2022
Understanding 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
Sex-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
2019
Transcriptomic abnormalities in peripheral blood in bipolar disorder, and discrimination of the major psychoses
Hess JL, Tylee DS, Barve R, de Jong S, Ophoff RA, Kumarasinghe N, Tooney P, Schall U, Gardiner E, Beveridge NJ, Scott RJ, Yasawardene S, Perera A, Mendis J, Carr V, Kelly B, Cairns M, Unit T, Tsuang MT, Glatt SJ. Transcriptomic abnormalities in peripheral blood in bipolar disorder, and discrimination of the major psychoses. Schizophrenia Research 2019, 217: 124-135. PMID: 31391148, PMCID: PMC6997041, DOI: 10.1016/j.schres.2019.07.036.Peer-Reviewed Original ResearchConceptsGene modulesSZ casesGene co-expression network analysisCo-expression network analysisGene expression profilesGene expression alterationsChromatin regulationChromatin remodelingNineteen genesGene networksTranscriptomic abnormalitiesDisorder-specific changesGene expressionExpression profilesBiological processesImmune signalingExpression alterationsTranscriptomic signaturesGenesReactive oxygenUnaffected comparison subjectsMajor psychosesOxidative stressBD casesApoptosis
2016
RNA 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 numberSignaturesFemalesTranscriptome-wide mega-analyses reveal joint dysregulation of immunologic genes and transcription regulators in brain and blood in schizophrenia
Hess JL, Tylee DS, Barve R, de Jong S, Ophoff RA, Kumarasinghe N, Tooney P, Schall U, Gardiner E, Beveridge NJ, Scott RJ, Yasawardene S, Perera A, Mendis J, Carr V, Kelly B, Cairns M, Unit T, Tsuang MT, Glatt SJ. Transcriptome-wide mega-analyses reveal joint dysregulation of immunologic genes and transcription regulators in brain and blood in schizophrenia. Schizophrenia Research 2016, 176: 114-124. PMID: 27450777, PMCID: PMC5026943, DOI: 10.1016/j.schres.2016.07.006.Peer-Reviewed Original ResearchConceptsGene co-expression modulesMicroarray dataCo-expression modulesInnate immune gene expressionRelated gene setsImmune gene expressionTranscription regulatorsNetwork-based analysisGene setsBiological functionsGene expressionRegulatory factorsPostmortem prefrontal cortexMicroarray technologyCell typesTop hitsHigh-throughput assessmentGenesTissue functionBlood tissuePostmortem brain tissueGenetic risk factorsImmunologic genesMicroarray literatureDysregulation
2013
On the outside, looking in: A review and evaluation of the comparability of blood and brain “‐omes”
Tylee DS, Kawaguchi DM, Glatt SJ. On the outside, looking in: A review and evaluation of the comparability of blood and brain “‐omes”. American Journal Of Medical Genetics Part B Neuropsychiatric Genetics 2013, 162: 595-603. PMID: 24132893, DOI: 10.1002/ajmg.b.32150.Peer-Reviewed Original ResearchConceptsCpG island methylation levelsCross-tissue correlationBlood-based biomarker studiesTranscriptomic studiesDNA methylationOmics analysisGene expressionMethylation levelsBlood tissue samplesExpression levelsProtein expressionProfiling methodExpressionEpigenomeTranscriptomeProteomeGenesMethylationTranscriptsTissue samplesValidation of biomarkersBetter understandingCritical precursorPatternsParticular subset