2024
Multi-omics profiling of DNA methylation and gene expression alterations in human cocaine use disorder
Zillich E, Belschner H, Avetyan D, Andrade-Brito D, Martínez-Magaña J, Frank J, Mechawar N, Turecki G, Cabana-Domínguez J, Fernàndez-Castillo N, Cormand B, Montalvo-Ortiz J, Nöthen M, Hansson A, Rietschel M, Spanagel R, Witt S, Zillich L. Multi-omics profiling of DNA methylation and gene expression alterations in human cocaine use disorder. Translational Psychiatry 2024, 14: 428. PMID: 39384764, PMCID: PMC11464785, DOI: 10.1038/s41398-024-03139-9.Peer-Reviewed Original ResearchConceptsCocaine use disorderUse disorderAlternative splicingHuman prefrontal cortexProfiling of DNA methylationBrodmann area 9Differential alternative splicingDeregulated biological processesPostmortem brain tissueMulti-omics approachCocaine intakeMulti-omics studiesPrefrontal cortexBrain alterationsMulti-omics profilingGene expression alterationsArea 9Fatty acid metabolismReceptor-targeting drugsSpliced transcriptsEpigenome-wideDNA methylationNeuronal morphogenesisAS changesDrug repositioning analysisA phenome-wide association and Mendelian randomisation study of alcohol use variants in a diverse cohort comprising over 3 million individuals
Jennings M, Martínez-Magaña J, Courchesne-Krak N, Cupertino R, Vilar-Ribó L, Bianchi S, Hatoum A, Atkinson E, Giusti-Rodriguez P, Montalvo-Ortiz J, Gelernter J, Artigas M, 23andMe I, Aslibekyan S, Auton A, Babalola E, Bell R, Bielenberg J, Bryc K, Bullis E, Coker D, Partida G, Dhamija D, Das S, Elson S, Eriksson N, Filshtein T, Fitch A, Fletez-Brant K, Fontanillas P, Freyman W, Granka J, Heilbron K, Hernandez A, Hicks B, Hinds D, Jewett E, Jiang Y, Kukar K, Kwong A, Lin K, Llamas B, Lowe M, McCreight J, McIntyre M, Micheletti S, Moreno M, Nandakumar P, Nguyen D, Noblin E, O'Connell J, Petrakovitz A, Poznik G, Reynoso A, Schumacher M, Shastri A, Shelton J, Shi J, Shringarpure S, Su Q, Tat S, Tchakouté C, Tran V, Tung J, Wang X, Wang W, Weldon C, Wilton P, Wong C, Elson S, Edenberg H, Fontanillas P, Palmer A, Sanchez-Roige S. A phenome-wide association and Mendelian randomisation study of alcohol use variants in a diverse cohort comprising over 3 million individuals. EBioMedicine 2024, 103: 105086. PMID: 38580523, PMCID: PMC11121167, DOI: 10.1016/j.ebiom.2024.105086.Peer-Reviewed Original ResearchConceptsMultiple domains of healthDomains of healthEffects of alcohol consumptionAlcohol consumptionHealth outcomesPhenome-wide association studyAlcohol-related behaviorsCardio-metabolic healthPotential causal effectMendelian randomisation studiesGenome-wide association studiesPhenome-wide associationMR analysisPheWAS associationsMultiple domainsHypothesis-free approachPreventive medicineDiverse cohortPheWASAssociation studiesHealthReproductive healthAlcohol behaviorConsequences of drinkingEuropean cohort
2023
Positive personality traits moderate persistent high alcohol consumption, determined by polygenic risk in U.S. military veterans: results from a 10-year, population-based, observational cohort study
Na P, Zhou H, Montalvo-Ortiz J, Cabrera-Mendoza B, Petrakis I, Krystal J, Polimanti R, Gelernter J, Pietrzak R. Positive personality traits moderate persistent high alcohol consumption, determined by polygenic risk in U.S. military veterans: results from a 10-year, population-based, observational cohort study. Psychological Medicine 2023, 53: 7893-7901. PMID: 37642191, DOI: 10.1017/s003329172300199x.Peer-Reviewed Original ResearchProfiling 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 analysisTrajectories of alcohol consumption in U.S. military veterans: Results from a 10-year population-based longitudinal study
Na P, Montalvo-Ortiz J, Petrakis I, Krystal J, Polimanti R, Gelernter J, Pietrzak R. Trajectories of alcohol consumption in U.S. military veterans: Results from a 10-year population-based longitudinal study. Drug And Alcohol Dependence 2023, 246: 109833. PMID: 36963160, PMCID: PMC10811960, DOI: 10.1016/j.drugalcdep.2023.109833.Peer-Reviewed Original ResearchConceptsAlcohol consumption groupCurrent mental health treatmentDysphoric arousal symptomsMental health treatmentUS veteransAlcohol consumptionHealth treatmentConsumption groupArousal symptomsYounger agePopulation-based longitudinal studyPublic health problemLongitudinal studyExcessive alcohol consumptionAlcohol use disorderPosttraumatic stress disorderU.S. military veteransMedical comorbiditiesChronic courseNational HealthClose monitoringUse disordersHealth problemsVeterans StudyStress disorder
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 populationAssociation of Symptoms of Posttraumatic Stress Disorder and GrimAge, an Epigenetic Marker of Mortality Risk, in US Military Veterans.
Na PJ, Montalvo-Ortiz JL, Nagamatsu ST, Southwick SM, Krystal JH, Gelernter J, Pietrzak RH. Association of Symptoms of Posttraumatic Stress Disorder and GrimAge, an Epigenetic Marker of Mortality Risk, in US Military Veterans. The Journal Of Clinical Psychiatry 2022, 83 PMID: 35802930, PMCID: PMC10859885, DOI: 10.4088/jcp.21br14309.Peer-Reviewed Original ResearchThe role of alcohol intake in the pharmacogenetics of treatment with clozapine
Monroy-Jaramillo N, Martínez-Magaña JJ, Pérez-Aldana BE, Ortega-Vázquez A, Montalvo-Ortiz J, López-López M. The role of alcohol intake in the pharmacogenetics of treatment with clozapine. Pharmacogenomics 2022, 23: 371-392. PMID: 35311547, DOI: 10.2217/pgs-2022-0006.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsAdverse reactionsAlcohol intakeConcomitant useSevere adverse reactionsGood therapeutic effectPrecision medicine approachRefractory psychosisAtypical antipsychoticsInterindividual responseTherapeutic effectClozapineMedicine approachPharmacogenetic studiesSignificant riskIntakePatientsGenetic variantsPharmacogeneticsAntipsychoticsPsychosisCYP1A2ReceptorsEpigenome-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
DNA methylation changes in African American women with a history of preterm birth from the InterGEN study
Barcelona V, Montalvo-Ortiz JL, Wright ML, Nagamatsu ST, Dreisbach C, Crusto CA, Sun YV, Taylor JY. DNA methylation changes in African American women with a history of preterm birth from the InterGEN study. BMC Genomic Data 2021, 22: 30. PMID: 34482817, PMCID: PMC8418749, DOI: 10.1186/s12863-021-00988-x.Peer-Reviewed Original ResearchConceptsPreterm birthHealth disordersFull-term birthCentral nervous systemEpigenome-wide association studiesAfrican American womenInterGEN StudyBackgroundPreterm birthMaternal moodWomen 3Cardiovascular diseaseIndependent cohortPhysiologic mechanismsNervous systemAfrican American mothersSignificant CpG sitesEWAS approachWomenBirthSensory processingDNA methylationLong-term epigenetic effectsAmerican womenCommon outcomeFurther studies
2020
Attachment Style Moderates Polygenic Risk for Posttraumatic Stress in United States Military Veterans: Results From the National Health and Resilience in Veterans Study
Tamman AJF, Wendt FR, Pathak GA, Krystal JH, Montalvo-Ortiz JL, Southwick SM, Sippel LM, Gelernter J, Polimanti R, Pietrzak RH. Attachment Style Moderates Polygenic Risk for Posttraumatic Stress in United States Military Veterans: Results From the National Health and Resilience in Veterans Study. Biological Psychiatry 2020, 89: 878-887. PMID: 33276944, DOI: 10.1016/j.biopsych.2020.09.018.Peer-Reviewed Original ResearchAdvancing Alcohol Genetics Research: One Genome-wide Association Study at a Time and Beyond
Montalvo-Ortiz JL. Advancing Alcohol Genetics Research: One Genome-wide Association Study at a Time and Beyond. Biological Psychiatry 2020, 87: 590-591. PMID: 32164913, DOI: 10.1016/j.biopsych.2020.01.003.Commentaries, Editorials and LettersTubulin Polymerization Promoting Protein (TPPP) gene methylation and corpus callosum measures in maltreated children
de Araújo CM, Hudziak J, Crocetti D, Wymbs NF, Montalvo-Ortiz JL, Orr C, Albaugh MD, Althoff RR, O'Loughlin K, Holbrook H, Garavan H, Yang BZ, Mostofsky S, Jackowski A, Lee RS, Gelernter J, Kaufman J. Tubulin Polymerization Promoting Protein (TPPP) gene methylation and corpus callosum measures in maltreated children. Psychiatry Research Neuroimaging 2020, 298: 111058. PMID: 32120304, PMCID: PMC11079625, DOI: 10.1016/j.pscychresns.2020.111058.Peer-Reviewed Original ResearchConceptsStress-related psychiatric disordersCorpus callosum measuresFractional anisotropyPsychiatric disordersTrauma experiencesWhite matter tractsChild trauma experiencesBrain changesLarger studyRelevant covariatesAtlas-based approachSplenium fractional anisotropyDNA specimensMultiple comparisonsGene methylationDisordersChildrenCurrent studySocial supports moderate the effects of child adversity on neural correlates of threat processing
Wymbs NF, Orr C, Albaugh MD, Althoff RR, O’Loughlin K, Holbrook H, Garavan H, Montalvo-Ortiz JL, Mostofsky S, Hudziak J, Kaufman J. Social supports moderate the effects of child adversity on neural correlates of threat processing. Child Abuse & Neglect 2020, 102: 104413. PMID: 32065988, PMCID: PMC8060780, DOI: 10.1016/j.chiabu.2020.104413.Peer-Reviewed Original ResearchConceptsFunctional magnetic resonance imagingThreat processingAnterior cingulate cortexSocial supportEmotion regulationNeural correlatesEmotional Go-Nogo taskGo-NoGo taskPositive social supportChildren ages 7Forms of adversityKey brain regionsAdverse experiencesFacial stimuliThreat stimuliNeural processingBrain systemsBrain activationModerate adversitySevere adversityAnterior insulaConjunction analysisLeft amygdalaOrbitofrontal cortexActivation foci
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 proportionAccelerated DNA Methylation Aging in U.S. Military Veterans: Results From the National Health and Resilience in Veterans Study
Tamman AJF, Montalvo-Ortiz JL, Southwick SM, Krystal JH, Levy BR, Pietrzak RH. Accelerated DNA Methylation Aging in U.S. Military Veterans: Results From the National Health and Resilience in Veterans Study. American Journal Of Geriatric Psychiatry 2019, 27: 528-532. PMID: 30792041, DOI: 10.1016/j.jagp.2019.01.001.Peer-Reviewed Original ResearchConceptsNational HealthPsychosocial factorsVeterans StudyMale U.S. veteransLifetime trauma burdenAccelerated DNA methylation agingDNA methylation agingU.S. military veteransMethylation agingTrauma burdenU.S. veteransPrevention effortsAdditional correlatesNegative beliefsMilitary veteransSexual traumaVeteransTraumatic stressDNA methylationHealthChild sexual traumaBody massRepresentative sample
2018
Adverse 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