2024
Using Medical Records to Investigate the Genetics of Treatment-Resistant Depression Across Health Care Systems
Polimanti R. Using Medical Records to Investigate the Genetics of Treatment-Resistant Depression Across Health Care Systems. American Journal Of Psychiatry 2024, 181: 569-571. PMID: 38946279, DOI: 10.1176/appi.ajp.20240377.Peer-Reviewed Original ResearchGenome-wide association analyses identify 95 risk loci and provide insights into the neurobiology of post-traumatic stress disorder
Nievergelt C, Maihofer A, Atkinson E, Chen C, Choi K, Coleman J, Daskalakis N, Duncan L, Polimanti R, Aaronson C, Amstadter A, Andersen S, Andreassen O, Arbisi P, Ashley-Koch A, Austin S, Avdibegoviç E, Babić D, Bacanu S, Baker D, Batzler A, Beckham J, Belangero S, Benjet C, Bergner C, Bierer L, Biernacka J, Bierut L, Bisson J, Boks M, Bolger E, Brandolino A, Breen G, Bressan R, Bryant R, Bustamante A, Bybjerg-Grauholm J, Bækvad-Hansen M, Børglum A, Børte S, Cahn L, Calabrese J, Caldas-de-Almeida J, Chatzinakos C, Cheema S, Clouston S, Colodro-Conde L, Coombes B, Cruz-Fuentes C, Dale A, Dalvie S, Davis L, Deckert J, Delahanty D, Dennis M, Desarnaud F, DiPietro C, Disner S, Docherty A, Domschke K, Dyb G, Kulenović A, Edenberg H, Evans A, Fabbri C, Fani N, Farrer L, Feder A, Feeny N, Flory J, Forbes D, Franz C, Galea S, Garrett M, Gelaye B, Gelernter J, Geuze E, Gillespie C, Goleva S, Gordon S, Goçi A, Grasser L, Guindalini C, Haas M, Hagenaars S, Hauser M, Heath A, Hemmings S, Hesselbrock V, Hickie I, Hogan K, Hougaard D, Huang H, Huckins L, Hveem K, Jakovljević M, Javanbakht A, Jenkins G, Johnson J, Jones I, Jovanovic T, Karstoft K, Kaufman M, Kennedy J, Kessler R, Khan A, Kimbrel N, King A, Koen N, Kotov R, Kranzler H, Krebs K, Kremen W, Kuan P, Lawford B, Lebois L, Lehto K, Levey D, Lewis C, Liberzon I, Linnstaedt S, Logue M, Lori A, Lu Y, Luft B, Lupton M, Luykx J, Makotkine I, Maples-Keller J, Marchese S, Marmar C, Martin N, Martínez-Levy G, McAloney K, McFarlane A, McLaughlin K, McLean S, Medland S, Mehta D, Meyers J, Michopoulos V, Mikita E, Milani L, Milberg W, Miller M, Morey R, Morris C, Mors O, Mortensen P, Mufford M, Nelson E, Nordentoft M, Norman S, Nugent N, O’Donnell M, Orcutt H, Pan P, Panizzon M, Pathak G, Peters E, Peterson A, Peverill M, Pietrzak R, Polusny M, Porjesz B, Powers A, Qin X, Ratanatharathorn A, Risbrough V, Roberts A, Rothbaum A, Rothbaum B, Roy-Byrne P, Ruggiero K, Rung A, Runz H, Rutten B, de Viteri S, Salum G, Sampson L, Sanchez S, Santoro M, Seah C, Seedat S, Seng J, Shabalin A, Sheerin C, Silove D, Smith A, Smoller J, Sponheim S, Stein D, Stensland S, Stevens J, Sumner J, Teicher M, Thompson W, Tiwari A, Trapido E, Uddin M, Ursano R, Valdimarsdóttir U, Van Hooff M, Vermetten E, Vinkers C, Voisey J, Wang Y, Wang Z, Waszczuk M, Weber H, Wendt F, Werge T, Williams M, Williamson D, Winsvold B, Winternitz S, Wolf C, Wolf E, Xia Y, Xiong Y, Yehuda R, Young K, Young R, Zai C, Zai G, Zervas M, Zhao H, Zoellner L, Zwart J, deRoon-Cassini T, van Rooij S, van den Heuvel L, Stein M, Ressler K, Koenen K. Genome-wide association analyses identify 95 risk loci and provide insights into the neurobiology of post-traumatic stress disorder. Nature Genetics 2024, 56: 792-808. PMID: 38637617, DOI: 10.1038/s41588-024-01707-9.Peer-Reviewed Original ResearchConceptsMeta-analysis of genome-wide association studiesGenome-wide significant lociMulti-ancestry meta-analysisGenome-wide association analysisGenome-wide association studiesIndividuals of European ancestryPotential causal genesNative American ancestryMulti-omics approachPost-traumatic stress disorderAdmixed individualsSignificant lociRisk lociCausal genesAssociation studiesAssociation analysisFunctional genesTranscription factorsGenetic studiesAmerican ancestryEuropean ancestryAxon guidanceSynaptic structureLociGenesEffects of genetically predicted posttraumatic stress disorder on autoimmune phenotypes
Maihofer A, Ratanatharathorn A, Hemmings S, Costenbader K, Michopoulos V, Polimanti R, Rothbaum A, Seedat S, Mikita E, Smith A, Salem R, Shaffer R, Wu T, Sebat J, Ressler K, Stein M, Koenen K, Wolf E, Sumner J, Nievergelt C. Effects of genetically predicted posttraumatic stress disorder on autoimmune phenotypes. Translational Psychiatry 2024, 14: 172. PMID: 38561342, PMCID: PMC10984931, DOI: 10.1038/s41398-024-02869-0.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderMendelian randomizationTwo-sample Mendelian randomizationLinkage disequilibrium score regressionGenome-wide significant single nucleotide polymorphismsCorrelated horizontal pleiotropyGenetic architectures of phenotypesMultivariable MR analysisSignificant single nucleotide polymorphismsAssociation of posttraumatic stress disorderCausal effectsSingle nucleotide polymorphismsGenetic correlationsMR-PRESSOHorizontal pleiotropyStress disorderMR analysisScore regressionGenetic architectureC-reactive proteinInverse varianceMR estimatesNucleotide polymorphismsPathway variablesEpidemiological evidenceClinical spectrum of Transthyretin amyloidogenic mutations among diverse population origins
De Lillo A, Pathak G, Low A, De Angelis F, Abou Alaiwi S, Miller E, Fuciarelli M, Polimanti R. Clinical spectrum of Transthyretin amyloidogenic mutations among diverse population origins. Human Genomics 2024, 18: 31. PMID: 38523305, PMCID: PMC10962184, DOI: 10.1186/s40246-024-00596-7.Peer-Reviewed Original ResearchConceptsCardiac congenital anomaliesAmyloidogenic mutationsCross-ancestry meta-analysisCongenital anomaliesComplex genotype-phenotype correlationsVal122Ile mutationGenotype-phenotype correlationPeripheral nerve disordersHereditary form of amyloidosisAncestry-specificCross-ancestryEuropean-descent individualsEast AsiansTTR-related amyloidosisIndividuals of African descentPopulation originClinical presentationAtrioventricular blockClinical spectrumDelayed diagnosisTTR mutationsAfrican descentNerve disordersTransthyretin mutationMutationsGenetic contribution to the comorbidity between attention-deficit/hyperactivity disorder and substance use disorders
Koller D, Mitjans M, Kouakou M, Friligkou E, Cabrera-Mendoza B, Deak J, Llonga N, Pathak G, Stiltner B, Løkhammer S, Levey D, Zhou H, Hatoum A, Kember R, Kranzler H, Stein M, Corominas R, Demontis D, Artigas M, Ramos-Quiroga J, Gelernter J, Ribasés M, Cormand B, Polimanti R. Genetic contribution to the comorbidity between attention-deficit/hyperactivity disorder and substance use disorders. Psychiatry Research 2024, 333: 115758. PMID: 38335780, PMCID: PMC11157987, DOI: 10.1016/j.psychres.2024.115758.Peer-Reviewed Original ResearchConceptsUse disorderGenome-wide association studiesGenomic structural equation modelingCannabis use disorderAlcohol Use Disorders Identification TestAttention-deficit/hyperactivity disorderAlcohol use disorderProblematic alcohol useSubstance use disordersTwo-sample Mendelian randomization analysisLinkage disequilibrium score regression analysisDisorders Identification TestMendelian randomization analysisAssociated with increased oddsOdds of ADHDOpioid use disorderAttention-deficit/hyperactivityGWAS meta-analysesAlcohol dependenceStructural equation modelingNicotine dependenceInvestigate genetic correlationsADHDPolygenic riskStrength of evidenceFunctional correlates of a novel 8-factor model of PTSD in U.S. military veterans: Results from the National Health and Resilience in Veterans Study
Stiltner B, Fischer I, Duek O, Polimanti R, Harpaz-Rotem I, Pietrzak R. Functional correlates of a novel 8-factor model of PTSD in U.S. military veterans: Results from the National Health and Resilience in Veterans Study. Journal Of Psychiatric Research 2024, 171: 69-74. PMID: 38244335, DOI: 10.1016/j.jpsychires.2024.01.017.Peer-Reviewed Original ResearchConceptsModels of posttraumatic stress disorderPosttraumatic stress disorderNational Health and ResilienceU.S. military veteransArousal symptomsSuicidal ideationVeterans StudyCurrent depressionSymptom clustersMilitary veteransPosttraumatic stress disorder symptom clustersPosttraumatic stress disorder symptomsPosttraumatic Stress Disorder ChecklistAnxious arousal symptomsDysphoric arousal symptomsIntrusive symptom clustersOdds of suicidal ideationFunctional correlatesMulti-faceted disorderExternalizing behavioral symptomsAssociated with lower oddsAssociated with higher oddsSymptom structureAvoidance symptomsDSM-5Genetic 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 smoking
2023
Evaluating a novel 8-factor dimensional model of PTSD in U.S. military veterans: Results from the National Health and Resilience in Veterans Study
Stiltner B, Fischer I, Duek O, Polimanti R, Harpaz-Rotem I, Pietrzak R. Evaluating a novel 8-factor dimensional model of PTSD in U.S. military veterans: Results from the National Health and Resilience in Veterans Study. Journal Of Affective Disorders 2023, 346: 303-307. PMID: 37979626, DOI: 10.1016/j.jad.2023.11.041.Peer-Reviewed Original ResearchConceptsIndex traumaPTSD symptomsNational HealthPosttraumatic stress disorder (PTSD) symptomsVeterans StudyMilitary veteransTrauma-exposed populationsClinician-administered interviewU.S. military veteransConfirmatory factor analysisDSM-5 modelStrong significant associationTrauma exposureIntrusive symptomsDisorder symptomsCombat exposureHigh riskU.S. veteransDSM-5Significant associationSymptomsInterpersonal violenceFactor analysisPTSDScarce researchCharacterizing the polygenic architecture of complex traits in populations of East Asian and European descent
De Lillo A, Wendt F, Pathak G, Polimanti R. Characterizing the polygenic architecture of complex traits in populations of East Asian and European descent. Human Genomics 2023, 17: 67. PMID: 37475089, PMCID: PMC10360343, DOI: 10.1186/s40246-023-00514-3.Peer-Reviewed Original ResearchModeling the longitudinal changes of ancestry diversity in the Million Veteran Program
Wendt F, Pathak G, Vahey J, Qin X, Koller D, Cabrera-Mendoza B, Haeny A, Harrington K, Rajeevan N, Duong L, Levey D, De Angelis F, De Lillo A, Bigdeli T, Pyarajan S, Gaziano J, Gelernter J, Aslan M, Provenzale D, Helmer D, Hauser E, Polimanti R. Modeling the longitudinal changes of ancestry diversity in the Million Veteran Program. Human Genomics 2023, 17: 46. PMID: 37268996, PMCID: PMC10239111, DOI: 10.1186/s40246-023-00487-3.Peer-Reviewed Original ResearchSex 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 outcomesEnrichment of self-domestication and neural crest function loci in the heritability of neurodevelopmental disorders
Koller D, Benítez-Burraco A, Polimanti R. Enrichment of self-domestication and neural crest function loci in the heritability of neurodevelopmental disorders. Human Genetics 2023, 142: 1271-1279. PMID: 36930228, PMCID: PMC10472204, DOI: 10.1007/s00439-023-02541-5.Peer-Reviewed Original ResearchEpidemiologic 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 study
2022
Denisovan and Neanderthal archaic introgression differentially impacted the genetics of complex traits in modern populations
Koller D, Wendt F, Pathak G, De Lillo A, De Angelis F, Cabrera-Mendoza B, Tucci S, Polimanti R. Denisovan and Neanderthal archaic introgression differentially impacted the genetics of complex traits in modern populations. BMC Biology 2022, 20: 249. PMID: 36344982, PMCID: PMC9641937, DOI: 10.1186/s12915-022-01449-2.Peer-Reviewed Original ResearchConceptsArchaic introgressionComplex traitsDenisovan introgressionNeanderthal allelesNeanderthal introgressionSignatures of admixtureAncestry groupsModern populationsPhenome-wide association studyModern human populationsMajor histocompatibility complex regionIntrogressionEvolutionary pressureGenetic poolDisease heritabilityGenomic signaturesEAS populationsExtinct NeanderthalsAssociation studiesMetabolic traitsDenisovansUK BiobankRed hair colorEuropean descentHuman traitsUnderstanding 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 disorderAn 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 studiesColitisAsthmaThe association of obesity-related traits on COVID-19 severity and hospitalization is affected by socio-economic status: a multivariable Mendelian randomization study
Cabrera-Mendoza B, Wendt FR, Pathak GA, De Angelis F, De Lillo A, Koller D, Polimanti R. The association of obesity-related traits on COVID-19 severity and hospitalization is affected by socio-economic status: a multivariable Mendelian randomization study. International Journal Of Epidemiology 2022, 51: 1371-1383. PMID: 35751636, PMCID: PMC9278255, DOI: 10.1093/ije/dyac129.Peer-Reviewed Original ResearchConceptsSevere respiratory COVID-19COVID-19 severityCOVID-19 outcomesSocio-economic statusMendelian randomization studyObesity-related traitsLower oddsCOVID-19Randomization studyCoronavirus disease 2019 (COVID-19) severityBody mass indexWaist-hip ratioCOVID-19 infectionTwo-sample MR approachAssociation of incomeMultivariable Mendelian randomization studyGenetically regulated multi-omics study for symptom clusters of posttraumatic stress disorder highlights pleiotropy with hematologic and cardio-metabolic traits
Pathak GA, Singh K, Wendt FR, Fleming TW, Overstreet C, Koller D, Tylee DS, De Angelis F, Cabrera Mendoza B, Levey DF, Koenen KC, Krystal JH, Pietrzak RH, O’ Donell C, Gaziano JM, Falcone G, Stein MB, Gelernter J, Pasaniuc B, Mancuso N, Davis LK, Polimanti R. Genetically regulated multi-omics study for symptom clusters of posttraumatic stress disorder highlights pleiotropy with hematologic and cardio-metabolic traits. Molecular Psychiatry 2022, 27: 1394-1404. PMID: 35241783, PMCID: PMC9210390, DOI: 10.1038/s41380-022-01488-9.Peer-Reviewed Original ResearchConceptsLocal genetic correlationsCell type-specific expressionVanderbilt University biorepositoryMulti-omics studiesMulti-omics investigationsDorsolateral prefrontal cortex tissueGenomic evidenceLaboratory traitsSpecific expressionCardio-metabolic traitsMillion Veteran ProgramPrefrontal cortex tissueMiR-148GenesGenetic correlationsRegulatory profileTraitsProtein expressionCardiometabolic traitsExpressionVeteran ProgramCortex tissueBiological heterogeneitySplicingPrioritization approachUsing 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
The integration of genetically-regulated transcriptomics and electronic health records highlights a pattern of medical outcomes related to increased hepatic transthyretin expression
Pathak GA, De Lillo A, Wendt FR, De Angelis F, Koller D, Mendoza B, Jacoby D, Miller EJ, Buxbaum JN, Polimanti R. The integration of genetically-regulated transcriptomics and electronic health records highlights a pattern of medical outcomes related to increased hepatic transthyretin expression. Amyloid 2021, 29: 110-119. PMID: 34935565, PMCID: PMC9213571, DOI: 10.1080/13506129.2021.2018678.Peer-Reviewed Original ResearchConceptsGenotype-Tissue Expression (GTEx) projectMulti-tissue analysisElectronic health recordsTTR amyloid formationGenetic regulationExpression projectRNA interferenceTranscriptomic profilesGene expressionExpression informationHepatic expressionHealth outcomesPhenotypic informationAmyloid formationHealth recordsCarpal tunnel syndromeTranscriptionTransthyretin expressionSystemic amyloidosesHepatic transcriptionPathological processesExpressionTunnel syndromeGastrointestinal diseasesSurgical procedures