Featured Publications
Genome-wide association study of alcohol consumption and use disorder in 274,424 individuals from multiple populations
Kranzler HR, Zhou H, Kember RL, Vickers Smith R, Justice AC, Damrauer S, Tsao PS, Klarin D, Baras A, Reid J, Overton J, Rader DJ, Cheng Z, Tate JP, Becker WC, Concato J, Xu K, Polimanti R, Zhao H, Gelernter J. Genome-wide association study of alcohol consumption and use disorder in 274,424 individuals from multiple populations. Nature Communications 2019, 10: 1499. PMID: 30940813, PMCID: PMC6445072, DOI: 10.1038/s41467-019-09480-8.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesAssociation studiesMillion Veteran Program sampleGenetic correlationsWide significant lociSignificant genetic correlationsPolygenic risk scoresCell type groupSignificant lociHeritable traitEnrichment analysisTraitsMultiple populationsLociPhenotypeProgram samples
2024
Genome-wide association study of the common retinal disorder epiretinal membrane: Significant risk loci in each of three American populations
Gelernter J, Levey D, Galimberti M, Harrington K, Zhou H, Adhikari K, Gupta P, Program V, Gaziano J, Eliott D, Stein M. Genome-wide association study of the common retinal disorder epiretinal membrane: Significant risk loci in each of three American populations. Cell Genomics 2024, 4: 100582. PMID: 38870908, PMCID: PMC11228954, DOI: 10.1016/j.xgen.2024.100582.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesMillion Veteran ProgramRisk lociAssociation studiesTrans-ancestry meta-analysisSignificant risk lociPathway enrichment analysisEpiretinal membraneTrans-ancestryGenome-wideMultiple traitsGenetic associationEnrichment analysisGene expressionEuropean AmericansLoss of visual acuityVeteran ProgramGenetic correlationsLociBiological mechanismsAmerican populationVisual acuityRetinal conditionsControl individualsRetinal surfaceAssociation between cannabis use and brain structure and function: an observational and Mendelian randomisation study
Ishrat S, Levey D, Gelernter J, Ebmeier K, Topiwala A. Association between cannabis use and brain structure and function: an observational and Mendelian randomisation study. BMJ Mental Health 2024, 27: e301065. PMID: 39477366, PMCID: PMC11529520, DOI: 10.1136/bmjment-2024-301065.Peer-Reviewed Original ResearchConceptsCannabis useBrain structuresFunctional connectivityHistory of cannabis useResting-state functional connectivityMeasures of brain structureLifetime cannabis useCentral executive networkLifetime cannabis usersWhite matter integrityGenu of the corpus callosumMendelian randomisation analysisAssociated with multiple measuresPoorer white matter integrityInvestigate potential causal relationshipsCannabis usersExecutive networkBrain regionsImaging-derived phenotypesBrain healthCannabisRandomisation analysesTwo-sample Mendelian randomisation analysisFractional anisotropyYoung adulthood
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 ResearchConceptsGenome-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 regressionTraits
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 ResearchConceptsOpioid 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 RevisionGenotyping Array Design and Data Quality Control in the Million Veteran Program
Hunter-Zinck H, Shi Y, Li M, Gorman BR, Ji SG, Sun N, Webster T, Liem A, Hsieh P, Devineni P, Karnam P, Gong X, Radhakrishnan L, Schmidt J, Assimes TL, Huang J, Pan C, Humphries D, Brophy M, Moser J, Muralidhar S, Huang GD, Przygodzki R, Concato J, Gaziano JM, Gelernter J, O’Donnell C, Hauser ER, Zhao H, O’Leary T, Program V, Tsao PS, Pyarajan S. Genotyping Array Design and Data Quality Control in the Million Veteran Program. American Journal Of Human Genetics 2020, 106: 535-548. PMID: 32243820, PMCID: PMC7118558, DOI: 10.1016/j.ajhg.2020.03.004.Peer-Reviewed Original ResearchConceptsMillion Veteran ProgramGenome-wide association studiesGenome-wide scanHigh-quality genotypesArray-based genotypingWhole-genome sequencingNon-European individualsAssociation studiesGenetic markersOmics assaysAxiom arrayDownstream analysisVeteran ProgramCommon variantsGenetic associationAfrican American ancestryAmerican ancestryMVP cohortRare variantsSingle assayDiversityFurther data releasesLarge biobanksPromising resourceQuality controlReproducible Genetic Risk Loci for Anxiety: Results From ∼200,000 Participants in the Million Veteran Program
Levey DF, Gelernter J, Polimanti R, Zhou H, Cheng Z, Aslan M, Quaden R, Concato J, Radhakrishnan K, Bryois J, Sullivan PF, Stein M. Reproducible Genetic Risk Loci for Anxiety: Results From ∼200,000 Participants in the Million Veteran Program. American Journal Of Psychiatry 2020, 177: 223-232. PMID: 31906708, PMCID: PMC7869502, DOI: 10.1176/appi.ajp.2019.19030256.Peer-Reviewed Original ResearchConceptsNovel genome-wide significant associationsGene expressionGenome-wide significant signalsGenome-wide significant associationMillion Veteran ProgramWide association studyGenetic risk lociSignificant genetic correlationsGenetic risk mechanismsGenetic architectureGlobal regulatorChromosome 3Risk lociChromosome 6Chromosome 7Association studiesLargest GWASLarge biobanksGlobal regulationGenetic correlationsContinuous traitsVeteran ProgramGWASsLociPrevious GWASs
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 rateGenome-wide Association Study of Maximum Habitual Alcohol Intake in >140,000 U.S. European and African American Veterans Yields Novel Risk Loci
Gelernter J, Sun N, Polimanti R, Pietrzak RH, Levey DF, Lu Q, Hu Y, Li B, Radhakrishnan K, Aslan M, Cheung KH, Li Y, Rajeevan N, Sayward F, Harrington K, Chen Q, Cho K, Honerlaw J, Pyarajan S, Lencz T, Quaden R, Shi Y, Hunter-Zinck H, Gaziano JM, Kranzler HR, Concato J, Zhao H, Stein MB, Program D, Program M. Genome-wide Association Study of Maximum Habitual Alcohol Intake in >140,000 U.S. European and African American Veterans Yields Novel Risk Loci. Biological Psychiatry 2019, 86: 365-376. PMID: 31151762, PMCID: PMC6919570, DOI: 10.1016/j.biopsych.2019.03.984.Peer-Reviewed Original ResearchConceptsAdditional genome-wide significant lociRisk lociWide association study (GWAS) analysisAssociation studiesGenome-wide significant lociGenome-wide association studiesGenetic correlationsWide association studyNovel risk lociAlcohol-related traitsStrong statistical supportSmoking-related traitsAdditional genomesSignificant lociPancreatic delta cellsChromosome 4Chromosome 11Protein productsChromosome 8Quantitative phenotypesMillion Veteran ProgramVeterans Affairs Million Veteran ProgramLociCell typesChromosome 17Evidence of causal effect of major depression on alcohol dependence: findings from the psychiatric genomics consortium
Polimanti R, Peterson RE, Ong JS, MacGregor S, Edwards AC, Clarke TK, Frank J, Gerring Z, Gillespie NA, Lind PA, Maes HH, Martin NG, Mbarek H, Medland SE, Streit F, Agrawal A, Edenberg H, Kendler K, Lewis C, Sullivan P, Wray N, Gelernter J, Derks E. Evidence of causal effect of major depression on alcohol dependence: findings from the psychiatric genomics consortium. Psychological Medicine 2019, 49: 1218-1226. PMID: 30929657, PMCID: PMC6565601, DOI: 10.1017/s0033291719000667.Peer-Reviewed Original ResearchConceptsMajor depressionAlcohol dependenceAlcohol consumptionPsychiatric Genomics ConsortiumImportant public health concernMendelian randomizationPublic health concernUK BiobankClinical associationsHealth concernMR analysisReverse causationCausal roleNon-significant resultsCausal relationshipGenetic liabilityGenomics ConsortiumLinkage disequilibrium score regressionIntervention effortsGenomics of posttraumatic stress disorder in veterans: Methods and rationale for Veterans Affairs Cooperative Study #575B
Radhakrishnan K, Aslan M, Harrington KM, Pietrzak RH, Huang G, Muralidhar S, Cho K, Quaden R, Gagnon D, Pyarajan S, Sun N, Zhao H, Gaziano M, Concato J, Stein MB, Gelernter J. Genomics of posttraumatic stress disorder in veterans: Methods and rationale for Veterans Affairs Cooperative Study #575B. International Journal Of Methods In Psychiatric Research 2019, 28: e1767. PMID: 30767326, PMCID: PMC6877159, DOI: 10.1002/mpr.1767.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAged, 80 and overAlgorithmsCase-Control StudiesFemaleGenetic Predisposition to DiseaseGenomicsHumansInterviews as TopicMaleMiddle AgedPolymorphism, Single NucleotidePsychiatric Status Rating ScalesStress Disorders, Post-TraumaticSurveys and QuestionnairesUnited StatesUnited States Department of Veterans AffairsVeteransYoung Adult
2018
GWAS of lifetime cannabis use reveals new risk loci, genetic overlap with psychiatric traits, and a causal effect of schizophrenia liability
Pasman JA, Verweij KJH, Gerring Z, Stringer S, Sanchez-Roige S, Treur JL, Abdellaoui A, Nivard MG, Baselmans BML, Ong JS, Ip HF, van der Zee MD, Bartels M, Day FR, Fontanillas P, Elson SL, the 23andMe Research Team, de Wit H, Davis LK, MacKillop J, The Substance Use Disorders Working Group of the Psychiatric Genomics Consortium, International Cannabis Consortium, Derringer JL, Branje SJT, Hartman CA, Heath AC, van Lier PAC, Madden PAF, Mägi R, Meeus W, Montgomery GW, Oldehinkel AJ, Pausova Z, Ramos-Quiroga JA, Paus T, Ribases M, Kaprio J, Boks MPM, Bell JT, Spector TD, Gelernter J, Boomsma DI, Martin NG, MacGregor S, Perry JRB, Palmer AA, Posthuma D, Munafò MR, Gillespie NA, Derks EM, Vink JM. GWAS of lifetime cannabis use reveals new risk loci, genetic overlap with psychiatric traits, and a causal effect of schizophrenia liability. Nature Neuroscience 2018, 21: 1161-1170. PMID: 30150663, PMCID: PMC6386176, DOI: 10.1038/s41593-018-0206-1.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAged, 80 and overCell Adhesion MoleculesDatabases, GeneticFemaleGene Expression RegulationGenetic Predisposition to DiseaseGenome-Wide Association StudyGenotypeHumansMaleMarijuana AbuseMendelian Randomization AnalysisMental HealthMiddle AgedPolymorphism, Single NucleotideRisk-TakingSchizophreniaYoung AdultConceptsGenome-wide association studiesNew risk lociLarge genome-wide association studiesGene-based testsIndependent single nucleotide polymorphismsDifferent expression levelsSignificant genetic correlationsHealth-related traitsSingle nucleotide polymorphismsEtiology of cannabisHeritable traitRisk lociSignificant genesAssociation studiesGenetic correlationsPsychiatric traitsGenetic variantsNucleotide polymorphismsGenetic overlapExpression levelsTraitsGenesNew insightsSchizophrenia riskMendelian randomization analysisAUDIT‐C and ICD codes as phenotypes for harmful alcohol use: association with ADH1B polymorphisms in two US populations
Justice AC, Smith RV, Tate JP, McGinnis K, Xu K, Becker WC, Lee K, Lynch K, Sun N, Concato J, Fiellin DA, Zhao H, Gelernter J, Kranzler HR, Program O. AUDIT‐C and ICD codes as phenotypes for harmful alcohol use: association with ADH1B polymorphisms in two US populations. Addiction 2018, 113: 2214-2224. PMID: 29972609, PMCID: PMC6226338, DOI: 10.1111/add.14374.Peer-Reviewed Original Research
2017
Association 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 ResearchCortical β-amyloid burden, gray matter, and memory in adults at varying APOE ε4 risk for Alzheimer's disease
Mecca AP, Barcelos NM, Wang S, Brück A, Nabulsi N, Planeta-Wilson B, Nadelmann J, Benincasa AL, Ropchan J, Huang Y, Gelernter J, Van Ness PH, Carson RE, van Dyck CH. Cortical β-amyloid burden, gray matter, and memory in adults at varying APOE ε4 risk for Alzheimer's disease. Neurobiology Of Aging 2017, 61: 207-214. PMID: 29111487, PMCID: PMC5722236, DOI: 10.1016/j.neurobiolaging.2017.09.027.Peer-Reviewed Original ResearchConceptsΒ-amyloid burdenMiddle-aged individualsAβ burdenEpisodic memory performanceCognitive declineGM fractionCortical β-amyloid burdenBrain magnetic resonance imagingFirst-degree family historyCortical Aβ burdenGray matter fractionNormal middle-aged individualsSubsequent cognitive declineMagnetic resonance imagingPositron emission tomographyAPOE ε3ε3Cortical AβCerebral amyloidosisAPOE genotypeFamily historyPreclinical ADMemory performanceNeuropsychological testingAlzheimer's diseaseGray matterGenome-wide association study across European and African American ancestries identifies a SNP in DNMT3B contributing to nicotine dependence
Hancock DB, Guo Y, Reginsson GW, Gaddis NC, Lutz SM, Sherva R, Loukola A, Minica CC, Markunas CA, Han Y, Young KA, Gudbjartsson DF, Gu F, McNeil DW, Qaiser B, Glasheen C, Olson S, Landi MT, Madden PAF, Farrer LA, Vink J, Saccone NL, Neale MC, Kranzler HR, McKay J, Hung RJ, Amos CI, Marazita ML, Boomsma DI, Baker TB, Gelernter J, Kaprio J, Caporaso NE, Thorgeirsson TE, Hokanson JE, Bierut LJ, Stefansson K, Johnson EO. Genome-wide association study across European and African American ancestries identifies a SNP in DNMT3B contributing to nicotine dependence. Molecular Psychiatry 2017, 23: 1911-1919. PMID: 28972577, PMCID: PMC5882602, DOI: 10.1038/mp.2017.193.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesAssociation studiesGenotype-Tissue Expression (GTEx) projectDNA methyltransferase genesAcetylcholine receptor genesNicotine dependenceMethyltransferase geneExpression projectCHRNB4 genesHeritable traitAdditional lociProxy phenotypeSequence variantsDNMT3B expressionGenesReceptor geneSquamous cell lung carcinomaCHRNA5-CHRNA3African American ancestryNovel associationsInternational Lung Cancer ConsortiumCell lung carcinomaLociAmerican ancestryAdult cerebellumOxytocin 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
Genome-wide association study of lifetime cannabis use based on a large meta-analytic sample of 32 330 subjects from the International Cannabis Consortium
Stringer S, Minică CC, Verweij KJ, Mbarek H, Bernard M, Derringer J, van Eijk KR, Isen JD, Loukola A, Maciejewski DF, Mihailov E, van der Most PJ, Sánchez-Mora C, Roos L, Sherva R, Walters R, Ware JJ, Abdellaoui A, Bigdeli TB, Branje SJ, Brown SA, Bruinenberg M, Casas M, Esko T, Garcia-Martinez I, Gordon SD, Harris JM, Hartman CA, Henders AK, Heath AC, Hickie IB, Hickman M, Hopfer CJ, Hottenga JJ, Huizink AC, Irons DE, Kahn RS, Korhonen T, Kranzler HR, Krauter K, van Lier PA, Lubke GH, Madden PA, Mägi R, McGue MK, Medland SE, Meeus WH, Miller MB, Montgomery GW, Nivard MG, Nolte IM, Oldehinkel AJ, Pausova Z, Qaiser B, Quaye L, Ramos-Quiroga JA, Richarte V, Rose RJ, Shin J, Stallings MC, Stiby AI, Wall TL, Wright MJ, Koot HM, Paus T, Hewitt JK, Ribasés M, Kaprio J, Boks MP, Snieder H, Spector T, Munafò MR, Metspalu A, Gelernter J, Boomsma DI, Iacono WG, Martin NG, Gillespie NA, Derks EM, Vink JM. Genome-wide association study of lifetime cannabis use based on a large meta-analytic sample of 32 330 subjects from the International Cannabis Consortium. Translational Psychiatry 2016, 6: e769-e769. PMID: 27023175, PMCID: PMC4872459, DOI: 10.1038/tp.2016.36.Peer-Reviewed Original ResearchConceptsLifetime cannabis useCannabis useInternational Cannabis ConsortiumLifetime cannabisIndividual differencesAutism disorderOccasional cannabisCannabis initiationSubstance useEffect sizeSocial consequencesCannabisLifetime cigarette smokingCigarette useReplication sampleGene-based testsCigarette smokingPsychoactive substancesIllicit psychoactive substancesSNP effect sizesFrequent useGenome-wide association studiesGenetic correlationsGenome-wide association dataAbuse
2014
Differentially co-expressed genes in postmortem prefrontal cortex of individuals with alcohol use disorders: influence on alcohol metabolism-related pathways
Zhang H, Wang F, Xu H, Liu Y, Liu J, Zhao H, Gelernter J. Differentially co-expressed genes in postmortem prefrontal cortex of individuals with alcohol use disorders: influence on alcohol metabolism-related pathways. Human Genetics 2014, 133: 1383-1394. PMID: 25073604, PMCID: PMC4185230, DOI: 10.1007/s00439-014-1473-x.Peer-Reviewed Original ResearchConceptsCo-expressed genesGenome-wide association studiesHumanHT-12 v4 Expression BeadChipGene modulesPostmortem prefrontal cortexGene co-expression network analysisCo-expression network analysisDAVID Bioinformatics ResourcesGene expression alterationsMetabolism-related pathwaysV4 Expression BeadChipCellular functionsTranscriptome profilesFatty acid metabolismBioinformatics resourcesEnrichment analysisExpression probesBiological pathwaysAssociation studiesAldehyde detoxificationExpression alterationsGenesMitochondrial functionBrain reward regionsAcid metabolismNovel QTL at chromosome 6p22 for alcohol consumption: Implications for the genetic liability of alcohol use disorders
Kos MZ, Glahn DC, Carless MA, Olvera R, McKay DR, Quillen EE, Gelernter J, Chen X, Deng H, Kent JW, Dyer TD, Göring HH, Curran JE, Duggirala R, Blangero J, Almasy L. Novel QTL at chromosome 6p22 for alcohol consumption: Implications for the genetic liability of alcohol use disorders. American Journal Of Medical Genetics Part B Neuropsychiatric Genetics 2014, 165: 294-302. PMID: 24692236, PMCID: PMC4172449, DOI: 10.1002/ajmg.b.32231.Peer-Reviewed Original ResearchConceptsSan Antonio Family StudyGenome-wide SNPsSignificant SNP associationsSignificant pleiotropic effectsCompelling candidate genesStrong genetic correlationPotential risk locusNovel QTLChromosome 6p22.3Significant QTLGene actionChromosome regionsChromosome 4Heritable phenotypesCandidate genesRisk lociLinkage signalChromosome 6p22QTLSNP associationsLinkage regionGenetic correlationsSusceptibility genesPleiotropic effectsGenes