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 Investigation of Maximum Habitual Alcohol Intake in US Veterans in Relation to Alcohol Consumption Traits and Alcohol Use Disorder
Deak JD, Levey DF, Wendt FR, Zhou H, Galimberti M, Kranzler HR, Gaziano JM, Stein MB, Polimanti R, Gelernter J, Muralidhar S, Moser J, Deen J, Gaziano J, Beckham J, Chang K, Tsao P, Luoh S, Casas J, Churby L, Whitbourne S, Brewer J, Brophy M, Selva L, Shayan S, Cho K, Pyarajan S, DuVall S, Connor T, Argyres D, Aslan M, Stephens B, Concato J, Gelernter J, Gleason T, Huang G, Koenen K, Marx C, Radhakrishnan K, Schork N, Stein M, Zhao H, Kaufman J, Nunez Y, Pietrzak R, Beck D, Cissell S, Crutchfield P, Lance W, Cheung K, Li Y, Sun N, Chen Q, Rajeevan N, Sayward F, Gagnon D, Harrington K, Quaden R, O'Leary T, Ramoni R. Genome-Wide Investigation of Maximum Habitual Alcohol Intake in US Veterans in Relation to Alcohol Consumption Traits and Alcohol Use Disorder. JAMA Network Open 2022, 5: e2238880. PMID: 36301540, PMCID: PMC9614582, DOI: 10.1001/jamanetworkopen.2022.38880.Peer-Reviewed Original ResearchMeSH KeywordsAgedAlcohol DrinkingAlcoholismFemaleGenome-Wide Association StudyHumansMaleVeteransWhite PeopleConceptsGenome-wide association studiesGenome-wide significant lociGenomic structural equation modelingSignificant lociAlcohol traitsAssociation studiesAfrican ancestry participantsGenome-wide investigationAncestry-specific genome-wide association studiesGenetic correlationsPsychiatric traitsLinkage disequilibrium score regressionGenetic associationStrong genetic correlationSingle nucleotide variantsGenetic architectureGenetic association studiesGenetic lociTop associationsNegative rgEuropean ancestry participantsNucleotide variantsFunctional variantsScore regressionTraitsGenome-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 directionsGenesLociEpigenomic Profiles of African-American Transthyretin Val122Ile Carriers Reveals Putatively Dysregulated Amyloid Mechanisms
Pathak GA, Wendt FR, De Lillo A, Nunez YZ, Goswami A, De Angelis F, Fuciarelli M, Kranzler HR, Gelernter J, Polimanti R. Epigenomic Profiles of African-American Transthyretin Val122Ile Carriers Reveals Putatively Dysregulated Amyloid Mechanisms. Circulation Genomic And Precision Medicine 2021, 14: e003011. PMID: 33428857, PMCID: PMC7887108, DOI: 10.1161/circgen.120.003011.Peer-Reviewed Original ResearchAmyloidosisATP Binding Cassette Transporter 1Black or African AmericanDNA MethylationEpigenomicsGene Regulatory NetworksGenome-Wide Association StudyHeart DiseasesHumansKv1.6 Potassium ChannelPhosphoproteinsPolymorphism, Single NucleotidePrealbuminQuantitative Trait LociUbiquitin-Conjugating Enzymes
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 ResearchMeSH KeywordsAgedFemaleGenome-Wide Association StudyHumansMaleMiddle AgedOpioid-Related DisordersReceptors, Opioid, muUnited StatesUnited States Department of Veterans AffairsConceptsOpioid 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
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
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
Genome-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