2023
Profiling neuronal methylome and hydroxymethylome of opioid use disorder in the human orbitofrontal cortex
Rompala G, Nagamatsu S, Martínez-Magaña J, Nuñez-Ríos D, Wang J, Girgenti M, Krystal J, Gelernter J, Hurd Y, Montalvo-Ortiz J. Profiling neuronal methylome and hydroxymethylome of opioid use disorder in the human orbitofrontal cortex. Nature Communications 2023, 14: 4544. PMID: 37507366, PMCID: PMC10382503, DOI: 10.1038/s41467-023-40285-y.Peer-Reviewed Original ResearchConceptsOpioid use disorderMulti-omics findingsGene expression patternsCo-methylation analysisGene expression profilesMulti-omics profilingGene networksDNA methylationNeuronal methylomesDNA hydroxymethylationMethylomic analysisExpression patternsExpression profilesEpigenetic disturbancesUse disordersPsychiatric traitsOrbitofrontal cortexOpioid-related drugsPostmortem orbitofrontal cortexEnvironmental factorsDrug interaction analysisOUD treatmentHuman orbitofrontal cortexOpioid signalingInteraction analysis
2022
Dissecting the epigenomic differences between smoking and nicotine dependence in a veteran cohort
Nagamatsu S, Pietrzak R, Xu K, Krystal J, Gelernter J, Montalvo‐Ortiz J. Dissecting the epigenomic differences between smoking and nicotine dependence in a veteran cohort. Addiction Biology 2022, 28: e13259. PMID: 36577721, DOI: 10.1111/adb.13259.Peer-Reviewed Original ResearchConceptsSmoking statusNicotine dependenceVeteran cohortNon-current smokersSerious public health issueNovel treatment strategiesPublic health issueUS military veteransEpigenome-wide association studiesCurrent smokersTreatment strategiesFagerström TestNicotine addictionSmokingHealth issuesRole of epigeneticsMilitary veteransMethylationEPIC BeadChip arraySmokersContinuous variablesF2RL3 geneCohortBiomarkersBeadChip arrayPrevious findingsPsychosocial Factors Associated With Accelerated GrimAge in Male U.S. Military Veterans
Tamman AJF, Nagamatsu S, Krystal JH, Gelernter J, Montalvo-Ortiz JL, Pietrzak RH. Psychosocial Factors Associated With Accelerated GrimAge in Male U.S. Military Veterans. American Journal Of Geriatric Psychiatry 2022, 31: 97-109. PMID: 36210262, DOI: 10.1016/j.jagp.2022.09.002.Peer-Reviewed Original ResearchConceptsRisk factorsPremature mortalityU.S. veteransPsychosocial variablesNovel epigenetic clockLifetime substance use disorderRisk stratification modelMale U.S. veteransCross-sectional studyU.S. veteran populationWeekly physical exerciseSubstance use disordersMale U.S. military veteransBiological agingU.S. military veteransHealth morbidityModifiable correlatesMortality riskSleep qualityHigh riskGreater oddsUse disordersPhysical exercisePsychosocial factorsVeteran populationEpigenome-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 ResearchMeSH KeywordsDNA MethylationEpigenomeGenome-Wide Association StudyHumansMaleStress Disorders, Post-TraumaticVeteransConceptsEpigenome-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
Epigenomic 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
2019
Epigenome‐Wide DNA Methylation Association Analysis Identified Novel Loci in Peripheral Cells for Alcohol Consumption Among European American Male Veterans
Xu K, Montalvo‐Ortiz J, Zhang X, Southwick SM, Krystal JH, Pietrzak RH, Gelernter J. Epigenome‐Wide DNA Methylation Association Analysis Identified Novel Loci in Peripheral Cells for Alcohol Consumption Among European American Male Veterans. Alcohol Clinical And Experimental Research 2019, 43: 2111-2121. PMID: 31386212, PMCID: PMC9377208, DOI: 10.1111/acer.14168.Peer-Reviewed Original ResearchConceptsEpigenome-wide association studiesDNA methylationCpG sitesSignificant CpG sitesHigh-density methylation arraysNovel DNA methylation sitesNew CpG sitesDNA methylation sitesEpigenome-wide DNA methylationAmino acid transportIndividual CpG sitesGene lengthPeripheral cellsNovel lociDNA sitesKEGG databaseMethylation sitesEnrichment analysisMethylation arraysAssociation studiesAssociation analysisGenesMethylationAcid transportFalse discovery rateGenomewide Study of Epigenetic Biomarkers of Opioid Dependence in European- American Women
Montalvo-Ortiz JL, Cheng Z, Kranzler HR, Zhang H, Gelernter J. Genomewide Study of Epigenetic Biomarkers of Opioid Dependence in European- American Women. Scientific Reports 2019, 9: 4660. PMID: 30874594, PMCID: PMC6420601, DOI: 10.1038/s41598-019-41110-7.Peer-Reviewed Original ResearchConceptsEpigenome-wide association studiesEpigenetic mechanismsAssociation studiesAssociation analysisCpG sitesFirst epigenome-wide association studyGenome-wide association studiesPrevious genome-wide association studyCandidate gene approachChromatin remodelingDNA bindingGene approachGenomewide studiesDNA methylation ageCell survivalEpigenetic biomarkersRisk variantsPopulation stratificationMethylation ageGenesCell projectionsOpioid dependenceNovel peripheral biomarkersEuropean American womenCell proportion
2018
Using DNA methylation to validate an electronic medical record phenotype for smoking
McGinnis KA, Justice AC, Tate JP, Kranzler HR, Tindle HA, Becker WC, Concato J, Gelernter J, Li B, Zhang X, Zhao H, Crothers K, Xu K, Group F. Using DNA methylation to validate an electronic medical record phenotype for smoking. Addiction Biology 2018, 24: 1056-1065. PMID: 30284751, PMCID: PMC6541538, DOI: 10.1111/adb.12670.Peer-Reviewed Original ResearchConceptsVeterans Aging Cohort StudyAging Cohort StudyStrong associationDNA methylation sitesSmoking metricsCohort studyCurrent smokingSmoking statusSpearman correlation coefficientBiomarker cohortBlood samplesSmoking behaviorCriterion standardLogistic regressionSmokingSmoking phenotypesCurve analysisGroup assignmentText notesAssociationDescriptive statisticsPhenotypeCorrelation coefficientGenetic discoveriesPercentAdverse Childhood Experiences, Epigenetic Measures, and Obesity in Youth
Kaufman J, Montalvo-Ortiz JL, Holbrook H, O'Loughlin K, Orr C, Kearney C, Yang BZ, Wang T, Zhao H, Althoff R, Garavan H, Gelernter J, Hudziak J. Adverse Childhood Experiences, Epigenetic Measures, and Obesity in Youth. The Journal Of Pediatrics 2018, 202: 150-156.e3. PMID: 30177354, PMCID: PMC6513669, DOI: 10.1016/j.jpeds.2018.06.051.Peer-Reviewed Original ResearchConceptsBody mass indexAdverse childhood experiencesMass indexIndices of obesityAssessment of obesityChildhood experiencesFuture longitudinal studiesObesity riskHealth burdenPsychiatric outcomesSecond cohortObesityNovel interventionsCohortEarly adversityCross-sectional measuresEpigenetic predictorsLongitudinal studySaliva DNAEpigenetic measuresWhole genome testingDiscovery sampleReplication sampleChildrenRiskMethylation in OTX2 and related genes, maltreatment, and depression in children
Kaufman J, Wymbs NF, Montalvo-Ortiz JL, Orr C, Albaugh MD, Althoff R, O’Loughlin K, Holbrook H, Garavan H, Kearney C, Yang BZ, Zhao H, Peña C, Nestler EJ, Lee RS, Mostofsky S, Gelernter J, Hudziak J. Methylation in OTX2 and related genes, maltreatment, and depression in children. Neuropsychopharmacology 2018, 43: 2204-2211. PMID: 30089883, PMCID: PMC6135753, DOI: 10.1038/s41386-018-0157-y.Peer-Reviewed Original ResearchConceptsMouse modelStress-related depressive disordersResting-state functional connectivity dataResting-state functional MRI dataDepressive-like behaviorEarly life stressSubset of childrenDNA specimensMedial frontal cortexPeripheral markersMeasures of depressionHomeobox 2 geneSubcallosal gyrusFunctional connectivity dataDepressive disorderFrontal cortexChild adversityMultiple molecular toolsFunctional MRI dataFrontal poleLarger studyFunctional connectivitySaliva samplesBilateral regionsUnbiased transcriptomics
2017
Genetic–epigenetic interactions in cis: a major focus in the post-GWAS era
Do C, Shearer A, Suzuki M, Terry MB, Gelernter J, Greally JM, Tycko B. Genetic–epigenetic interactions in cis: a major focus in the post-GWAS era. Genome Biology 2017, 18: 120. PMID: 28629478, PMCID: PMC5477265, DOI: 10.1186/s13059-017-1250-y.Peer-Reviewed Original ResearchConceptsMethylation quantitative trait lociCCCTC-binding factorEpigenome-wide association studiesGenetic-epigenetic interactionsAllele-specific DNA methylationSequence variantsPost-GWAS eraQuantitative trait lociRegulatory sequence variantsGWAS signalsTrait lociDNA methylationTranscription factorsTranscriptional pathwaysAssociation studiesNon-genetic effectsStudy eraMajor focusMethylationLociVariantsCommon diseaseSitesNeuropsychiatric disordersPathwayAlcohol and nicotine codependence-associated DNA methylation changes in promoter regions of addiction-related genes
Xu H, Wang F, Kranzler HR, Gelernter J, Zhang H. Alcohol and nicotine codependence-associated DNA methylation changes in promoter regions of addiction-related genes. Scientific Reports 2017, 7: 41816. PMID: 28165486, PMCID: PMC5292964, DOI: 10.1038/srep41816.Peer-Reviewed Original Research
2016
Review: DNA methylation and alcohol use disorders: Progress and challenges
Zhang H, Gelernter J. Review: DNA methylation and alcohol use disorders: Progress and challenges. American Journal On Addictions 2016, 26: 502-515. PMID: 27759945, PMCID: PMC6003819, DOI: 10.1111/ajad.12465.Peer-Reviewed Original ResearchConceptsDNA methylation changesDNA methylationMethylation changesGenome-wide DNA methylation studyGene expressionPromoter regionGlobal DNA methylation levelsDNA methylation profilesDNA methylation studiesDNA methylation levelsWidespread DNA methylationCandidate gene studiesEpigenetic mechanismsGenetic variationConsequences of AUDMethylation profilesMethylation studiesGene studiesMethylation levelsMethylationAUD subjectsGene-environment interactionsEnvironmental factorsInteractive effectsExpressionDNA co-methylation modules in postmortem prefrontal cortex tissues of European Australians with alcohol use disorders
Wang F, Xu H, Zhao H, Gelernter J, Zhang H. DNA co-methylation modules in postmortem prefrontal cortex tissues of European Australians with alcohol use disorders. Scientific Reports 2016, 6: 19430. PMID: 26763658, PMCID: PMC4725922, DOI: 10.1038/srep19430.Peer-Reviewed Original ResearchConceptsCo-methylation modulesPostmortem prefrontal cortex tissueDNA methylome alterationsCo-methylation analysisDNA methylation alterationsSubstance dependence phenotypesTranscriptional regulationDNA methylomeMethylation alterationsMethylome alterationsBiological processesPostmortem prefrontal cortexExpression relationshipsNeural developmentDifferential expressionPrefrontal cortex tissueGenesDependence phenotypesMultiple testing correctionCpGAUD subjectsFemale pairsCortex tissueMethylomePhenotype
2014
Identification of methylation quantitative trait loci (mQTLs) influencing promoter DNA methylation of alcohol dependence risk genes
Zhang H, Wang F, Kranzler HR, Yang C, Xu H, Wang Z, Zhao H, Gelernter J. Identification of methylation quantitative trait loci (mQTLs) influencing promoter DNA methylation of alcohol dependence risk genes. Human Genetics 2014, 133: 1093-1104. PMID: 24889829, PMCID: PMC4127343, DOI: 10.1007/s00439-014-1452-2.Peer-Reviewed Original ResearchConceptsMethylation quantitative trait lociQuantitative trait lociDNA methylationTrait lociSignificant methylation quantitative trait lociSequence variantsRisk genesGene expression regulationGenome-wide association studiesGenome-wide genotype dataPromoter DNA methylationAD risk genesGene promoter regionExpression QTLsExpression regulationGenetic variationPromoter CpGsPromoter regionChild Abuse, Depression, and Methylation in Genes Involved With Stress, Neural Plasticity, and Brain Circuitry
Weder N, Zhang H, Jensen K, Yang BZ, Simen A, Jackowski A, Lipschitz D, Douglas-Palumberi H, Ge M, Perepletchikova F, O'Loughlin K, Hudziak JJ, Gelernter J, Kaufman J. Child Abuse, Depression, and Methylation in Genes Involved With Stress, Neural Plasticity, and Brain Circuitry. Journal Of The American Academy Of Child & Adolescent Psychiatry 2014, 53: 417-424.e5. PMID: 24655651, PMCID: PMC4126411, DOI: 10.1016/j.jaac.2013.12.025.Peer-Reviewed Original ResearchConceptsTubulin Polymerization Promoting ProteinCandidate genesEpigenetic changesMethylation sitesGenome-wide methylation studyMultiple methylation sitesK BeadChip arraySaliva-derived DNAEpigenetic mechanismsK BeadChipBeadChip arrayEpigenetic markersStress responseMethylation studiesCpG sitesGenesNeural circuitry developmentMethylationId-3Whole genome testingNeural plasticityGRIN1Genome testingPlasticityGlutamate receptors
2013
Sex-biased methylome and transcriptome in human prefrontal cortex
Xu H, Wang F, Liu Y, Yu Y, Gelernter J, Zhang H. Sex-biased methylome and transcriptome in human prefrontal cortex. Human Molecular Genetics 2013, 23: 1260-1270. PMID: 24163133, PMCID: PMC3919013, DOI: 10.1093/hmg/ddt516.Peer-Reviewed Original ResearchConceptsDNA methylationGene expressionSex-biased DNA methylationMultiple test correctionGenome-wide DNA methylationGene Ontology annotationsDAVID functional annotation analysisFunctional annotation analysisRibosome structurePhenotypic variationAnnotation analysisGO termsProtein translationRNA bindingOntology annotationsHost genesDifferential methylationExpression correlationTranscriptomic profilesDifferential brain developmentDifferential expressionMethylation levelsGenesMethylationTranscriptomeProfiling of Childhood Adversity-Associated DNA Methylation Changes in Alcoholic Patients and Healthy Controls
Zhang H, Wang F, Kranzler HR, Zhao H, Gelernter J. Profiling of Childhood Adversity-Associated DNA Methylation Changes in Alcoholic Patients and Healthy Controls. PLOS ONE 2013, 8: e65648. PMID: 23799031, PMCID: PMC3683055, DOI: 10.1371/journal.pone.0065648.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAlcoholismAldehyde DehydrogenaseAldehyde Dehydrogenase 1 FamilyBlack or African AmericanCase-Control StudiesChild AbuseCpG IslandsDNA MethylationEpigenesis, GeneticFemaleGenetic Association StudiesGenetic Predisposition to DiseaseHumansMaleMiddle AgedNerve Tissue ProteinsNociceptin ReceptorPolymorphism, Single NucleotidePromoter Regions, GeneticReceptors, NicotinicReceptors, OpioidRetinal DehydrogenaseRGS ProteinsSequence Analysis, DNATranscription, GeneticWhite PeopleYoung AdultConceptsHealthy controlsAD patientsChildhood adversityDNA methylation changesIllumina GoldenGate methylation arrayPeripheral blood DNA methylation levelsBlood DNA methylation levelsAlcoholic patientsControl subjectsLinear regression analysisMethylation changesPatientsMethylation levelsPromoter regionEA casesBonferroni correctionRegression analysisP-valueAfrican AmericansOverall methylation levelsChild Abuse and Epigenetic Mechanisms of Disease Risk
Yang BZ, Zhang H, Ge W, Weder N, Douglas-Palumberi H, Perepletchikova F, Gelernter J, Kaufman J. Child Abuse and Epigenetic Mechanisms of Disease Risk. American Journal Of Preventive Medicine 2013, 44: 101-107. PMID: 23332324, PMCID: PMC3758252, DOI: 10.1016/j.amepre.2012.10.012.Peer-Reviewed Original Research
2012
Array‐Based Profiling of DNA Methylation Changes Associated with Alcohol Dependence
Zhang H, Herman AI, Kranzler HR, Anton RF, Zhao H, Zheng W, Gelernter J. Array‐Based Profiling of DNA Methylation Changes Associated with Alcohol Dependence. Alcohol Clinical And Experimental Research 2012, 37: e108-e115. PMID: 22924764, PMCID: PMC3511647, DOI: 10.1111/j.1530-0277.2012.01928.x.Peer-Reviewed Original Research