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
2024
Phenome- and genome-wide analyses of retinal optical coherence tomography images identify links between ocular and systemic health
Zekavat S, Jorshery S, Rauscher F, Horn K, Sekimitsu S, Koyama S, Nguyen T, Costanzo M, Jang D, Burtt N, Kühnapfel A, Shweikh Y, Ye Y, Raghu V, Zhao H, Ghassemi M, Elze T, Segrè A, Wiggs J, Del Priore L, Scholz M, Wang J, Natarajan P, Zebardast N. Phenome- and genome-wide analyses of retinal optical coherence tomography images identify links between ocular and systemic health. Science Translational Medicine 2024, 16: eadg4517. PMID: 38266105, DOI: 10.1126/scitranslmed.adg4517.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesRetinal layer thicknessPhotoreceptor segmentsOptical coherence tomographyRetinal layersUK Biobank participantsLIFE-Adult-StudyInherited genetic lociGenome-wide associationGanglion cell complex layerRetinal optical coherence tomography imagesRetinal nerve fiber layerAge-related macular degenerationBiobank participantsEye careNerve fiber layerOptical coherence tomography imagesIncident mortalityMacular OCT imagesLIFE-AdultIndependent associationsAssociation studiesSystemic healthGenetic associationGenome-wide analysis
2022
Sex-specific genetic association between psychiatric disorders and cognition, behavior and brain imaging in children and adults
Gui Y, Zhou X, Wang Z, Zhang Y, Wang Z, Zhou G, Zhao Y, Liu M, Lu H, Zhao H. Sex-specific genetic association between psychiatric disorders and cognition, behavior and brain imaging in children and adults. Translational Psychiatry 2022, 12: 347. PMID: 36028495, PMCID: PMC9418275, DOI: 10.1038/s41398-022-02041-6.Peer-Reviewed Original ResearchConceptsCognitive functionFluid intelligenceCognitive traitsAdolescent Brain Cognitive Development (ABCD) studyPsychiatric disordersCognitive Development StudyMediation effectMost psychiatric disordersPolygenic risk scoresBrain functionBrain structuresBrain imagingEarly etiologySex differencesDevelopment studiesPsychiatric traitsChildrenIntelligenceDisordersSchizophreniaGenetic riskAdultsTraitsCognitionAutism
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
2019
Genome-wide association study of post-traumatic stress disorder reexperiencing symptoms in >165,000 US veterans
Gelernter J, Sun N, Polimanti R, Pietrzak R, Levey DF, Bryois J, Lu Q, Hu Y, Li B, Radhakrishnan K, Aslan M, Cheung KH, Li Y, Rajeevan N, Sayward F, Harrington K, Chen Q, Cho K, Pyarajan S, Sullivan PF, Quaden R, Shi Y, Hunter-Zinck H, Gaziano JM, Concato J, Zhao H, Stein MB. Genome-wide association study of post-traumatic stress disorder reexperiencing symptoms in >165,000 US veterans. Nature Neuroscience 2019, 22: 1394-1401. PMID: 31358989, PMCID: PMC6953633, DOI: 10.1038/s41593-019-0447-7.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesAssociation studiesHigh linkage disequilibrium regionLinkage disequilibrium regionWide association studyDisequilibrium regionBioinformatics analysisTranscriptomic profilesMillion Veteran ProgramChromosome 17Genetic risk factorsNew insightsUK Biobank dataReexperiencing of traumaStriatal medium spiny neuronsVeteran ProgramSignificant regionsCAMKVEuropean AmericansBiobank dataMedium spiny neuronsTCF4BiologyKANSL1African American cohortGender 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
2001
The Power of Transmission Disequilibrium Tests for Quantitative Traits
Li J, Wang D, Dong J, Jiang R, Zhang K, Zhang S, Zhao H, Sun F. The Power of Transmission Disequilibrium Tests for Quantitative Traits. Genetic Epidemiology 2001, 21: s632-s637. PMID: 11793752, DOI: 10.1002/gepi.2001.21.s1.s632.Peer-Reviewed Original Research