Featured Publications
Genome-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 samplesGenome-wide association study identifies glutamate ionotropic receptor GRIA4 as a risk gene for comorbid nicotine dependence and major depression
Zhou H, Cheng Z, Bass N, Krystal JH, Farrer LA, Kranzler HR, Gelernter J. Genome-wide association study identifies glutamate ionotropic receptor GRIA4 as a risk gene for comorbid nicotine dependence and major depression. Translational Psychiatry 2018, 8: 208. PMID: 30287806, PMCID: PMC6172277, DOI: 10.1038/s41398-018-0258-8.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesGenome-wide association study identifiesRisk genesTop risk genesCalcium ion bindingGenomes reference panelFast excitatory synaptic transmissionGenetic risk variantsGenetic basisEnrichment analysisAssociation studiesExome arrayCell adhesionRisk variantsGenesReference panelGenetic riskAMPA-sensitive glutamate receptorsIntronic variantsIon bindingBiological mechanismsConditional analysisGRIA4Excitatory synaptic transmissionSynaptic transmissionTranslational 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 lociGenetic 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 dependencePolygenic Scores for Major Depressive Disorder and Risk of Alcohol Dependence
Andersen AM, Pietrzak RH, Kranzler HR, Ma L, Zhou H, Liu X, Kramer J, Kuperman S, Edenberg HJ, Nurnberger JI, Rice JP, Tischfield JA, Goate A, Foroud TM, Meyers JL, Porjesz B, Dick DM, Hesselbrock V, Boerwinkle E, Southwick SM, Krystal JH, Weissman MM, Levinson DF, Potash JB, Gelernter J, Han S. Polygenic Scores for Major Depressive Disorder and Risk of Alcohol Dependence. JAMA Psychiatry 2017, 74: 1153-1160. PMID: 28813562, PMCID: PMC5710224, DOI: 10.1001/jamapsychiatry.2017.2269.Peer-Reviewed Original ResearchConceptsMDD polygenic risk scoresMajor depressive disorderPolygenic risk scoresAlcohol dependenceDepressive disorderSignificant public health burdenPublic health burdenAD comorbidityNational HealthHealth burdenMAIN OUTCOMECase-control statusRisk scoreRisk of ADVeterans StudyYale-PennGenetic susceptibilityMDD statusCommon genetic factorsSubstance dependenceMDD casesAD samplesPolygenic riskGenetic factorsHeritable disorder
2023
Genome-wide association studies and cross-population meta-analyses investigating short and long sleep duration
Austin-Zimmerman I, Levey D, Giannakopoulou O, Deak J, Galimberti M, Adhikari K, Zhou H, Denaxas S, Irizar H, Kuchenbaecker K, McQuillin A, Concato J, Buysse D, Gaziano J, Gottlieb D, Polimanti R, Stein M, Bramon E, Gelernter J. Genome-wide association studies and cross-population meta-analyses investigating short and long sleep duration. Nature Communications 2023, 14: 6059. PMID: 37770476, PMCID: PMC10539313, DOI: 10.1038/s41467-023-41249-y.Peer-Reviewed Original ResearchConceptsAssociation studiesGenome-wide association studiesGenetic correlationsWide association studyLinkage disequilibrium scorePositive genetic correlationSleep traitsIndependent lociMillion Veteran ProgramTraitsAncestryUK BiobankVeteran ProgramMendelian randomisationLociHeritabilitySNPsPhenotypeEast AsiansSimilar patternCardiometabolic phenotypes
2019
Genomewide Gene-by-Sex Interaction Scans Identify ADGRV1 for Sex Differences in Opioid Dependent African Americans
Yang BZ, Zhou H, Cheng Z, Kranzler HR, Gelernter J. Genomewide Gene-by-Sex Interaction Scans Identify ADGRV1 for Sex Differences in Opioid Dependent African Americans. Scientific Reports 2019, 9: 18070. PMID: 31792237, PMCID: PMC6889277, DOI: 10.1038/s41598-019-53560-0.Peer-Reviewed Original ResearchMeSH KeywordsAdultAllelesAnalgesics, OpioidBlack or African AmericanBrainCalcium-Binding ProteinsFemaleGene Expression ProfilingGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMaleMiddle AgedOpioid-Related DisordersPolymorphism, Single NucleotideReceptors, G-Protein-CoupledReceptors, Kainic AcidSex FactorsWhite PeopleConceptsOpioid dependenceOD riskSex-different effectsSex differencesInferior olivary nucleusDSM-IV diagnosisDimorphic riskSubstantia nigraAA menOlivary nucleusFrontal cortexEuropean-American subjectsADGRV1Further studiesRiskAfrican AmericansGenetic variantsDisease enrichment analysisBrainSex interactionNominal significanceMenFirst studyPutamenLungGenome-wide association study of alcohol dependence in male Han Chinese and cross-ethnic polygenic risk score comparison
Sun Y, Chang S, Wang F, Sun H, Ni Z, Yue W, Zhou H, Gelernter J, Malison RT, Kalayasiri R, Wu P, Lu L, Shi J. Genome-wide association study of alcohol dependence in male Han Chinese and cross-ethnic polygenic risk score comparison. Translational Psychiatry 2019, 9: 249. PMID: 31591379, PMCID: PMC6779867, DOI: 10.1038/s41398-019-0586-3.Peer-Reviewed Original ResearchAdultAlcohol DehydrogenaseAlcoholismAldehyde Dehydrogenase, MitochondrialAsian PeopleBlack or African AmericanCase-Control StudiesChinaCross-Cultural ComparisonGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansLogistic ModelsMaleMiddle AgedMultifactorial InheritancePolymorphism, Single NucleotideWhite PeopleYoung AdultGenetic associations with suicide attempt severity and genetic overlap with major depression
Levey DF, Polimanti R, Cheng Z, Zhou H, Nuñez YZ, Jain S, He F, Sun X, Ursano RJ, Kessler RC, Smoller JW, Stein MB, Kranzler HR, Gelernter J. Genetic associations with suicide attempt severity and genetic overlap with major depression. Translational Psychiatry 2019, 9: 22. PMID: 30655502, PMCID: PMC6336846, DOI: 10.1038/s41398-018-0340-2.Peer-Reviewed Original ResearchConceptsGWS associationsGenome-wide significant signalsCircadian clock regulationWide association studyGenetic overlapCatabolism of tyrosineClock regulationFirst GWASSignificant genetic overlapDiscovery GWASChromosome 12Large GWASMolecular mechanismsAssociation studiesChromosome 15Chromosome 18Genetic influencesDiscovery sampleGenetic associationSuicide attempt severityReplication analysisGWASAnaerobic energy productionGenetic risk factorsPolygenic risk scores
2018
GWAS and network analysis of co‐occurring nicotine and alcohol dependence identifies significantly associated alleles and network
Xiang B, Yang B, Zhou H, Kranzler H, Gelernter J. GWAS and network analysis of co‐occurring nicotine and alcohol dependence identifies significantly associated alleles and network. American Journal Of Medical Genetics Part B Neuropsychiatric Genetics 2018, 180: 3-11. PMID: 30488612, PMCID: PMC6918694, DOI: 10.1002/ajmg.b.32692.Peer-Reviewed Original ResearchMeSH KeywordsAdultAlcoholismAllelesBlack or African AmericanComorbidityEthanolFemaleG(M2) Activator ProteinGene FrequencyGene Regulatory NetworksGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMaleMiddle AgedNicotinePolymorphism, Single NucleotideProtein Interaction MapsRisk FactorsTobacco Use DisorderWhite PeopleConceptsGene subnetworksProtein-protein interaction (PPI) network analysisGenome-wide significant variantsInteraction network analysisGene-set analysisFunctional enrichment analysisSignificant SNPsQuantitative lociNerve growth factor pathwayGene enrichmentEnrichment analysisNetwork analysisGenetic traitsGrowth factor pathwaysRisk genesSignificant variantsGenesStudy of AddictionSNPsFactor pathwayGM2AAmphetamine addictionGenetic riskGWASSubnetworksGenome‐wide association study of cognitive flexibility assessed by the Wisconsin Card Sorting Test
Zhang H, Zhou H, Lencz T, Farrer LA, Kranzler HR, Gelernter J. Genome‐wide association study of cognitive flexibility assessed by the Wisconsin Card Sorting Test. American Journal Of Medical Genetics Part B Neuropsychiatric Genetics 2018, 177: 511-519. PMID: 30134085, PMCID: PMC6110090, DOI: 10.1002/ajmg.b.32642.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesSingle nucleotide polymorphismsAssociation studiesGenome-wide significant associationUbiquitin-specific peptidase 9Top single nucleotide polymorphismsComplex trait analysisEnriched gene setsPolygenic risk score analysisCommon single nucleotide polymorphismsGWS associationsSame effect directionGene setsPopulation variationProtein degradationNongenetic factorsTrait analysisChromosome 15Genetic correlationsRisk score analysisNucleotide polymorphismsEffect directionEuropean-American subjectsGenetic factorsBrain developmentGenomewide Association Study of Alcohol Dependence and Related Traits in a Thai Population
Gelernter J, Zhou H, Nuñez YZ, Mutirangura A, Malison RT, Kalayasiri R. Genomewide Association Study of Alcohol Dependence and Related Traits in a Thai Population. Alcohol Clinical And Experimental Research 2018, 42: 861-868. PMID: 29460428, PMCID: PMC5916336, DOI: 10.1111/acer.13614.Peer-Reviewed Original ResearchConceptsGenomewide association studiesAssociation studiesRisk genesAldehyde dehydrogenase 2Prior biological informationAfrican ancestry populationsRelated traitsSame geneBiological informationAlcohol dehydrogenasesSignificant pleiotropyDehydrogenase BGenesFunctional variantsPsychiatric traitsGenomewide significant associationPleiotropy analysisTraitsAncestry populationsFirst genomewide association studyPleiotropyDehydrogenase 2Null variants