2023
Multi-ancestry study of the genetics of problematic alcohol use in over 1 million individuals
Zhou H, Kember R, Deak J, Xu H, Toikumo S, Yuan K, Lind P, Farajzadeh L, Wang L, Hatoum A, Johnson J, Lee H, Mallard T, Xu J, Johnston K, Johnson E, Nielsen T, Galimberti M, Dao C, Levey D, Overstreet C, Byrne E, Gillespie N, Gordon S, Hickie I, Whitfield J, Xu K, Zhao H, Huckins L, Davis L, Sanchez-Roige S, Madden P, Heath A, Medland S, Martin N, Ge T, Smoller J, Hougaard D, Børglum A, Demontis D, Krystal J, Gaziano J, Edenberg H, Agrawal A, Justice A, Stein M, Kranzler H, Gelernter J. Multi-ancestry study of the genetics of problematic alcohol use in over 1 million individuals. Nature Medicine 2023, 29: 3184-3192. PMID: 38062264, PMCID: PMC10719093, DOI: 10.1038/s41591-023-02653-5.Peer-Reviewed Original ResearchAlcoholismGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansPhenotypePolymorphism, Single NucleotideRacial Groups
2022
Sex-Specific Genetic and Transcriptomic Liability to Neuroticism
Wendt FR, Pathak GA, Singh K, Stein MB, Koenen KC, Krystal JH, Gelernter J, Davis LK, Polimanti R. Sex-Specific Genetic and Transcriptomic Liability to Neuroticism. Biological Psychiatry 2022, 93: 243-252. PMID: 36244801, PMCID: PMC10508260, DOI: 10.1016/j.biopsych.2022.07.019.Peer-Reviewed Original ResearchMeSH KeywordsFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHSP27 Heat-Shock ProteinsHumansMaleMental DisordersNeuroticismPhenotypePolymorphism, Single NucleotideTranscription FactorsTranscriptomeConceptsGenome-wide association studiesTranscriptomic profilesAssociation studiesSingle nucleotide polymorphism heritabilityGene expression variationGenome-wide significanceSex-specific geneticChromosomal variationTranscriptomic changesRisk lociExpression variationBiological processesMolecular pathwaysLociPolygenic associationSex-specific effectsGenetic correlatesPolygenic scoresUK BiobankGenetic riskNCOA6GeneticsHeritabilityPathwayFemales
2020
Systematic review and meta‐analysis of the moderating effect of rs1799971 in OPRM1, the mu‐opioid receptor gene, on response to naltrexone treatment of alcohol use disorder
Hartwell EE, Feinn R, Morris PE, Gelernter J, Krystal J, Arias AJ, Hoffman M, Petrakis I, Gueorguieva R, Schacht JP, Oslin D, Anton RF, Kranzler HR. Systematic review and meta‐analysis of the moderating effect of rs1799971 in OPRM1, the mu‐opioid receptor gene, on response to naltrexone treatment of alcohol use disorder. Addiction 2020, 115: 1426-1437. PMID: 31961981, PMCID: PMC7340566, DOI: 10.1111/add.14975.Peer-Reviewed Original ResearchMeSH KeywordsAdultAlcohol DrinkingAlcoholismAllelesFemaleGenotypeHumansMaleNaltrexoneNarcotic AntagonistsPolymorphism, Single NucleotideRandomized Controlled Trials as TopicReceptors, Opioid, muRecurrenceConceptsAsn40Asp single-nucleotide polymorphismRandomized clinical trialsAlcohol use disorderNaltrexone treatmentMu-opioid receptor geneUse disordersSingle nucleotide polymorphismsPlacebo-controlled randomized clinical trialsSystematic reviewPublication biasOpioid receptor antagonist naltrexoneWide inter-individual variabilityHeavy drinkingRisk of biasNaltrexone treatment responseReceptor geneRandom-effects modelAlcohol consumption outcomesAntagonist naltrexoneInter-individual variabilityStudy criteriaClinical trialsNucleotide polymorphismsTreatment responseMinor allele
2018
BDNF Val66Met polymorphism and posttraumatic stress symptoms in U.S. military veterans: Protective effect of physical exercise
Pitts BL, Whealin JM, Harpaz-Rotem I, Duman RS, Krystal JH, Southwick SM, Pietrzak RH. BDNF Val66Met polymorphism and posttraumatic stress symptoms in U.S. military veterans: Protective effect of physical exercise. Psychoneuroendocrinology 2018, 100: 198-202. PMID: 30388593, DOI: 10.1016/j.psyneuen.2018.10.011.Peer-Reviewed Original ResearchMeSH KeywordsAgedAmino Acid SubstitutionBrain-Derived Neurotrophic FactorCase-Control StudiesExerciseFemaleHumansMaleMethionineMiddle AgedMilitary PersonnelPolymorphism, Single NucleotideProtective FactorsResilience, PsychologicalSeverity of Illness IndexStress Disorders, Post-TraumaticUnited StatesValineVeteransConceptsMet allele carriersBDNF Val66Met polymorphismAllele carriersVal66Met polymorphismPhysical exerciseGreater severityPTSD symptomsU.S. military veteransTrauma burdenBrain-derived neurotrophic factor (BDNF) Val66Met polymorphismPast-month PTSD symptomsNeurotrophic factor Val66Met polymorphismMilitary veteransLifetime trauma burdenHigh trauma burdenVal/ValAdrenal (HPA) axis reactivityPosttraumatic stress disorder (PTSD) symptomsBDNF releaseCurrent PTSD symptomsProtective effectRe-experiencing symptomsAxis reactivityPosttraumatic stress symptomsSymptomsGenome-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 transmission
2017
GRIK1 and GABRA2 Variants Have Distinct Effects on the Dose‐Related Subjective Response to Intravenous Alcohol in Healthy Social Drinkers
Yang B, Arias AJ, Feinn R, Krystal JH, Gelernter J, Petrakis IL. GRIK1 and GABRA2 Variants Have Distinct Effects on the Dose‐Related Subjective Response to Intravenous Alcohol in Healthy Social Drinkers. Alcohol Clinical And Experimental Research 2017, 41: 2025-2032. PMID: 29131352, PMCID: PMC5764175, DOI: 10.1111/acer.13516.Peer-Reviewed Original ResearchAssociation Between Functional Polymorphism in Neuropeptide Y Gene Promoter rs16147 and Resilience to Traumatic Stress in US Military Veterans.
Watkins LE, Han S, Krystal JH, Southwick SM, Gelernter J, Pietrzak RH. Association Between Functional Polymorphism in Neuropeptide Y Gene Promoter rs16147 and Resilience to Traumatic Stress in US Military Veterans. The Journal Of Clinical Psychiatry 2017, 78: e1058-e1059. PMID: 29099554, DOI: 10.4088/jcp.17l11646.Peer-Reviewed Original ResearchAttachment style moderates effects of FKBP5 polymorphisms and childhood abuse on post-traumatic stress symptoms: Results from the National Health and Resilience in Veterans Study
Tamman AJF, Sippel LM, Han S, Neria Y, Krystal JH, Southwick SM, Gelernter J, Pietrzak RH. Attachment style moderates effects of FKBP5 polymorphisms and childhood abuse on post-traumatic stress symptoms: Results from the National Health and Resilience in Veterans Study. The World Journal Of Biological Psychiatry 2017, 20: 289-300. PMID: 28891785, DOI: 10.1080/15622975.2017.1376114.Peer-Reviewed Original ResearchOxytocin receptor gene polymorphisms, attachment, and PTSD: Results from the National Health and Resilience in Veterans Study
Sippel LM, Han S, Watkins LE, Harpaz-Rotem I, Southwick SM, Krystal JH, Olff M, Sherva R, Farrer LA, Kranzler HR, Gelernter J, Pietrzak RH. Oxytocin receptor gene polymorphisms, attachment, and PTSD: Results from the National Health and Resilience in Veterans Study. Journal Of Psychiatric Research 2017, 94: 139-147. PMID: 28715704, PMCID: PMC5605420, DOI: 10.1016/j.jpsychires.2017.07.008.Peer-Reviewed Original Research
2016
Implication of NOTCH1 gene in susceptibility to anxiety and depression among sexual abuse victims
Steine IM, Zayats T, Stansberg C, Pallesen S, Mrdalj J, Håvik B, Soulé J, Haavik J, Milde AM, Skrede S, Murison R, Krystal J, Grønli J. Implication of NOTCH1 gene in susceptibility to anxiety and depression among sexual abuse victims. Translational Psychiatry 2016, 6: e977-e977. PMID: 27959334, PMCID: PMC5290341, DOI: 10.1038/tp.2016.248.Peer-Reviewed Original ResearchMeSH KeywordsAllelesAnimalsAnxiety DisordersBrainDepressive DisorderDisease Models, AnimalFemaleGene ExpressionGenetic Predisposition to DiseaseHumansLife Change EventsMaleNeurodevelopmental DisordersPolymorphism, Single NucleotideRats, WistarReceptor, Notch1Sex OffensesTranslational Research, BiomedicalConceptsSingle nucleotide polymorphismsDifferent early-life conditionsGene expressionEarly-life conditionsBrain gene expressionGenetic association studiesCandidate genesAssociation studiesNeural developmentDifferential expressionTag single nucleotide polymorphismsBrain of rodentsGenesHuman samplesFalse discovery rateNotch1 geneSymptoms of anxietyExpressionSignificance analysisDiscovery ratePotential importanceEarly life stressMeans of correspondencePotential relevancePlk5FKBP5 polymorphisms, childhood abuse, and PTSD symptoms: Results from the National Health and Resilience in Veterans Study
Watkins LE, Han S, Harpaz-Rotem I, Mota NP, Southwick SM, Krystal JH, Gelernter J, Pietrzak RH. FKBP5 polymorphisms, childhood abuse, and PTSD symptoms: Results from the National Health and Resilience in Veterans Study. Psychoneuroendocrinology 2016, 69: 98-105. PMID: 27078785, DOI: 10.1016/j.psyneuen.2016.04.001.Peer-Reviewed Original ResearchAdultAllelesChildChild AbuseGene-Environment InteractionGenetic Predisposition to DiseaseGenotypeHumansHypothalamo-Hypophyseal SystemLinkage DisequilibriumMalePituitary-Adrenal SystemPolymorphism, Single NucleotideRisk FactorsStress Disorders, Post-TraumaticSubstance-Related DisordersTacrolimus Binding ProteinsVeterans
2015
A New Genomewide Association Meta‐Analysis of Alcohol Dependence
Zuo L, Tan Y, Zhang X, Wang X, Krystal J, Tabakoff B, Zhong C, Luo X. A New Genomewide Association Meta‐Analysis of Alcohol Dependence. Alcohol Clinical And Experimental Research 2015, 39: 1388-1395. PMID: 26173551, PMCID: PMC5587504, DOI: 10.1111/acer.12786.Peer-Reviewed Original ResearchMeSH KeywordsAlcoholismAnimalsAustraliaCohort StudiesEuropeGenome-Wide Association StudyHumansMicePolymorphism, Single NucleotideRatsRisk FactorsWhite PeopleConceptsAfrican American cohortAmerican cohortAlcohol dependenceSingle nucleotide polymorphismsAustralian cohortRisk genesEuropean American cohortRisk single nucleotide polymorphismsRat brainIndependent cohortMeta-AnalysisCohortMouse brainRisk variantsP-valueRNA expression analysisGenomewide association studiesBrainHuman tissuesNucleotide polymorphismsAssociation studiesGenomewide association analysisSignificant association between rare IPO11‐HTR1A variants and attention deficit hyperactivity disorder in Caucasians
Zuo L, Saba L, Lin X, Tan Y, Wang K, Krystal JH, Tabakoff B, Luo X. Significant association between rare IPO11‐HTR1A variants and attention deficit hyperactivity disorder in Caucasians. American Journal Of Medical Genetics Part B Neuropsychiatric Genetics 2015, 168: 544-556. PMID: 26079129, PMCID: PMC4851708, DOI: 10.1002/ajmg.b.32329.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAttention Deficit Disorder with HyperactivityBeta KaryopherinsBlack or African AmericanFemaleGene FrequencyGenetic Predisposition to DiseaseGenetic VariationHumansMaleMiddle AgedPolymorphism, Single NucleotideQuantitative Trait LociReceptor, Serotonin, 5-HT1ARisk FactorsWhite PeopleConceptsAttention deficit hyperactivity disorderDeficit hyperactivity disorderNeuropsychiatric disordersRare variantsHyperactivity disorderDifferent neuropsychiatric disordersRNA expression changesIndependent cohortSignificant associationSignificant regulatory effectDisordersCaucasiansEuropean descentRegulatory effectsHuman brainDiseaseAssociationCis-eQTL analysisIPO11African descentExpression changesSubjectsCohortFalse discovery rateVariants
2013
Sex chromosome-wide association analysis suggested male-specific risk genes for alcohol dependence
Zuo L, Wang K, Zhang X, Pan X, Wang G, Krystal JH, Zhang H, Luo X. Sex chromosome-wide association analysis suggested male-specific risk genes for alcohol dependence. Psychiatric Genetics 2013, 23: 233-238. PMID: 23907288, PMCID: PMC3941913, DOI: 10.1097/ypg.0b013e328364b8c7.Peer-Reviewed Original ResearchRare SERINC2 variants are specific for alcohol dependence in individuals of European descent
Zuo L, Wang KS, Zhang XY, Li CS, Zhang F, Wang X, Chen W, Gao G, Zhang H, Krystal JH, Luo X. Rare SERINC2 variants are specific for alcohol dependence in individuals of European descent. Pharmacogenetics And Genomics 2013, 23: 395-402. PMID: 23778322, PMCID: PMC4287355, DOI: 10.1097/fpc.0b013e328362f9f2.Peer-Reviewed Original ResearchExome-wide association study of replicable nonsynonymous variants conferring risk for alcohol dependence.
Zuo L, Saba L, Wang K, Zhang X, Krystal JH, Tabakoff B, Luo X. Exome-wide association study of replicable nonsynonymous variants conferring risk for alcohol dependence. Journal Of Studies On Alcohol And Drugs 2013, 74: 622-5. PMID: 23739027, PMCID: PMC3711352, DOI: 10.15288/jsad.2013.74.622.Peer-Reviewed Original ResearchConceptsApolipoprotein E receptor 2Risk genesNonsynonymous variantsRNA expression analysisExome-wide association studyE receptor 2Expression analysisAssociation studiesGenesWhole exomeProtein 2RNA expressionNsSNPReplicable associationsAlcohol dependenceNonhuman speciesEuropean American sampleReceptor 2UbiquitinVariantsMultiple testingSpeciesExomeBioinformaticsUBAP2Association between common alcohol dehydrogenase gene (ADH) variants and schizophrenia and autism
Zuo L, Wang K, Zhang XY, Pan X, Wang G, Tan Y, Zhong C, Krystal JH, State M, Zhang H, Luo X. Association between common alcohol dehydrogenase gene (ADH) variants and schizophrenia and autism. Human Genetics 2013, 132: 735-743. PMID: 23468174, PMCID: PMC3683370, DOI: 10.1007/s00439-013-1277-4.Peer-Reviewed Original Research
2012
Genome‐Wide Significant Association Signals in IPO11‐HTR1A Region Specific for Alcohol and Nicotine Codependence
Zuo L, Zhang X, Wang F, Li C, Lu L, Ye L, Zhang H, Krystal JH, Deng H, Luo X. Genome‐Wide Significant Association Signals in IPO11‐HTR1A Region Specific for Alcohol and Nicotine Codependence. Alcohol Clinical And Experimental Research 2012, 37: 730-739. PMID: 23216389, PMCID: PMC3610804, DOI: 10.1111/acer.12032.Peer-Reviewed Original ResearchMeSH KeywordsAdultAlcoholismBeta KaryopherinsBlack or African AmericanCase-Control StudiesChromosomes, Human, Pair 5FemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyGenotypeHumansMaleMiddle AgedPolymorphism, Single NucleotideQuantitative Trait LociReceptor, Serotonin, 5-HT1ATobacco Use DisorderWhite PeopleConceptsGenome-wide significance levelSingle nucleotide polymorphismsReplication cohortDiscovery cohortAlcohol dependenceExpression quantitative loci (eQTL) analysisPeripheral blood mononuclear cell samplesNeuropsychiatric disordersWide significant association signalsMononuclear cell samplesGenome-wide association studiesQuantitative loci analysisGene-disease association analysisCis-eQTL analysisTop single nucleotide polymorphismsCis-acting regulatory effectsSignificant association signalsBrain tissue samplesAmerican controlsEuropean American controlsRisk single nucleotide polymorphismsAfrican-American controlsSevere subtypeGenomic regionsAfrican American casesGenome‐wide search for replicable risk gene regions in alcohol and nicotine co‐dependence
Zuo L, Zhang F, Zhang H, Zhang X, Wang F, Li C, Lu L, Hong J, Lu L, Krystal J, Deng H, Luo X. Genome‐wide search for replicable risk gene regions in alcohol and nicotine co‐dependence. American Journal Of Medical Genetics Part B Neuropsychiatric Genetics 2012, 159B: 437-444. PMID: 22488850, PMCID: PMC3405545, DOI: 10.1002/ajmg.b.32047.Peer-Reviewed Original ResearchConceptsChromosome 3Genome-wide false discovery rateGene regionFalse discovery rateGenome-wide association analysisExpression quantitative trait loci (eQTL) analysisQuantitative trait locus (QTL) analysisRisk SNPsTranscript expressionGenome-wide association strategyGenome-wide searchCombined P valueSNP-disease associationsAssociation peakGenomic regionsEQTL analysisEuropean American casesCausal lociLocus analysisGene expressionAssociation analysisGenesSNPsRegulatory effectsDiscovery rate
2011
Genome-Wide Association Study of Alcohol Dependence Implicates KIAA0040 on Chromosome 1q
Zuo L, Gelernter J, Zhang CK, Zhao H, Lu L, Kranzler HR, Malison RT, Li CS, Wang F, Zhang XY, Deng HW, Krystal JH, Zhang F, Luo X. Genome-Wide Association Study of Alcohol Dependence Implicates KIAA0040 on Chromosome 1q. Neuropsychopharmacology 2011, 37: 557-566. PMID: 21956439, PMCID: PMC3242317, DOI: 10.1038/npp.2011.229.Peer-Reviewed Original ResearchConceptsSignificant risk genesHapMap populationsGenome-wide association analysisExpression quantitative trait loci (eQTL) analysisGenome-wide association study data setsQuantitative trait locus (QTL) analysisAssociation analysisMetabolic pathwaysRisk genesGenome-wide association studiesSNP-expression associationsCis-acting regulatory effectsExtracellular matrix proteinsGene expression levelsNumerous genesSignificant SNPsCausal variantsKIAA0040Risk lociRisk of ADLocus analysisAssociation studiesMatrix proteinsRisk SNPsCell migration