Featured Publications
Genetic 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 smokingGenome-Wide Methylation of Mild Cognitive Impairment in Mexican Americans Highlights Genes Involved in Synaptic Transport, Alzheimer's Disease-Precursor Phenotypes, and Metabolic Morbidities.
Pathak GA, Silzer TK, Sun J, Zhou Z, Daniel AA, Johnson L, O'Bryant S, Phillips NR, Barber RC. Genome-Wide Methylation of Mild Cognitive Impairment in Mexican Americans Highlights Genes Involved in Synaptic Transport, Alzheimer's Disease-Precursor Phenotypes, and Metabolic Morbidities. Journal Of Alzheimer's Disease 2019, 72: 733-749. PMID: 31640099, DOI: 10.3233/jad-190634.Peer-Reviewed Original Research
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 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. 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
Sex-Specific Genetic and Transcriptomic Liability to Neuroticism
Wendt FR, Pathak GA, Singh K, Stein MB, Koenen KC, Krystal JH, Gelernter J, Davis LK, Polimanti R. Sex-Specific Genetic and Transcriptomic Liability to Neuroticism. Biological Psychiatry 2022, 93: 243-252. PMID: 36244801, PMCID: PMC10508260, DOI: 10.1016/j.biopsych.2022.07.019.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesTranscriptomic profilesAssociation studiesSingle nucleotide polymorphism heritabilityGene expression variationGenome-wide significanceSex-specific geneticChromosomal variationTranscriptomic changesRisk lociExpression variationBiological processesMolecular pathwaysLociPolygenic associationSex-specific effectsGenetic correlatesPolygenic scoresUK BiobankGenetic riskNCOA6GeneticsHeritabilityPathwayFemalesUsing 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
Bi-ancestral depression GWAS in the Million Veteran Program and meta-analysis in >1.2 million individuals highlight new therapeutic directions
Levey DF, Stein MB, Wendt FR, Pathak GA, Zhou H, Aslan M, Quaden R, Harrington KM, Nuñez YZ, Overstreet C, Radhakrishnan K, Sanacora G, McIntosh AM, Shi J, Shringarpure SS, Concato J, Polimanti R, Gelernter J. Bi-ancestral depression GWAS in the Million Veteran Program and meta-analysis in >1.2 million individuals highlight new therapeutic directions. Nature Neuroscience 2021, 24: 954-963. PMID: 34045744, PMCID: PMC8404304, DOI: 10.1038/s41593-021-00860-2.Peer-Reviewed Original ResearchConceptsTranscriptome-wide association studyMillion Veteran ProgramTranscriptome-wide association study (TWAS) analysisGenomic risk lociComplex psychiatric traitsGenetic architectureRisk lociGene expressionAssociation studiesLikely pathogenicityPsychiatric traitsVeteran ProgramNew therapeutic directionEuropean ancestryNew insightsAncestryUK BiobankAfrican ancestrySubstantial replicationExpressionLarge independent cohortsGWASTherapeutic directionsGenesLociBiobank Scale Pharmacogenomics Informs the Genetic Underpinnings of Simvastatin Use
Wendt FR, Koller D, Pathak GA, Jacoby D, Miller EJ, Polimanti R. Biobank Scale Pharmacogenomics Informs the Genetic Underpinnings of Simvastatin Use. Clinical Pharmacology & Therapeutics 2021, 110: 777-785. PMID: 33837531, PMCID: PMC8376807, DOI: 10.1002/cpt.2260.Peer-Reviewed Original ResearchConceptsLDL-C concentrationsSimvastatin useLow-density lipoprotein cholesterol concentrationsLipoprotein cholesterol concentrationsDrug-metabolizing enzymesElectronic medical recordsStatin therapyStatin treatmentActivity scoreMedical recordsPilot cohortCholesterol concentrationsEuropean ancestry participantsMetabolizer phenotypeClinical decisionNAT2 allelesPolygenic riskNAT2Good responseUK BiobankBiological mechanismsPharmacogenesAssociationPotential benefitsPhenotypeMultiomics Investigation of Hypertension and White Matter Hyperintensity as a Source of Vascular Dementia or a Comorbidity to Alzheimer’s Disease
Pathak G, Barber R, Phillips N. Multiomics Investigation of Hypertension and White Matter Hyperintensity as a Source of Vascular Dementia or a Comorbidity to Alzheimer’s Disease. Current Alzheimer Research 2021, 18: 171-177. PMID: 33888050, DOI: 10.2174/1567205018666210422133547.Peer-Reviewed Original ResearchConceptsVascular dementiaAlzheimer's diseaseAbsence of imagingP-tau levelsAge-related comorbiditiesPrevalent age-related conditionProbable vascular dementiaWhite matter hyperintensitiesAge-related conditionsP-tauCSF levelsCSF biomarkersRisk factorsHealthy controlsSignificant gene expression changesClinical dataDifferential diagnosisMatter hyperintensitiesHypertensionAmyloid βUnaffected control populationControl populationMultiomics investigationsDementia profileDiagnostic tests
2020
Epigenetic profiling of Italian patients identified methylation sites associated with hereditary transthyretin amyloidosis
De Lillo A, Pathak GA, De Angelis F, Di Girolamo M, Luigetti M, Sabatelli M, Perfetto F, Frusconi S, Manfellotto D, Fuciarelli M, Polimanti R. Epigenetic profiling of Italian patients identified methylation sites associated with hereditary transthyretin amyloidosis. Clinical Epigenetics 2020, 12: 176. PMID: 33203445, PMCID: PMC7672937, DOI: 10.1186/s13148-020-00967-6.Peer-Reviewed Original ResearchConceptsEpigenome-wide association studiesMethylation sitesEpigenetic differencesSignificant epigenetic differencesProtein interaction networksSignificant methylation changesAmyloidogenic mutationsDisease-causing mutationsProtein interactorsEpigenetic regulationHigh phenotypic variabilityEpigenetic profilingMethylation changesInteraction networksGene regionBiological processesMolecular mechanismsAssociation studiesMolecular pathwaysCoding mutationsPhenotypic variabilityNovel insightsGenesFiber formationMutationsPolygenic risk for autism spectrum disorder associates with anger recognition in a neurodevelopment-focused phenome-wide scan of unaffected youths from a population-based cohort
Wendt FR, Carvalho CM, Pathak GA, Gelernter J, Polimanti R. Polygenic risk for autism spectrum disorder associates with anger recognition in a neurodevelopment-focused phenome-wide scan of unaffected youths from a population-based cohort. PLOS Genetics 2020, 16: e1009036. PMID: 32941431, PMCID: PMC7523983, DOI: 10.1371/journal.pgen.1009036.Peer-Reviewed Original ResearchPatient genetics is linked to chronic wound microbiome composition and healing
Tipton C, Wolcott R, Sanford N, Miller C, Pathak G, Silzer T, Sun J, Fleming D, Rumbaugh K, Little T, Phillips N, Phillips C. Patient genetics is linked to chronic wound microbiome composition and healing. PLOS Pathogens 2020, 16: e1008511. PMID: 32555671, PMCID: PMC7302439, DOI: 10.1371/journal.ppat.1008511.Peer-Reviewed Original ResearchConceptsFocal adhesionsMicrobiome genome-wide association studyPatient's genetic determinantsMicrobiome diversityChronic wound microbiomeWide association studyMicrobiome compositionWound microbiomeGenomic lociCytoskeletal dynamicsBacterial exploitationGenetic variationAlternative transcriptsExpression differencesChronicity of woundsAssociation studiesAdhesion phenotypePseudomonas aeruginosaCellular migrationRelative abundanceGenetic determinantsSignificant inter-patient variationLociDiversityGenetic ancestryMitochondrial tRNA methylation in Alzheimer’s disease and progressive supranuclear palsy
Silzer T, Pathak G, Phillips N. Mitochondrial tRNA methylation in Alzheimer’s disease and progressive supranuclear palsy. BMC Medical Genomics 2020, 13: 71. PMID: 32429992, PMCID: PMC7236490, DOI: 10.1186/s12920-020-0727-9.Peer-Reviewed Original ResearchConceptsNuclear gene expressionGene-based association studyMitochondrial dysfunctionPost-transcriptional methylationRNA-seq dataSimilar expression profilesPotential molecular underpinningsNeurodegenerative disease pathophysiologyNuclear genesTOP transcriptsSequence-based methodsMitochondrial tRNAsTranslational efficiencyEnrichment testingContext of cancerGene expressionTRNA methylationDegree of methylationExpression profilesBiological processesAssociation studiesMolecular underpinningsMolecular processesMethylationMitochondrial function
2019
Circulating mitochondrial DNA: New indices of type 2 diabetes-related cognitive impairment in Mexican Americans
Silzer T, Barber R, Sun J, Pathak G, Johnson L, O’Bryant S, Phillips N. Circulating mitochondrial DNA: New indices of type 2 diabetes-related cognitive impairment in Mexican Americans. PLOS ONE 2019, 14: e0213527. PMID: 30861027, PMCID: PMC6414026, DOI: 10.1371/journal.pone.0213527.Peer-Reviewed Original ResearchConceptsComplex age-related diseasesCognitive impairmentAlzheimer's diseaseAge-related diseasesMitochondrial DNADiabetes-related cognitive impairmentType 2 diabetesCell-free mitochondrial DNACommon pathophysiological characteristicsSingle significant locusPotential roleLeucine-rich repeat kinase 2Mexican AmericansMexican American cohortMitochondrial DNA copy numberDisease exacerbationIndicators of diseaseRepeat kinase 2Total recall scoresPathophysiological characteristicsDisease progressionCI phenotypeDNA copy numberParkinson's diseaseSignificant loci