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 directionsGenesLoci
2022
Genome-wide association study in individuals of European and African ancestry and multi-trait analysis of opioid use disorder identifies 19 independent genome-wide significant risk loci
Deak JD, Zhou H, Galimberti M, Levey DF, Wendt FR, Sanchez-Roige S, Hatoum AS, Johnson EC, Nunez YZ, Demontis D, Børglum AD, Rajagopal VM, Jennings MV, Kember RL, Justice AC, Edenberg HJ, Agrawal A, Polimanti R, Kranzler HR, Gelernter J. Genome-wide association study in individuals of European and African ancestry and multi-trait analysis of opioid use disorder identifies 19 independent genome-wide significant risk loci. Molecular Psychiatry 2022, 27: 3970-3979. PMID: 35879402, PMCID: PMC9718667, DOI: 10.1038/s41380-022-01709-1.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesGenome-wide significant risk lociAssociation studiesVariant associationsLarge-scale genome-wide association studiesGenetic correlationsSignificant risk lociPsychiatric Genomics ConsortiumMulti-trait analysisPolygenic risk score analysisSingle-variant associationsGWS lociGenetic architectureIndividuals of EuropeanGWS associationsRisk lociGene regionGenomics ConsortiumMillion Veteran ProgramSusceptibility lociAfrican ancestryLociRisk score analysisGenetic informativenessSNPs oneGenome-wide meta-analysis of alcohol use disorder in East Asians
Zhou H, Kalayasiri R, Sun Y, Nuñez YZ, Deng HW, Chen XD, Justice AC, Kranzler HR, Chang S, Lu L, Shi J, Sanichwankul K, Mutirangura A, Malison RT, Gelernter J. Genome-wide meta-analysis of alcohol use disorder in East Asians. Neuropsychopharmacology 2022, 47: 1791-1797. PMID: 35094024, PMCID: PMC9372033, DOI: 10.1038/s41386-022-01265-w.Peer-Reviewed Original ResearchConceptsAlcohol use disorderAlcohol dependenceUse disordersICD-9-CM diagnosisGenome-wide association studiesEast Asian subjectsElectronic health recordsPack yearsLeading causePolygenic risk scoresThai cohortRisk scoreAlcohol consumptionDSM-IVAsian subjectsCohortMillion Veteran Program sampleHealth recordsLarge genome-wide association studiesEast AsiansOngoing recruitmentRisk genesDisordersRisk lociSubjects
2020
Association of OPRM1 Functional Coding Variant With Opioid Use Disorder
Zhou H, Rentsch CT, Cheng Z, Kember RL, Nunez YZ, Sherva RM, Tate JP, Dao C, Xu K, Polimanti R, Farrer LA, Justice AC, Kranzler HR, Gelernter J. Association of OPRM1 Functional Coding Variant With Opioid Use Disorder. JAMA Psychiatry 2020, 77: 1072-1080. PMID: 32492095, PMCID: PMC7270886, DOI: 10.1001/jamapsychiatry.2020.1206.Peer-Reviewed Original ResearchConceptsOpioid use disorderUse disordersMendelian randomization analysisAfrican American individualsMAIN OUTCOMEFunctional coding variantSignificant associationCausal associationRandomization analysisElectronic health record dataCurrent opioid crisisAmerican individualsHealth record dataCognitive performanceInternational Statistical ClassificationRelated Health ProblemsPotential causal associationAmerican controlsEuropean American controlsAfrican-American controlsCoding variantBuprenorphine treatmentOUD diagnosisTobacco smokingNinth Revision
2019
Genetic 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 scoresGenome‐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 Americans
2018
Translational 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 lociGenomewide 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
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