veteransDrug repurposing analysisPopulation-based sampleCumulative trauma exposureLifetime trauma exposureLow trauma exposureSuicide prediction modelsChronic inflammationInflammatory processNervous system developmentRisk scorePsychiatric characteristicsSuicidal behaviorExposure interactionsLarge genome-wide association studiesHigh levelsVeteransSuicidalityAPOL1 Risk Variants, Acute Kidney Injury, and Death in Participants With African Ancestry Hospitalized With COVID-19 From the Million Veteran Program
Hung AM, Shah SC, Bick AG, Yu Z, Chen HC, Hunt CM, Wendt F, Wilson O, Greevy RA, Chung CP, Suzuki A, Ho YL, Akwo E, Polimanti R, Zhou J, Reaven P, Tsao PS, Gaziano JM, Huffman JE, Joseph J, Luoh SW, Iyengar S, Chang KM, Casas JP, Matheny ME, O’Donnell C, Cho K, Tao R, Susztak K, Robinson-Cohen C, Tuteja S, Siew ED, Hung A, Wallbom A, Palacio A, Robey B, Jhala D, Fujii D, Cohen D, Boyko E, Jacono F, Villareal G, Garcon H, Gaziano J, Lichy J, Norton J, Beckham J, Whittle J, Huffman J, Moser J, Greco J, Walsh J, Harley J, Wells J, Klein J, Moorman J, Constans J, Fayad J, Casas J, Xu J, Liao K, Alexander K, Cho K, Hammer K, Oursler K, Mattocks K, Chang K, Dellitalia L, Hamner M, Whooley M, Murdoch M, Gaddy M, Godschalk M, Rauchman M, Huq M, Tandon N, Kosik N, Ratcliffe N, Okusaga O, Roussos P, Strollo P, Meyer P, Sriram P, Wilson P, Liang P, Tsao P, Balasubramanian P, Ramoni R, McArdle R, Hauger R, Servatius R, Smith R, Striker R, Mathew R, Gappy S, Pyarajan S, Gutierrez S, Gupta S, Aguayo S, Sharma S, Damrauer S, Kinlay S, Yeh S, Luoh S, Tuteja S, Mastorides S, Iyengar S, Bhushan S, Muralidhar S, Ahuja S, Liangpunsakul S, Assimes T, Morgan T, Stapley T, Sun Y, Ballas Z. APOL1 Risk Variants, Acute Kidney Injury, and Death in Participants With African Ancestry Hospitalized With COVID-19 From the Million Veteran Program. JAMA Internal Medicine 2022, 182: 386-395. PMID: 35089317, PMCID: PMC8980930, DOI: 10.1001/jamainternmed.2021.8538.Peer-Reviewed Original ResearchConceptsAcute kidney injuryNormal kidney functionHigh-risk groupAPOL1 risk variantsKidney functionAKI severityKidney injuryCohort studyMillion Veteran ProgramHigher oddsCOVID-19-associated acute kidney injuryRisk variantsMultivariable logistic regression analysisCOVID-19AKI risk factorsAKI severity stageRetrospective cohort studyAfrican ancestryApolipoprotein L1COVID-19 infectionCoronavirus disease 2019Logistic regression analysisHigh mortality rateVeteran ProgramAPOL1 kidney risk variantsUsing 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
2021
Potential causal effect of posttraumatic stress disorder on alcohol use disorder and alcohol consumption in individuals of European descent: A Mendelian Randomization Study
Bountress KE, Wendt F, Bustamante D, Agrawal A, Webb B, Gillespie N, Edenberg H, Sheerin C, Johnson E, Group T, Polimanti R, Amstadter A. Potential causal effect of posttraumatic stress disorder on alcohol use disorder and alcohol consumption in individuals of European descent: A Mendelian Randomization Study. Alcohol Clinical And Experimental Research 2021, 45: 1616-1623. PMID: 34120358, PMCID: PMC8429238, DOI: 10.1111/acer.14649.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderAlcohol use disorderStress disorderTrauma-related symptomsSelf-medication modelUse disordersAlcohol consumptionLarge-scale genome-wide association study (GWAS) dataCausal effectNicotine usePotential causal effectsPTSD coLatent analysisEtiologic influencesAlcohol phenotypesHealth behaviorsPrevention effortsCorrelated riskDisordersPsychiatric Genomics ConsortiumMendelian randomization studyFindingsIndividualsClinical studiesMillion Veteran ProgramBi-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 directionsGenesLociBiobank Scale Pharmacogenomics Informs the Genetic Underpinnings of Simvastatin Use
Wendt FR, Koller D, Pathak GA, Jacoby D, Miller EJ, Polimanti R. Biobank Scale Pharmacogenomics Informs the Genetic Underpinnings of Simvastatin Use. Clinical Pharmacology & Therapeutics 2021, 110: 777-785. PMID: 33837531, PMCID: PMC8376807, DOI: 10.1002/cpt.2260.Peer-Reviewed Original ResearchConceptsLDL-C concentrationsSimvastatin useLow-density lipoprotein cholesterol concentrationsLipoprotein cholesterol concentrationsDrug-metabolizing enzymesElectronic medical recordsStatin therapyStatin treatmentActivity scoreMedical recordsPilot cohortCholesterol concentrationsEuropean ancestry participantsMetabolizer phenotypeClinical decisionNAT2 allelesPolygenic riskNAT2Good responseUK BiobankBiological mechanismsPharmacogenesAssociationPotential benefitsPhenotype
2020
Epigenetic profiling of Italian patients identified methylation sites associated with hereditary transthyretin amyloidosis
De Lillo A, Pathak GA, De Angelis F, Di Girolamo M, Luigetti M, Sabatelli M, Perfetto F, Frusconi S, Manfellotto D, Fuciarelli M, Polimanti R. Epigenetic profiling of Italian patients identified methylation sites associated with hereditary transthyretin amyloidosis. Clinical Epigenetics 2020, 12: 176. PMID: 33203445, PMCID: PMC7672937, DOI: 10.1186/s13148-020-00967-6.Peer-Reviewed Original ResearchConceptsEpigenome-wide association studiesMethylation sitesEpigenetic differencesSignificant epigenetic differencesProtein interaction networksSignificant methylation changesAmyloidogenic mutationsDisease-causing mutationsProtein interactorsEpigenetic regulationHigh phenotypic variabilityEpigenetic profilingMethylation changesInteraction networksGene regionBiological processesMolecular mechanismsAssociation studiesMolecular pathwaysCoding mutationsPhenotypic variabilityNovel insightsGenesFiber formationMutationsAssociation 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 RevisionPolygenic 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 ResearchGenome-wide meta-analysis of problematic alcohol use in 435,563 individuals yields insights into biology and relationships with other traits
Zhou H, Sealock JM, Sanchez-Roige S, Clarke TK, Levey DF, Cheng Z, Li B, Polimanti R, Kember RL, Smith RV, Thygesen JH, Morgan MY, Atkinson SR, Thursz MR, Nyegaard M, Mattheisen M, Børglum AD, Johnson EC, Justice AC, Palmer AA, McQuillin A, Davis LK, Edenberg HJ, Agrawal A, Kranzler HR, Gelernter J. Genome-wide meta-analysis of problematic alcohol use in 435,563 individuals yields insights into biology and relationships with other traits. Nature Neuroscience 2020, 23: 809-818. PMID: 32451486, PMCID: PMC7485556, DOI: 10.1038/s41593-020-0643-5.Peer-Reviewed Original ResearchConceptsRegulatory genomic regionsGenome-wide association studiesNovel risk lociEuropean ancestry individualsPolygenic risk score analysisIndependent risk variantsGenetic architectureGenomic regionsRisk lociAssociation studiesGenetic relationshipsRisk genesGenetic correlationsPsychiatric traitsRisk variantsRisk score analysisTraitsGenetic heritabilityYields insightsBiobank samplesMendelian randomizationGenesLociBiologyHeritabilityLeveraging 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 ResearchReproducible Genetic Risk Loci for Anxiety: Results From ∼200,000 Participants in the Million Veteran Program
Levey DF, Gelernter J, Polimanti R, Zhou H, Cheng Z, Aslan M, Quaden R, Concato J, Radhakrishnan K, Bryois J, Sullivan PF, Stein M. Reproducible Genetic Risk Loci for Anxiety: Results From ∼200,000 Participants in the Million Veteran Program. American Journal Of Psychiatry 2020, 177: 223-232. PMID: 31906708, PMCID: PMC7869502, DOI: 10.1176/appi.ajp.2019.19030256.Peer-Reviewed Original ResearchConceptsNovel genome-wide significant associationsGene expressionGenome-wide significant signalsGenome-wide significant associationMillion Veteran ProgramWide association studyGenetic risk lociSignificant genetic correlationsGenetic risk mechanismsGenetic architectureGlobal regulatorChromosome 3Risk lociChromosome 6Chromosome 7Association studiesLargest GWASLarge biobanksGlobal regulationGenetic correlationsContinuous traitsVeteran ProgramGWASsLociPrevious GWASs
2019
Phenome-wide association study of TTR and RBP4 genes in 361,194 individuals reveals novel insights in the genetics of hereditary and wildtype transthyretin amyloidoses
De Lillo A, De Angelis F, Di Girolamo M, Luigetti M, Frusconi S, Manfellotto D, Fuciarelli M, Polimanti R. Phenome-wide association study of TTR and RBP4 genes in 361,194 individuals reveals novel insights in the genetics of hereditary and wildtype transthyretin amyloidoses. Human Genetics 2019, 138: 1331-1340. PMID: 31659433, DOI: 10.1007/s00439-019-02078-6.Peer-Reviewed Original ResearchConceptsNon-coding variantsPhenome-wide association studyAssociation studiesNovel insightsPhenotypic traitsMolecular basisPossible modifier genesRBP4 geneModifier genesRelevant phenotypesTTR locusGenesTTR functionTransthyretin amyloidosesMultiple testing correctionGene variationRBP4 variantsGeneticsPhenotypeTransthyretin geneTTR geneConvergent associationsHereditary formsClinical phenotypeVariants