Featured Publications
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 AmericansConsortiumGenome-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 dependence
2024
Genome-wide association study of the common retinal disorder epiretinal membrane: Significant risk loci in each of three American populations
Gelernter J, Levey D, Galimberti M, Harrington K, Zhou H, Adhikari K, Gupta P, Program V, Gaziano J, Eliott D, Stein M. Genome-wide association study of the common retinal disorder epiretinal membrane: Significant risk loci in each of three American populations. Cell Genomics 2024, 4: 100582. PMID: 38870908, PMCID: PMC11228954, DOI: 10.1016/j.xgen.2024.100582.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesMillion Veteran ProgramRisk lociAssociation studiesTrans-ancestry meta-analysisSignificant risk lociPathway enrichment analysisEpiretinal membraneTrans-ancestryGenome-wideMultiple traitsGenetic associationEnrichment analysisGene expressionEuropean AmericansLoss of visual acuityVeteran ProgramGenetic correlationsLociBiological mechanismsAmerican populationVisual acuityRetinal conditionsControl individualsRetinal surface
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 AdultGenome‐wide scan identifies opioid overdose risk locus close to MCOLN1
Cheng Z, Yang B, Zhou H, Nunez Y, Kranzler HR, Gelernter J. Genome‐wide scan identifies opioid overdose risk locus close to MCOLN1. Addiction Biology 2019, 25: e12811. PMID: 31362332, PMCID: PMC7485539, DOI: 10.1111/adb.12811.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesMucolipin-1Expression profilesGenome-wide significant signalsAssociation studiesPost-GWAS analysisWide association studyDrug repositioning analysisCation channel activityFunctional categoriesConnectivity Map databaseDrug targetsRisk genesGenesChannel activityPatatin-like phospholipaseNetwork analysisPNPLA6Significant signalEuropean AmericansGenetic 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 developmentGenome-wide Association Study Identifies a Regulatory Variant of RGMA Associated With Opioid Dependence in European Americans
Cheng Z, Zhou H, Sherva R, Farrer LA, Kranzler HR, Gelernter J. Genome-wide Association Study Identifies a Regulatory Variant of RGMA Associated With Opioid Dependence in European Americans. Biological Psychiatry 2018, 84: 762-770. PMID: 29478698, PMCID: PMC6041180, DOI: 10.1016/j.biopsych.2017.12.016.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesAssociation studiesHomologous mouse geneMouse geneAxon guidance proteinRegulatory variantsCoexpression analysisOpioid dependenceTranscript variantsGenetic studiesChromosome 15Guidance proteinsRNA expressionNominal significanceMessenger RNA expressionGenesRepulsive guidance molecule AHigh expressionRGMaRisk allelesChronic morphine injectionDSM-IV diagnosisExpressionNew leadsMorphine injection