2024
Tuning parameters for polygenic risk score methods using GWAS summary statistics from training data
Jiang W, Chen L, Girgenti M, Zhao H. Tuning parameters for polygenic risk score methods using GWAS summary statistics from training data. Nature Communications 2024, 15: 24. PMID: 38169469, PMCID: PMC10762162, DOI: 10.1038/s41467-023-44009-0.Peer-Reviewed Original Research
2023
Integrating genetics and transcriptomics to study major depressive disorder: a conceptual framework, bioinformatic approaches, and recent findings
Hicks E, Seah C, Cote A, Marchese S, Brennand K, Nestler E, Girgenti M, Huckins L. Integrating genetics and transcriptomics to study major depressive disorder: a conceptual framework, bioinformatic approaches, and recent findings. Translational Psychiatry 2023, 13: 129. PMID: 37076454, PMCID: PMC10115809, DOI: 10.1038/s41398-023-02412-7.Peer-Reviewed Original ResearchMeSH KeywordsBrainComputational BiologyDepressive Disorder, MajorGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansTranscriptomeConceptsBioinformatics approachTranscriptomic dataBrain transcriptomeGenome-wide analysisDynamic transcriptional landscapeBrain gene expression dataGene expression dataTranscriptional landscapeTranscriptomic studiesIntegrating GeneticExpression dataPhenotypic signaturesGenomic driversTranscriptomeMajor depressive disorderValuable resourceRecent findingsEnvironmental influencesTranscriptomicsDepressive disorderGeneticsMultiple approachesPathophysiology of depressionSignaturesDysregulation
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 ResearchMeSH KeywordsFemaleGenome-Wide Association StudyHumansMaleRisk FactorsSuicidal IdeationSuicide, AttemptedVeteransConceptsPolygenic 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 levelsVeteransSuicidalityEpigenome-wide association study of posttraumatic stress disorder identifies novel loci in U.S. military veterans
Montalvo-Ortiz JL, Gelernter J, Cheng Z, Girgenti MJ, Xu K, Zhang X, Gopalan S, Zhou H, Duman RS, Southwick SM, Krystal JH, Pietrzak R. Epigenome-wide association study of posttraumatic stress disorder identifies novel loci in U.S. military veterans. Translational Psychiatry 2022, 12: 65. PMID: 35177594, PMCID: PMC8854688, DOI: 10.1038/s41398-022-01822-3.Peer-Reviewed Original ResearchMeSH KeywordsDNA MethylationEpigenomeGenome-Wide Association StudyHumansMaleStress Disorders, Post-TraumaticVeteransConceptsEpigenome-wide association studiesAssociation studiesTranscription regulationCpG sitesGenome-wide association studiesCell type proportionsPosttraumatic stress disorderPotential epigenetic biomarkersSignificant CpG sitesEpigenetic mechanismsDNA methylationNovel lociCell signalingEpigenetic biomarkersMethylation analysisAxonal guidanceNovel molecular biomarkersEPIC BeadChipLifetime posttraumatic stress disorderMilitary veteransPostmortem brain tissueMedial orbitofrontal cortexMolecular biomarkersRegulationU.S. military veterans
2021
Genome-wide association analyses of post-traumatic stress disorder and its symptom subdomains in the Million Veteran Program
Stein MB, Levey DF, Cheng Z, Wendt FR, Harrington K, Pathak GA, Cho K, Quaden R, Radhakrishnan K, Girgenti MJ, Ho YA, Posner D, Aslan M, Duman RS, Zhao H, Polimanti R, Concato J, Gelernter J. Genome-wide association analyses of post-traumatic stress disorder and its symptom subdomains in the Million Veteran Program. Nature Genetics 2021, 53: 174-184. PMID: 33510476, PMCID: PMC7972521, DOI: 10.1038/s41588-020-00767-x.Peer-Reviewed Original ResearchConceptsGenome-wide association analysisAssociation analysisMillion Veteran ProgramGenomic structural equation modelingSignificant lociGenetic varianceGene expressionDrug repositioning candidatesBiological coherenceVeteran ProgramMultiple testing correctionSymptom phenotypeLociRepositioning candidatesAfrican ancestryHeritabilityPhenotypeAncestryExpressionPTSD symptom factorsRegionSubdomainsEnrichment
2020
Transcriptomic organization of the human brain in post-traumatic stress disorder
Girgenti MJ, Wang J, Ji D, Cruz DA, Stein M, Gelernter J, Young K, Huber B, Williamson D, Friedman M, Krystal J, Zhao H, Duman R. Transcriptomic organization of the human brain in post-traumatic stress disorder. Nature Neuroscience 2020, 24: 24-33. PMID: 33349712, DOI: 10.1038/s41593-020-00748-7.Peer-Reviewed Original ResearchMeSH KeywordsAdultAutopsyBrain ChemistryCohort StudiesDepressive Disorder, MajorFemaleGene Expression RegulationGene Regulatory NetworksGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansInterneuronsMaleMiddle AgedNerve Tissue ProteinsSex CharacteristicsStress Disorders, Post-TraumaticTranscriptomeYoung AdultConceptsGenome-wide association studiesSignificant gene networksDifferential gene expressionSystems-level evidenceSignificant genetic liabilityMajor depressive disorder cohortGene networksTranscriptomic organizationTranscriptomic landscapeDownregulated setsGenomic networksGene expressionAssociation studiesMolecular determinantsExtensive remodelingGenotype dataSexual dimorphismSignificant divergenceMolecular profileNetwork analysisELFN1TranscriptsDimorphismPostmortem tissueDivergence
2012
ZNF804a Regulates Expression of the Schizophrenia-Associated Genes PRSS16, COMT, PDE4B, and DRD2
Girgenti MJ, LoTurco JJ, Maher BJ. ZNF804a Regulates Expression of the Schizophrenia-Associated Genes PRSS16, COMT, PDE4B, and DRD2. PLOS ONE 2012, 7: e32404. PMID: 22384243, PMCID: PMC3288100, DOI: 10.1371/journal.pone.0032404.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBinding SitesCatechol O-MethyltransferaseCell NucleusCyclic Nucleotide Phosphodiesterases, Type 4Gene Expression ProfilingGene Expression RegulationGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansImmunohistochemistryKruppel-Like Transcription FactorsRatsReceptors, Dopamine D2Recombinant ProteinsSchizophreniaSerine EndopeptidasesStem CellsTranscription, GeneticConceptsC2H2-type zinc finger domainsTranscript levelsPromoter regionGenome-wide statistical significanceZinc finger domainChromatin immunoprecipitation assaysWide association studyAmino acid sequenceRat neural progenitor cellsNeural progenitor cellsTranscriptional networksMolecular functionsTranscriptional controlSingle nucleotide polymorphismsImmunoprecipitation assaysDNA bindingAcid sequenceTranscription levelsAssociation studiesGenesNucleotide polymorphismsProgenitor cellsZNF804ATranscriptionDirect upregulation
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