2023
Multi-ancestry genome-wide association study of cannabis use disorder yields insight into disease biology and public health implications
Levey D, Galimberti M, Deak J, Wendt F, Bhattacharya A, Koller D, Harrington K, Quaden R, Johnson E, Gupta P, Biradar M, Lam M, Cooke M, Rajagopal V, Empke S, Zhou H, Nunez Y, Kranzler H, Edenberg H, Agrawal A, Smoller J, Lencz T, Hougaard D, Børglum A, Demontis D, Gaziano J, Gandal M, Polimanti R, Stein M, Gelernter J. Multi-ancestry genome-wide association study of cannabis use disorder yields insight into disease biology and public health implications. Nature Genetics 2023, 55: 2094-2103. PMID: 37985822, PMCID: PMC10703690, DOI: 10.1038/s41588-023-01563-z.Peer-Reviewed Original ResearchMeSH KeywordsGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMarijuana AbusePolymorphism, Single NucleotidePublic HealthRacial GroupsVeteransConceptsSingle nucleotide polymorphism-based heritabilityMulti-ancestry genome-wide association studyAssociation studiesMillion Veteran ProgramGenome-wide association studiesWide significant lociWide association studySignificant lociReference panelSmall populationDisease biologyAncestryAmerican ancestryHeritabilityVeteran ProgramNumerous medical comorbiditiesLung cancer riskRelationship analysisLociBiologyPublic health implicationsEast AsiansPublic health consequencesMedical comorbiditiesCigarette smoking
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 ResearchMeSH KeywordsAlcoholismBlack PeopleFurinGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansOpioid-Related DisordersPhenotypePolymorphism, Single NucleotideWhite PeopleConceptsGenome-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 ResearchMeSH KeywordsAlcohol DehydrogenaseAlcohol DrinkingAlcoholismAldehyde Dehydrogenase, MitochondrialGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansPolymorphism, Single NucleotideConceptsAlcohol 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
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 ResearchMeSH KeywordsDepressive Disorder, MajorFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMaleVeteransConceptsTranscriptome-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
2019
Genome‐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
Genomewide 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 dependenceGenome-wide association study of therapeutic opioid dosing identifies a novel locus upstream of OPRM1
Smith AH, Jensen KP, Li J, Nunez Y, Farrer LA, Hakonarson H, Cook-Sather SD, Kranzler HR, Gelernter J. Genome-wide association study of therapeutic opioid dosing identifies a novel locus upstream of OPRM1. Molecular Psychiatry 2017, 22: 346-352. PMID: 28115739, PMCID: PMC5407902, DOI: 10.1038/mp.2016.257.Peer-Reviewed Original ResearchMeSH KeywordsAdultAllelesAnalgesics, OpioidBlack or African AmericanDose-Response Relationship, DrugFemaleGene FrequencyGenetic Predisposition to DiseaseGenome-Wide Association StudyGenotypeHumansMaleMethadoneMiddle AgedMorphineOpioid-Related DisordersPainPolymorphism, Single NucleotideReceptors, Opioid, muUnited StatesWhite PeopleConceptsMethadone doseOD subjectsOpioid dependenceSignificant associationDaily methadone doseMethadone maintenance doseOpioid analgesic doseDose of morphineHigher methadone doseDifferent clinical settingsΜ-opioid receptorAnalgesic doseMaintenance doseOral methadoneEffective analgesicSurgical painOpioid sensitivityPrecision pharmacotherapySelective agonistGenome-wide association studiesAA childrenClinical settingDoseMinor alleleOPRM1