Featured Publications
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
2021
Hematopoietic mosaic chromosomal alterations increase the risk for diverse types of infection
Zekavat SM, Lin SH, Bick AG, Liu A, Paruchuri K, Wang C, Uddin MM, Ye Y, Yu Z, Liu X, Kamatani Y, Bhattacharya R, Pirruccello JP, Pampana A, Loh PR, Kohli P, McCarroll SA, Kiryluk K, Neale B, Ionita-Laza I, Engels EA, Brown DW, Smoller JW, Green R, Karlson EW, Lebo M, Ellinor PT, Weiss ST, Daly MJ, Terao C, Zhao H, Ebert B, Reilly M, Ganna A, Machiela M, Genovese G, Natarajan P. Hematopoietic mosaic chromosomal alterations increase the risk for diverse types of infection. Nature Medicine 2021, 27: 1012-1024. PMID: 34099924, PMCID: PMC8245201, DOI: 10.1038/s41591-021-01371-0.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAged, 80 and overAgingBiological Specimen BanksChromosome AberrationsCommunicable DiseasesDigestive System DiseasesFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyGenotypeHematologic NeoplasmsHumansMaleMiddle AgedMosaicismPneumoniaRisk FactorsSepsisUrogenital AbnormalitiesYoung AdultConceptsMosaic chromosomal alterationsLeukocyte cell countDominant risk factorChromosomal alterationsBlood-derived DNAInfectious disease riskIncident infectionsSystem infectionGenitourinary infectionsImmune cellsRisk factorsHematological malignanciesHematological cancersCell countDisease riskInfectionInfectious diseasesClonal hematopoiesisSomatic variantsAgeRiskAlterationsWide association studyAutosomal mosaic chromosomal alterationsAssociation studiesInteractions Between Enhanced Polygenic Risk Scores and Lifestyle for Cardiovascular Disease, Diabetes, and Lipid Levels
Ye Y, Chen X, Han J, Jiang W, Natarajan P, Zhao H. Interactions Between Enhanced Polygenic Risk Scores and Lifestyle for Cardiovascular Disease, Diabetes, and Lipid Levels. Circulation Genomic And Precision Medicine 2021, 14: e003128. PMID: 33433237, PMCID: PMC7887077, DOI: 10.1161/circgen.120.003128.Peer-Reviewed Original ResearchConceptsType 2 diabetesAbsolute risk reductionPolygenic risk scoresLifestyle adherenceCardiovascular diseaseGenetic riskRisk scoreCoronary artery diseaseBody mass indexGreater absolute benefitHigher polygenic risk scoreHigh genetic riskAdditive interactionRisk reductionArtery diseaseLDL cholesterolTotal cholesterolAtrial fibrillationMass indexAbsolute benefitTriglyceride levelsRisk factorsLipid levelsPhysical activityLifestyle status
2020
Genome-wide association study of smoking trajectory and meta-analysis of smoking status in 842,000 individuals
Xu K, Li B, McGinnis KA, Vickers-Smith R, Dao C, Sun N, Kember RL, Zhou H, Becker WC, Gelernter J, Kranzler HR, Zhao H, Justice AC. Genome-wide association study of smoking trajectory and meta-analysis of smoking status in 842,000 individuals. Nature Communications 2020, 11: 5302. PMID: 33082346, PMCID: PMC7598939, DOI: 10.1038/s41467-020-18489-3.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesLarge genome-wide association studiesMillion Veteran ProgramAssociation studiesExpression quantitative trait lociQuantitative trait lociChromatin interactionsComplex traitsFunctional annotationTrait lociSequencing ConsortiumDozen genesSignificant lociSmoking phenotypesLociMultiple populationsNew insightsPhenotypeVeteran ProgramGenetic vulnerabilityGenesTraitsAnnotationEuropean AmericansConsortiumAutomated feature extraction from population wearable device data identified novel loci associated with sleep and circadian rhythms
Li X, Zhao H. Automated feature extraction from population wearable device data identified novel loci associated with sleep and circadian rhythms. PLOS Genetics 2020, 16: e1009089. PMID: 33075057, PMCID: PMC7595622, DOI: 10.1371/journal.pgen.1009089.Peer-Reviewed Original ResearchRelationship of Age With the Hemodynamic Parameters in Individuals With Elevated Blood Pressure
Mahajan S, Gu J, Caraballo C, Lu Y, Spatz ES, Zhao H, Zhang M, Sun N, Zheng X, Lu H, Yuan H, J. Z, Krumholz HM. Relationship of Age With the Hemodynamic Parameters in Individuals With Elevated Blood Pressure. Journal Of The American Geriatrics Society 2020, 68: 1520-1528. PMID: 32212398, DOI: 10.1111/jgs.16411.Peer-Reviewed Original ResearchConceptsElevated blood pressureBlood pressureCardiac indexHemodynamic profileHemodynamic parametersHealth checkup centerFinal study populationPathophysiology of hypertensionSelection of therapyCross-sectional studyMin/Relationship of ageDifferent age groupsHemodynamic assessmentMean ageStudy populationMAIN OUTCOMEAge strataAge groupsLarger studyImpedance cardiographyAgeSVRIWomenMen
2019
Gender Differences in Demographic and Health Characteristics of the Million Veteran Program Cohort
Harrington K, Nguyen X, Song R, Hannagan K, Quaden R, Gagnon D, Cho K, Deen J, Muralidhar S, O’Leary T, Gaziano J, Whitbourne S, Gaziano J, Ramoni R, Breeling J, Chang K, Huang G, Muralidhar S, O’Donnell C, Tsao P, Muralidhar S, Moser J, Whitbourne S, Brewer J, Concato J, Warren S, Pharm D, Argyres D, Tsao P, Gaziano J, Stephens B, Brophy M, Humphries D, Do N, Shayan S, Nguyen X, O’Donnell C, Pyarajan S, Tsao P, Cho K, Pyarajan S, Hauser E, Sun Y, Zhao H, Wilson P, McArdle R, Dellitalia L, Harley J, Whittle J, Beckham J, Wells J, Gutierrez S, Gibson G, Kaminsky L, Villareal G, Kinlay S, Xu J, Hamner M, Haddock K, Bhushan S, Iruvanti P, Godschalk M, Ballas Z, Buford M, Mastorides S, Klein J, Ratcliffe N, Florez H, Swann A, Murdoch M, Sriram P, Yeh S, Washburn R, Jhala D, Aguayo S, Cohen D, Sharma S, Callaghan J, Oursler K, Whooley M, Ahuja S, Gutierrez A, Schifman R, Greco J, Rauchman M, Servatius R, Oehlert M, Wallbom A, Fernando R, Morgan T, Stapley T, Sherman S, Anderson G, Tsao P, Sonel E, Boyko E, Meyer L, Gupta S, Fayad J, Hung A, Lichy J, Hurley R, Robey B, Striker R. Gender Differences in Demographic and Health Characteristics of the Million Veteran Program Cohort. Women's Health Issues 2019, 29: s56-s66. PMID: 31253243, PMCID: PMC7061933, DOI: 10.1016/j.whi.2019.04.012.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedCardiovascular DiseasesCohort StudiesFemaleHealth StatusHumansMaleMental DisordersMiddle AgedMigraine DisordersMusculoskeletal DiseasesPhysical FitnessPrevalenceSex DistributionSex FactorsSmokingSurveys and QuestionnairesUnited StatesUnited States Department of Veterans AffairsVeteransVeterans HealthYoung AdultConceptsMillion Veteran ProgramHealth characteristicsHealth statusSelf-reported health conditionsHealth conditionsHealth care characteristicsResearch participation ratesWomen Veteran populationExcellent health statusMillion Veteran Program cohortVeterans Health AdministrationPoor physical fitnessMental health disordersMVP cohortGender differencesSurvey completion rateResponder rateDecreased prevalenceMusculoskeletal conditionsMedical historyHigh cholesterolCardiovascular diseaseMigraine headacheCare characteristicsLifetime smokingGenome-wide Association Study of Maximum Habitual Alcohol Intake in >140,000 U.S. European and African American Veterans Yields Novel Risk Loci
Gelernter J, Sun N, Polimanti R, Pietrzak RH, Levey DF, Lu Q, Hu Y, Li B, Radhakrishnan K, Aslan M, Cheung KH, Li Y, Rajeevan N, Sayward F, Harrington K, Chen Q, Cho K, Honerlaw J, Pyarajan S, Lencz T, Quaden R, Shi Y, Hunter-Zinck H, Gaziano JM, Kranzler HR, Concato J, Zhao H, Stein MB, Program D, Program M. Genome-wide Association Study of Maximum Habitual Alcohol Intake in >140,000 U.S. European and African American Veterans Yields Novel Risk Loci. Biological Psychiatry 2019, 86: 365-376. PMID: 31151762, PMCID: PMC6919570, DOI: 10.1016/j.biopsych.2019.03.984.Peer-Reviewed Original ResearchConceptsAdditional genome-wide significant lociRisk lociWide association study (GWAS) analysisAssociation studiesGenome-wide significant lociGenome-wide association studiesGenetic correlationsWide association studyNovel risk lociAlcohol-related traitsStrong statistical supportSmoking-related traitsAdditional genomesSignificant lociPancreatic delta cellsChromosome 4Chromosome 11Protein productsChromosome 8Quantitative phenotypesMillion Veteran ProgramVeterans Affairs Million Veteran ProgramLociCell typesChromosome 17Genome-wide association study of alcohol consumption and use disorder in 274,424 individuals from multiple populations
Kranzler HR, Zhou H, Kember RL, Vickers Smith R, Justice AC, Damrauer S, Tsao PS, Klarin D, Baras A, Reid J, Overton J, Rader DJ, Cheng Z, Tate JP, Becker WC, Concato J, Xu K, Polimanti R, Zhao H, Gelernter J. Genome-wide association study of alcohol consumption and use disorder in 274,424 individuals from multiple populations. Nature Communications 2019, 10: 1499. PMID: 30940813, PMCID: PMC6445072, DOI: 10.1038/s41467-019-09480-8.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesAssociation studiesMillion Veteran Program sampleGenetic correlationsWide significant lociSignificant genetic correlationsPolygenic risk scoresCell type groupSignificant lociHeritable traitEnrichment analysisTraitsMultiple populationsLociPhenotypeProgram samples
2018
Effects of Genetic Variants Associated with Familial Hypercholesterolemia on Low-Density Lipoprotein-Cholesterol Levels and Cardiovascular Outcomes in the Million Veteran Program
Sun Y, Damrauer S, Hui Q, Assimes T, Ho Y, Natarajan P, Klarin D, Huang J, Lynch J, DuVall S, Pyarajan S, Honerlaw J, Gaziano J, Cho K, Rader D, O’Donnell C, Tsao P, Wilson P, Ramoni R, Breeling J, Chang K, Huang G, Muralidhar S, Muralidhar S, Moser J, Whitbourne S, Brewer J, Concato J, Warren S, Argyres D, Stephens B, Brophy M, Humphries D, Do N, Shayan S, Nguyen X, Hauser E, Sun Y, Zhao H, Wilson P, McArdle R, Dellitalia L, Harley J, Whittle J, Beckham J, Wells J, Gutierrez S, Gibson G, Kaminsky L, Villareal G, Kinlay S, Xu J, Hamner M, Haddock K, Bhushan S, Iruvanti P, Godschalk M, Ballas Z, Buford M, Mastorides S, Klein J, Ratcliffe N, Florez H, Swann A, Murdoch M, Sriram P, Yeh S, Washburn R, Jhala D, Aguayo S, Cohen D, Sharma S, Callaghan J, Oursler K, Whooley M, Ahuja S, Gutierrez A, Schifman R, Greco J, Rauchman M, Servatius R, Oehlert M, Wallbom A, Fernando R, Morgan T, Stapley T, Sherman S, Anderson G, Tsao P, Sonel E, Boyko E, Meyer L, Gupta S, Fayad J, Hung A, Lichy J, Hurley R, Robey B, Striker R. Effects of Genetic Variants Associated with Familial Hypercholesterolemia on Low-Density Lipoprotein-Cholesterol Levels and Cardiovascular Outcomes in the Million Veteran Program. Circulation Genomic And Precision Medicine 2018, 11 PMID: 31106297, PMCID: PMC6516478, DOI: 10.1161/circgen.118.002192.Peer-Reviewed Original ResearchConceptsCoronary heart diseasePathogenic FH variantsFamilial hypercholesterolemiaFH variantsClinical outcomesHigh prevalenceLow-density lipoprotein cholesterolPremature coronary heart diseasePeripheral artery diseaseLDL-C levelsLow-density lipoproteinMulti-ethnic populationCardiovascular outcomesArtery diseaseLipoprotein cholesterolCholesterol levelsHeart diseaseMillion Veteran ProgramRisk individualsPhenome-wide scanGenetic Variants AssociatedClinical diagnosisClinical encountersHypercholesterolemiaMulti-ethnic participantsTranslational studies support a role for serotonin 2B receptor (HTR2B) gene in aggression-related cannabis response
Montalvo-Ortiz JL, Zhou H, D’Andrea I, Maroteaux L, Lori A, Smith A, Ressler KJ, Nuñez YZ, Farrer LA, Zhao H, Kranzler HR, Gelernter J. Translational studies support a role for serotonin 2B receptor (HTR2B) gene in aggression-related cannabis response. Molecular Psychiatry 2018, 23: 2277-2286. PMID: 29875475, PMCID: PMC6281782, DOI: 10.1038/s41380-018-0077-6.Peer-Reviewed Original ResearchConceptsGrady Trauma ProjectAfrican AmericansWild-type miceReceptor geneEffects of cannabisWide significant risk lociResident-intruder paradigmImpulsivity/aggressionConcordant findingsTHC administrationKnockout miceTranslational studiesAA subjectsCannabis useStudy designTrauma ProjectAdverse effectsMiceCannabisAggressive behaviorEuropean AmericansNominal associationAdverse consequencesGenome-wide association study (GWAS) designRisk loci
2017
Genetic Risk Variants Associated With Comorbid Alcohol Dependence and Major Depression
Zhou H, Polimanti R, Yang BZ, Wang Q, Han S, Sherva R, Nuñez YZ, Zhao H, Farrer LA, Kranzler HR, Gelernter J. Genetic Risk Variants Associated With Comorbid Alcohol Dependence and Major Depression. JAMA Psychiatry 2017, 74: 1234-1241. PMID: 29071344, PMCID: PMC6331050, DOI: 10.1001/jamapsychiatry.2017.3275.Peer-Reviewed Original ResearchMeSH KeywordsAdultAlcoholismBlack or African AmericanComorbidityDepressive Disorder, MajorDiagnostic and Statistical Manual of Mental DisordersFemaleGenetic Predisposition to DiseaseGenetic VariationHumansMaleMiddle AgedMultifactorial InheritanceOrgan SizePutamenSemaphorin-3AUnited StatesWhite PeopleConceptsGenome-wide association studiesGenetic risk variantsNeuropsychiatric traitsAssociation studiesRisk variantsPolygenic risk allelesPolygenic risk scoresGenetic mechanismsGenetic basisAmerican data setMolecular natureTraitsCriterion countsGenetic causePossible genetic causesMD comorbidityRisk allelesComorbid alcohol dependence