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
2020
Interleukin-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 Research
2018
Genome Analyses of >200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways that Link Inflammation and Complex Disorders
Ligthart S, Vaez A, Võsa U, Stathopoulou M, de Vries P, Prins B, Van der Most P, Tanaka T, Naderi E, Rose L, Wu Y, Karlsson R, Barbalic M, Lin H, Pool R, Zhu G, Macé A, Sidore C, Trompet S, Mangino M, Sabater-Lleal M, Kemp J, Abbasi A, Kacprowski T, Verweij N, Smith A, Huang T, Marzi C, Feitosa M, Lohman K, Kleber M, Milaneschi Y, Mueller C, Huq M, Vlachopoulou E, Lyytikäinen L, Oldmeadow C, Deelen J, Perola M, Zhao J, Feenstra B, Amini M, Lahti J, Schraut K, Fornage M, Suktitipat B, Chen W, Li X, Nutile T, Malerba G, Luan J, Bak T, Schork N, Del Greco M. F, Thiering E, Mahajan A, Marioni R, Mihailov E, Eriksson J, Ozel A, Zhang W, Nethander M, Cheng Y, Aslibekyan S, Ang W, Gandin I, Yengo L, Portas L, Kooperberg C, Hofer E, Rajan K, Schurmann C, Hollander W, Ahluwalia T, Zhao J, Draisma H, Ford I, Timpson N, Teumer A, Huang H, Wahl S, Liu Y, Huang J, Uh H, Geller F, Joshi P, Yanek L, Trabetti E, Lehne B, Vozzi D, Verbanck M, Biino G, Saba Y, Meulenbelt I, O’Connell J, Laakso M, Giulianini F, Magnusson P, Ballantyne C, Hottenga J, Montgomery G, Rivadineira F, Rueedi R, Steri M, Herzig K, Stott D, Menni C, Frånberg M, St. Pourcain B, Felix S, Pers T, Bakker S, Kraft P, Peters A, Vaidya D, Delgado G, Smit J, Großmann V, Sinisalo J, Seppälä I, Williams S, Holliday E, Moed M, Langenberg C, Räikkönen K, Ding J, Campbell H, Sale M, Chen Y, James A, Ruggiero D, Soranzo N, Hartman C, Smith E, Berenson G, Fuchsberger C, Hernandez D, Tiesler C, Giedraitis V, Liewald D, Fischer K, Mellström D, Larsson A, Wang Y, Scott W, Lorentzon M, Beilby J, Ryan K, Pennell C, Vuckovic D, Balkau B, Concas M, Schmidt R, de Leon C, Bottinger E, Kloppenburg M, Paternoster L, Boehnke M, Musk A, Willemsen G, Evans D, Madden P, Kähönen M, Kutalik Z, Zoledziewska M, Karhunen V, Kritchevsky S, Sattar N, Lachance G, Clarke R, Harris T, Raitakari O, Attia J, van Heemst D, Kajantie E, Sorice R, Gambaro G, Scott R, Hicks A, Ferrucci L, Standl M, Lindgren C, Starr J, Karlsson M, Lind L, Li J, Chambers J, Mori T, de Geus E, Heath A, Martin N, Auvinen J, Buckley B, de Craen A, Waldenberger M, Strauch K, Meitinger T, Scott R, McEvoy M, Beekman M, Bombieri C, Ridker P, Mohlke K, Pedersen N, Morrison A, Boomsma D, Whitfield J, Strachan D, Hofman A, Vollenweider P, Cucca F, Jarvelin M, Jukema J, Spector T, Hamsten A, Zeller T, Uitterlinden A, Nauck M, Gudnason V, Qi L, Grallert H, Borecki I, Rotter J, März W, Wild P, Lokki M, Boyle M, Salomaa V, Melbye M, Eriksson J, Wilson J, Penninx B, Becker D, Worrall B, Gibson G, Krauss R, Ciullo M, Zaza G, Wareham N, Oldehinkel A, Palmer L, Murray S, Pramstaller P, Bandinelli S, Heinrich J, Ingelsson E, Deary I, Mägi R, Vandenput L, van der Harst P, Desch K, Kooner J, Ohlsson C, Hayward C, Lehtimäki T, Shuldiner A, Arnett D, Beilin L, Robino A, Froguel P, Pirastu M, Jess T, Koenig W, Loos R, Evans D, Schmidt H, Smith G, Slagboom E, Eiriksdottir G, Morris A, Psaty B, Tracy R, Nolte I, Boerwinkle E, Visvikis-Siest S, Reiner A, Gross M, Bis J, Franke L, Franco O, Benjamin E, Chasman D, Dupuis J, Snieder H, Dehghan A, Alizadeh B, Alizadeh B, Boezen H, Franke L, van der Harst P, Navis G, Rots M, Snieder H, Swertz M, Wolffenbuttel B, Wijmenga C, 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 P. Genome Analyses of >200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways that Link Inflammation and Complex Disorders. American Journal Of Human Genetics 2018, 103: 691-706. PMID: 30388399, PMCID: PMC6218410, DOI: 10.1016/j.ajhg.2018.09.009.Peer-Reviewed Original ResearchConceptsC-reactive proteinAmount of CRPGenome-wide association studiesMendelian randomization analysisClinical outcomesChronic inflammationChronic low-grade inflammationLow-grade inflammationRandomization analysisBody mass indexBiology of inflammationCausal protective effectDistinct genetic lociRisk-increasing effectSilico functional analysisMass indexProtective effectClinical consequencesMultiple complex diseasesImmune pathwaysInflammationBipolar disorderSensitive biomarkerGenome analysisHighlight pathwaysGenetic correlations among psychiatric and immune‐related phenotypes based on genome‐wide association data
Tylee DS, Sun J, Hess JL, Tahir MA, Sharma E, Malik R, Worrall BB, Levine AJ, Martinson JJ, Nejentsev S, Speed D, Fischer A, Mick E, Walker BR, Crawford A, Grant SFA, Polychronakos C, Bradfield JP, Sleiman PMA, Hakonarson H, Ellinghaus E, Elder JT, Tsoi LC, Trembath RC, Barker JN, Franke A, Dehghan A, Team T, Consortium T, Consortium T, Registry T, Group T, Consortium T, Faraone SV, Glatt SJ. Genetic correlations among psychiatric and immune‐related phenotypes based on genome‐wide association data. American Journal Of Medical Genetics Part B Neuropsychiatric Genetics 2018, 177: 641-657. PMID: 30325587, PMCID: PMC6230304, DOI: 10.1002/ajmg.b.32652.Peer-Reviewed Original ResearchConceptsImmune-related phenotypesPsychiatric disordersSystemic lupus erythematosusPrimary biliary cirrhosisLinkage disequilibrium score regressionImmune-related disordersAttention deficit hyperactivity disorderAutoimmune comorbiditiesDeficit hyperactivity disorderLupus erythematosusUlcerative colitisBiliary cirrhosisCrohn's diseaseObsessive-compulsive disorderMajor depressionImmunological stateSmoking behaviorTourette syndromeBipolar disorderAnorexia nervosaSummary-level dataEpidemiological literatureImmune signalingRespective disordersDisorders
2017
PTSD Blood Transcriptome Mega-Analysis: Shared Inflammatory Pathways across Biological Sex and Modes of Trauma
Breen MS, Tylee DS, Maihofer AX, Neylan TC, Mehta D, Binder EB, Chandler SD, Hess JL, Kremen WS, Risbrough VB, Woelk CH, Baker DG, Nievergelt CM, Tsuang MT, Buxbaum JD, Glatt SJ. PTSD Blood Transcriptome Mega-Analysis: Shared Inflammatory Pathways across Biological Sex and Modes of Trauma. Neuropsychopharmacology 2017, 43: 469-481. PMID: 28925389, PMCID: PMC5770765, DOI: 10.1038/npp.2017.220.Peer-Reviewed Original ResearchConceptsDistinct gene expression perturbationsCo-expression network analysisMitogen-activated protein kinase activityCommon signaling cascadesGene expression perturbationsProtein kinase activityTranscriptome-wide screenDistinct biological pathwaysMolecular convergenceGene expression signaturesTranscriptome studiesExpression perturbationsTranscriptional dysregulationSignaling cascadesKinase activityBiological pathwaysExpression signaturesType I interferonWidespread immune dysregulationInnate immuneLipid metabolismPathwayI interferonNetwork analysisDysregulationMachine-learning classification of 22q11.2 deletion syndrome: A diffusion tensor imaging study
Tylee DS, Kikinis Z, Quinn TP, Antshel KM, Fremont W, Tahir MA, Zhu A, Gong X, Glatt SJ, Coman IL, Shenton ME, Kates WR, Makris N. Machine-learning classification of 22q11.2 deletion syndrome: A diffusion tensor imaging study. NeuroImage Clinical 2017, 15: 832-842. PMID: 28761808, PMCID: PMC5522376, DOI: 10.1016/j.nicl.2017.04.029.Peer-Reviewed Original Research
2016
Blood transcriptomic comparison of individuals with and without autism spectrum disorder: A combined‐samples mega‐analysis
Tylee DS, Hess JL, Quinn TP, Barve R, Huang H, Zhang‐James Y, Chang J, Stamova BS, Sharp FR, Hertz‐Picciotto I, Faraone SV, Kong SW, Glatt SJ. Blood transcriptomic comparison of individuals with and without autism spectrum disorder: A combined‐samples mega‐analysis. American Journal Of Medical Genetics Part B Neuropsychiatric Genetics 2016, 174: 181-201. PMID: 27862943, PMCID: PMC5499528, DOI: 10.1002/ajmg.b.32511.Peer-Reviewed Original ResearchRNA sequencing of transformed lymphoblastoid cells from siblings discordant for autism spectrum disorders reveals transcriptomic and functional alterations: Evidence for sex‐specific effects
Tylee DS, Espinoza AJ, Hess JL, Tahir MA, McCoy SY, Rim JK, Dhimal T, Cohen OS, Glatt SJ. RNA sequencing of transformed lymphoblastoid cells from siblings discordant for autism spectrum disorders reveals transcriptomic and functional alterations: Evidence for sex‐specific effects. Autism Research 2016, 10: 439-455. PMID: 27529825, DOI: 10.1002/aur.1679.Peer-Reviewed Original ResearchConceptsTranscriptomic differencesGenome-wide expression studiesGene co-expression network analysisCo-expression network analysisTranscriptomic signaturesGene-set analysisStructural genetic variantsIdentified transcriptsGenomic studiesExpression studiesLymphoblastoid cell linesGenetic variantsCell linesExpression valuesNetwork analysisSignificant overlapGenesTranscriptsRNAASD studiesAutism spectrum disorderMale samplesLarge numberSignaturesFemales
2015
Gene networks specific for innate immunity define post-traumatic stress disorder
Breen MS, Maihofer AX, Glatt SJ, Tylee DS, Chandler SD, Tsuang MT, Risbrough VB, Baker DG, O'Connor DT, Nievergelt CM, Woelk CH. Gene networks specific for innate immunity define post-traumatic stress disorder. Molecular Psychiatry 2015, 20: 1538-1545. PMID: 25754082, PMCID: PMC4565790, DOI: 10.1038/mp.2015.9.Peer-Reviewed Original ResearchConceptsPost-traumatic stress disorderPTSD developmentStress disorderExpression of genesDevelopment of PTSDEarly preventative measuresPeripheral blood leukocytesInnate immune responseProper wound healingProspective experimental designClinical indicatorsRNA-seq gene expressionHemostatic systemBlood leukocytesInnate immuneCausal pathophysiologyMechanisms of PTSDCo-regulated genesInnate immunityPrevious transcriptomic studiesTrauma exposureCo-expression modulesU.S. MarinesPreventative measuresWound healing
2014
Blood-based gene-expression biomarkers of post-traumatic stress disorder among deployed marines: A pilot study
Tylee DS, Chandler SD, Nievergelt CM, Liu X, Pazol J, Woelk CH, Lohr JB, Kremen WS, Investigators M, Baker D, Glatt S, Tsuang M. Blood-based gene-expression biomarkers of post-traumatic stress disorder among deployed marines: A pilot study. Psychoneuroendocrinology 2014, 51: 472-494. PMID: 25311155, PMCID: PMC4199086, DOI: 10.1016/j.psyneuen.2014.09.024.Peer-Reviewed Original ResearchConceptsPost-traumatic stress disorderPeripheral bloodBiomarker panelStress disorderPilot studyPeripheral blood biomarkersHigh-risk individualsPeripheral blood samplesPeripheral blood cellsExpression levelsDiagnostic biomarker panelGene expression levelsTrauma-exposed individualsBlood biomarkersBlood samplesGene expression biomarkersBiomarker profilesDiagnostic utilityBrain tissueDiagnostic panelBlood cellsBloodFull-length gene transcriptsBiomarkersDisorders