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 ResearchConceptsGenome-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 riskNCOA6GeneticsHeritabilityPathwayFemalesEpigenome-wide association study of posttraumatic stress disorder identifies novel loci in U.S. military veterans
Montalvo-Ortiz JL, Gelernter J, Cheng Z, Girgenti MJ, Xu K, Zhang X, Gopalan S, Zhou H, Duman RS, Southwick SM, Krystal JH, Pietrzak R. Epigenome-wide association study of posttraumatic stress disorder identifies novel loci in U.S. military veterans. Translational Psychiatry 2022, 12: 65. PMID: 35177594, PMCID: PMC8854688, DOI: 10.1038/s41398-022-01822-3.Peer-Reviewed Original ResearchConceptsEpigenome-wide association studiesAssociation studiesTranscription regulationCpG sitesGenome-wide association studiesCell type proportionsPosttraumatic stress disorderPotential epigenetic biomarkersSignificant CpG sitesEpigenetic mechanismsDNA methylationNovel lociCell signalingEpigenetic biomarkersMethylation analysisAxonal guidanceNovel molecular biomarkersEPIC BeadChipLifetime posttraumatic stress disorderMilitary veteransPostmortem brain tissueMedial orbitofrontal cortexMolecular biomarkersRegulationU.S. military veterans
2021
Psychosocial moderators of polygenic risk for suicidal ideation: Results from a 7-year population-based, prospective cohort study of U.S. veterans
Na PJ, De Angelis F, Nichter B, Wendt FR, Krystal JH, Southwick SM, Levey DF, Gelernter J, Polimanti R, Pietrzak RH. Psychosocial moderators of polygenic risk for suicidal ideation: Results from a 7-year population-based, prospective cohort study of U.S. veterans. Molecular Psychiatry 2021, 27: 1068-1074. PMID: 34725455, DOI: 10.1038/s41380-021-01352-2.Peer-Reviewed Original ResearchConceptsNew-onset suicidal ideationChronic suicidal ideationPolygenic risk scoresSuicidal ideationProspective cohort studyPolygenic riskRisk of SIHigher baseline levelsHigh polygenic riskModifiable psychosocial factorsSocial supportDispositional optimismCohort studyProspective cohortUS veteransSymptomatic courseRisk scorePsychosocial factorsGenome-wide association studiesBaseline levelsU.S. veteransSuicidal thoughtsPsychosocial moderatorsStudy periodLarge genome-wide association studies
2020
Transcriptomic organization of the human brain in post-traumatic stress disorder
Girgenti MJ, Wang J, Ji D, Cruz DA, Stein M, Gelernter J, Young K, Huber B, Williamson D, Friedman M, Krystal J, Zhao H, Duman R. Transcriptomic organization of the human brain in post-traumatic stress disorder. Nature Neuroscience 2020, 24: 24-33. PMID: 33349712, DOI: 10.1038/s41593-020-00748-7.Peer-Reviewed Original ResearchMeSH KeywordsAdultAutopsyBrain ChemistryCohort StudiesDepressive Disorder, MajorFemaleGene Expression RegulationGene Regulatory NetworksGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansInterneuronsMaleMiddle AgedNerve Tissue ProteinsSex CharacteristicsStress Disorders, Post-TraumaticTranscriptomeYoung AdultConceptsGenome-wide association studiesSignificant gene networksDifferential gene expressionSystems-level evidenceSignificant genetic liabilityMajor depressive disorder cohortGene networksTranscriptomic organizationTranscriptomic landscapeDownregulated setsGenomic networksGene expressionAssociation studiesMolecular determinantsExtensive remodelingGenotype dataSexual dimorphismSignificant divergenceMolecular profileNetwork analysisELFN1TranscriptsDimorphismPostmortem tissueDivergence
2018
Genome-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
2015
Gene-based and pathway-based genome-wide association study of alcohol dependence
Lingjun Z, ZHANG CK, SAYWARD FG, CHEUNG KH, Kesheng W, KRYSTAL JH, Hongyu Z, Xingguang L. Gene-based and pathway-based genome-wide association study of alcohol dependence. General Psychiatry 2015, 27: 111-118. PMID: 26120261, PMCID: PMC4466852, DOI: 10.11919/j.issn.1002-0829.215031.Peer-Reviewed Original ResearchGenome-wide association studiesRisk genesAssociation studiesBiological signaling processesPXN geneGene pathwaysSignaling processesGlycan degradationInteraction pathwayGenetic markersTransporter pathwaysGenesDiscovery samplePathwayReplication sampleAfrican American casesRisk pathwaysMultiple testingBonferroni correctionNew evidence
2013
NKAIN1–SERINC2 is a functional, replicable and genome-wide significant risk gene region specific for alcohol dependence in subjects of European descent
Zuo L, Wang K, Zhang XY, Krystal JH, Li CS, Zhang F, Zhang H, Luo X. NKAIN1–SERINC2 is a functional, replicable and genome-wide significant risk gene region specific for alcohol dependence in subjects of European descent. Drug And Alcohol Dependence 2013, 129: 254-264. PMID: 23455491, PMCID: PMC3628730, DOI: 10.1016/j.drugalcdep.2013.02.006.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesExpression quantitative loci (eQTL) analysisGene regionMetabolic pathwaysQuantitative loci analysisSNP-expression associationsCis-acting regulatory effectsDiscovery sampleSNP-disease associationsNumerous genesReplication sampleLocus analysisAssociation studiesAssociation analysisRisk SNPsTranscript expressionSNPsRegulatory effectsGenesPathwayEuropean descentExpression
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 cases
2011
Erratum: Genome-Wide Association Study of Alcohol Dependence Implicates KIAA0040 on Chromosome 1q
Zuo L, Gelernter J, Zhang C, Zhao H, Lu L, Kranzler H, Malison R, Li C, Wang F, Zhang X, Deng H, Krystal J, Zhang F, Luo X. Erratum: Genome-Wide Association Study of Alcohol Dependence Implicates KIAA0040 on Chromosome 1q. Neuropsychopharmacology 2011, 37: 581-582. PMCID: PMC3242324, DOI: 10.1038/npp.2011.271.Peer-Reviewed Original ResearchGenome-wide association studiesAssociation studiesGenome-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