2024
47. GENE DISCOVERY AND BIOLOGICAL INSIGHTS INTO ANXIETY DISORDERS FROM A MULTI-ANCESTRY GENOME-WIDE ASSOCIATION STUDY OF > 1.2 MILLION PARTICIPANTS
Friligkou E, Løkhammer S, Mendoza B, Shen J, He J, Deiana G, Zanoaga M, Asgel Z, Pilcher A, Di Lascio L, Makharashvili A, Koller D, Tylee D, Pathak G, Polimanti R. 47. GENE DISCOVERY AND BIOLOGICAL INSIGHTS INTO ANXIETY DISORDERS FROM A MULTI-ANCESTRY GENOME-WIDE ASSOCIATION STUDY OF > 1.2 MILLION PARTICIPANTS. European Neuropsychopharmacology 2024, 87: 74-75. DOI: 10.1016/j.euroneuro.2024.08.161.Peer-Reviewed Original ResearchMillion Veteran ProgramPolygenic riskLatent causal variable methodMulti-tissue transcriptome-wide association studyUK Biobank (UKBGenetic correlationsTranscriptome-wide association studyAnxiety disordersGenomic structural equation modelingLD score regressionLocal genetic correlationGWAS meta-analysisProteome-wide analysisGenetics of anxietyAssociated with anxietyMulti-omics informationS-MultiXcanVeteran ProgramLD scoresAncestry-specificTranscriptome-wideAncestral populationsCross-ancestryGene discoveryAssociation studiesGene discovery and biological insights into anxiety disorders from a large-scale multi-ancestry genome-wide association study
Friligkou E, Løkhammer S, Cabrera-Mendoza B, Shen J, He J, Deiana G, Zanoaga M, Asgel Z, Pilcher A, Di Lascio L, Makharashvili A, Koller D, Tylee D, Pathak G, Polimanti R. Gene discovery and biological insights into anxiety disorders from a large-scale multi-ancestry genome-wide association study. Nature Genetics 2024, 56: 2036-2045. PMID: 39294497, DOI: 10.1038/s41588-024-01908-2.Peer-Reviewed Original ResearchGenome-wide association studiesAnxiety disordersAssociation studiesMulti-ancestry genome-wide association studyPathogenesis of anxiety disordersHeritability of anxietyLocal genetic correlationProteome-wide analysisIndividuals of European descentAssociated with anxietyMulti-omics informationWidespread pleiotropyTranscriptome-widePolygenic risk scoresBipolar disorderAncestry-specificGene discoveryContinental groupsLimbic systemEast Asian groupsBiological insightsAnxietyEntorhinal cortexPhysical health domainBrain-specificBlood pressure changes during ketamine infusion for the treatment of depression
Ansari M, Pittman B, Tylee D, Ostroff R, Wilkinson S, Nikayin S. Blood pressure changes during ketamine infusion for the treatment of depression. General Hospital Psychiatry 2024, 90: 62-67. PMID: 38991311, DOI: 10.1016/j.genhosppsych.2024.07.001.Peer-Reviewed Original ResearchKetamine infusionBlood pressure changesBlood pressureRetrospective chart review of patientsChart review of patientsMedical history of hypertensionRetrospective chart reviewHistory of hypertensionSignificant blood pressureDiastolic blood pressureTreatment of depressionSevere hypertensionPatient demographicsHypertensive patientsInfusion sessionsMedical historyHypertensive eventsInfusionPatientsKetamineBP surgeCardiovascular monitoringBloodHypertensionPressure changes
2023
A perspective on translating genomic discoveries into targets for brain‐machine interface and deep brain stimulation devices
Valentim W, Tylee D, Polimanti R. A perspective on translating genomic discoveries into targets for brain‐machine interface and deep brain stimulation devices. WIREs Mechanisms Of Disease 2023, 16: e1635. PMID: 38059513, PMCID: PMC11163995, DOI: 10.1002/wsbm.1635.Peer-Reviewed Original ResearchPolysubstance addiction patterns among 7,989 individuals with cocaine use disorder
Stiltner B, Pietrzak R, Tylee D, Nunez Y, Adhikari K, Kranzler H, Gelernter J, Polimanti R. Polysubstance addiction patterns among 7,989 individuals with cocaine use disorder. IScience 2023, 26: 107336. PMID: 37554454, PMCID: PMC10405253, DOI: 10.1016/j.isci.2023.107336.Peer-Reviewed Original ResearchCocaine use disorderUse disordersAddiction patternsMixed bipolar episodesLatent class analysisDSM-5 diagnosisPosttraumatic stress disorderAntisocial personality disorderPsA severityMedication useHigher PSAPSA subgroupsHigher oddsBipolar episodesStress disorderPersonality disorderDisordersSubgroupsAgeSexClass analysisParticipantsComorbiditiesDiseaseDiagnosisSex 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 outcomesEpidemiologic 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. Obstetrical & Gynecological Survey 2023, 78: 282-283. DOI: 10.1097/01.ogx.0000935848.53207.07.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
T127. AUTOMATED PHENOTYPING OF DEPRESSIVE DISORDERS AND SYMPTOMS APPLIED TO THE ELECTRONIC MEDICAL RECORD OF THE YALE NEW HAVEN HEALTH SYSTEM
Tylee D, Hänsel K, Polimanti R, Schulz W. T127. AUTOMATED PHENOTYPING OF DEPRESSIVE DISORDERS AND SYMPTOMS APPLIED TO THE ELECTRONIC MEDICAL RECORD OF THE YALE NEW HAVEN HEALTH SYSTEM. European Neuropsychopharmacology 2022, 63: e237. DOI: 10.1016/j.euroneuro.2022.07.423.Peer-Reviewed Original ResearchUnderstanding 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 studiesColitisAsthmaUnderstanding the complex genetic architecture connecting rheumatoid arthritis, osteoporosis and inflammation: discovering causal pathways
Kasher M, Williams F, Freidin M, Malkin I, Cherny S, Benjamin E, Chasman D, Dehghan A, Ahluwalia T, Meigs J, Tracy R, Alizadeh B, Ligthart S, Bis J, Eiriksdottir G, Pankratz N, Gross M, Rainer A, Snieder H, Wilson J, Psaty B, Dupuis J, Prins B, Vaso U, Stathopoulou M, Franke L, Lehtimaki T, Koenig W, Jamshidi Y, Siest S, Abbasi A, Uitterlinden A, Abdollahi M, Schnabel R, Schick U, Nolte I, Kraja A, Hsu Y, Tylee D, Zwicker A, Uher R, Davey-Smith G, Morrison A, Hicks A, van Duijn C, Ward-Caviness C, Boerwinkle E, Rotter J, Rice K, Lange L, Perola M, de Geus E, Morris A, Makela K, Stacey D, Eriksson J, Frayling T, Slagboom E, Livshits G. Understanding the complex genetic architecture connecting rheumatoid arthritis, osteoporosis and inflammation: discovering causal pathways. Human Molecular Genetics 2022, 31: 2623-2632. PMID: 35349660, PMCID: PMC9402243, DOI: 10.1093/hmg/ddac061.Peer-Reviewed Original ResearchConceptsCausal single nucleotide polymorphismsSingle nucleotide polymorphismsGenetic architectureColocalization analysisSame molecular functionAnalysis of pleiotropyComplex genetic architectureGenome-wide association study summary statisticsOp phenotypeMolecular functionsGenomic regionsPleiotropyOsteoporosis ConsortiumGenetic relationshipsGenetic backgroundGenetic variantsNucleotide polymorphismsMendelian randomizationGenesTraitsPhenotypeGenetic factorsProtein bindingUK BiobankHorizontal pleiotropyGenetically 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 approach
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 smokingRole of microbes in the pathogenesis of neuropsychiatric disorders
Goswami A, Wendt FR, Pathak GA, Tylee DS, De Angelis F, De Lillo A, Polimanti R. Role of microbes in the pathogenesis of neuropsychiatric disorders. Frontiers In Neuroendocrinology 2021, 62: 100917. PMID: 33957173, PMCID: PMC8364482, DOI: 10.1016/j.yfrne.2021.100917.Peer-Reviewed Original ResearchConceptsNeuropsychiatric disordersDifferent anatomical sitesOral cavityAnatomical sitesHuman studiesBody sitesTranslational potentialPotential involvementPathogenesisGutMicrobial metabolitesDisordersBidirectional communicationStrong evidenceDiseaseNeurotransmittersBrainMicrobiome researchMicrobiome variationSex-stratified gene-by-environment genome-wide interaction study of trauma, posttraumatic-stress, and suicidality
Wendt FR, Pathak GA, Levey DF, Nuñez YZ, Overstreet C, Tyrrell C, Adhikari K, De Angelis F, Tylee DS, Goswami A, Krystal JH, Abdallah CG, Stein MB, Kranzler HR, Gelernter J, Polimanti R. Sex-stratified gene-by-environment genome-wide interaction study of trauma, posttraumatic-stress, and suicidality. Neurobiology Of Stress 2021, 14: 100309. PMID: 33665242, PMCID: PMC7905234, DOI: 10.1016/j.ynstr.2021.100309.Peer-Reviewed Original ResearchGenome-wide interaction studyRisk lociChromatin interaction profilesExtracellular matrix biologyGene-based analysisMatrix biologyMolecular basisTranscriptomic profilesInteraction studiesMultivariate geneGenetic perspectiveSNP effectsSuicidal behavior severityLociNovel targetGenesInteraction profilesSynaptic plasticityCellsInteractorsGenetic riskBiologyStressGxEIndependent cohort
2020
Characterizing the effect of background selection on the polygenicity of brain-related traits
Wendt FR, Pathak GA, Overstreet C, Tylee DS, Gelernter J, Atkinson EG, Polimanti R. Characterizing the effect of background selection on the polygenicity of brain-related traits. Genomics 2020, 113: 111-119. PMID: 33278486, PMCID: PMC7855394, DOI: 10.1016/j.ygeno.2020.11.032.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesBrain-related traitsGWAS of schizophreniaTrait-associated lociLocus effect sizesSubset of traitsGenotype networksGenetic architectureIntolerant regionsBrain-related phenotypesBackground selectionNatural selectionEvolutionary pressurePositive selectionSNP heritabilityLocal ancestryAssociation studiesTraitsFunctional significanceLociPolygenicityBinary annotationPhenotypeRisk allelesSize varianceInterleukin-6 Signaling Effects on Ischemic Stroke and Other Cardiovascular Outcomes
Georgakis M, Malik R, Gill D, Franceschini N, Sudlow C, Dichgans M, Lindstrom S, Wang L, Smith E, Gordon W, van Hylckama Vlieg A, de Andrade M, Brody J, Pattee J, Haessler J, Brumpton B, Chasman D, Suchon P, Chen M, Turman C, Germain M, Wiggins K, MacDonald J, Braekkan S, Armasu S, Pankratz N, Jackson R, Nielsen J, Giulianini F, Puurunen M, Ibrahim M, Heckbert S, Damrauer S, Natarajan P, Klarin D, de Vries P, SabaterLleal M, Huffman J, Bammler T, Frazer K, McCauley B, Taylor K, Pankow J, Reiner A, Gabrielsen M, Deleuze J, O’Donnell C, Kim J, McKnight B, Kraft P, Hansen J, Rosendaal F, Heit J, Psaty B, Tang W, Kooperberg C, Hveem K, Ridker P, Morange P, Johnson A, Kabrhel C, Trégouët D, Smith N, Benjamin E, Chasman D, Dehghan A, Ahluwalia T, Meigs J, Tracy R, Alizadeh B, Ligthart S, Bis J, Eiriksdottir G, Pankratz N, Gross M, Rainer A, Snieder H, Wilson J, Psaty B, Dupuis J, Prins B, Vaso U, Stathopoulou M, Franke L, Lehtimaki T, Koenig W, Jamshidi Y, Siest S, Abbasi A, Uitterlinden A, Abdollahi M, Schnabel R, Schick U, Nolte I, Kraja A, Hsu Y, Tylee D, Zwicker A, Uher R, Davey-Smith G, Morrison A, Hicks A, van Duijn C, Ward-Caviness C, Boerwinkle E, Rotter J, Rice K, Lange L, Perola M, de Geus E, Morris A, Makela K, Stacey D, Eriksson J, Frayling T, Slagboom E. Interleukin-6 Signaling Effects on Ischemic Stroke and Other Cardiovascular Outcomes. Circulation Genomic And Precision Medicine 2020, 13: e002872-e002872. PMID: 32397738, PMCID: PMC7299212, DOI: 10.1161/circgen.119.002872.Peer-Reviewed Original ResearchHeterogeneity and Polygenicity in Psychiatric Disorders: A Genome-Wide Perspective
Wendt FR, Pathak GA, Tylee DS, Goswami A, Polimanti R. Heterogeneity and Polygenicity in Psychiatric Disorders: A Genome-Wide Perspective. Chronic Stress 2020, 4: 2470547020924844. PMID: 32518889, PMCID: PMC7254587, DOI: 10.1177/2470547020924844.Peer-Reviewed Original Research
2019
M14 DISCRIMINATION OF MAJOR NEUROPSYCHIATRIC DISORDERS USING BLOOD-BASED TRANSCRIPTOMIC SIGNATURES
Hess J, Tylee D, Liu C, de Jong S, Ophoff R, Gardiner E, Sibille E, Turecki G, Tseng G, Tsuang M, Faraone S, Glatt S. M14 DISCRIMINATION OF MAJOR NEUROPSYCHIATRIC DISORDERS USING BLOOD-BASED TRANSCRIPTOMIC SIGNATURES. European Neuropsychopharmacology 2019, 29: s173. DOI: 10.1016/j.euroneuro.2019.08.114.Peer-Reviewed Original Research