2024
Association patterns of antisocial personality disorder across substance use disorders
Low A, Stiltner B, Nunez Y, Adhikari K, Deak J, Pietrzak R, Kranzler H, Gelernter J, Polimanti R. Association patterns of antisocial personality disorder across substance use disorders. Translational Psychiatry 2024, 14: 346. PMID: 39198385, PMCID: PMC11358160, DOI: 10.1038/s41398-024-03054-z.Peer-Reviewed Original ResearchConceptsAntisocial personality disorderSubstance use disordersPersonality disorderUse disorderAssociation of antisocial personality disorderPresence of antisocial personality disorderPrevalence of antisocial personality disorderHazardous useDSM-5 SUD diagnosesSubstance use disorder severityDiagnostic criteriaInteraction effects with sexTobacco use disorderDSM-5Association of alcoholSUD diagnosisDisordersCocaineRacial/ethnic backgroundsIndividualsCocUDSeverityCannabisAssociation patternsAssociationDiversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program
Verma A, Huffman J, Rodriguez A, Conery M, Liu M, Ho Y, Kim Y, Heise D, Guare L, Panickan V, Garcon H, Linares F, Costa L, Goethert I, Tipton R, Honerlaw J, Davies L, Whitbourne S, Cohen J, Posner D, Sangar R, Murray M, Wang X, Dochtermann D, Devineni P, Shi Y, Nandi T, Assimes T, Brunette C, Carroll R, Clifford R, Duvall S, Gelernter J, Hung A, Iyengar S, Joseph J, Kember R, Kranzler H, Kripke C, Levey D, Luoh S, Merritt V, Overstreet C, Deak J, Grant S, Polimanti R, Roussos P, Shakt G, Sun Y, Tsao N, Venkatesh S, Voloudakis G, Justice A, Begoli E, Ramoni R, Tourassi G, Pyarajan S, Tsao P, O'Donnell C, Muralidhar S, Moser J, Casas J, Bick A, Zhou W, Cai T, Voight B, Cho K, Gaziano J, Madduri R, Damrauer S, Liao K. Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program. Science 2024, 385: eadj1182. PMID: 39024449, DOI: 10.1126/science.adj1182.Peer-Reviewed Original ResearchConceptsMillion Veteran ProgramNon-European populationsVeteran ProgramGenetic architectureAtlas of genetic associationsVeterans Affairs Million Veteran ProgramVA Million Veteran ProgramGenomic risk lociGenome-wide associationHuman genetic studiesHealth disparitiesUnited States veteransCausal variantsRisk lociGenetic insightsGenetic studiesGenetic associationGenetic causeStates veteransDiverse populationsDisease factorsLack of inclusionLongitudinal studyParticipantsTraitsGenetic contribution to the comorbidity between attention-deficit/hyperactivity disorder and substance use disorders
Koller D, Mitjans M, Kouakou M, Friligkou E, Cabrera-Mendoza B, Deak J, Llonga N, Pathak G, Stiltner B, Løkhammer S, Levey D, Zhou H, Hatoum A, Kember R, Kranzler H, Stein M, Corominas R, Demontis D, Artigas M, Ramos-Quiroga J, Gelernter J, Ribasés M, Cormand B, Polimanti R. Genetic contribution to the comorbidity between attention-deficit/hyperactivity disorder and substance use disorders. Psychiatry Research 2024, 333: 115758. PMID: 38335780, PMCID: PMC11157987, DOI: 10.1016/j.psychres.2024.115758.Peer-Reviewed Original ResearchConceptsUse disorderGenome-wide association studiesGenomic structural equation modelingCannabis use disorderAlcohol Use Disorders Identification TestAttention-deficit/hyperactivity disorderAlcohol use disorderProblematic alcohol useSubstance use disordersTwo-sample Mendelian randomization analysisLinkage disequilibrium score regression analysisDisorders Identification TestMendelian randomization analysisAssociated with increased oddsOdds of ADHDOpioid use disorderAttention-deficit/hyperactivityGWAS meta-analysesAlcohol dependenceStructural equation modelingNicotine dependenceInvestigate genetic correlationsADHDPolygenic riskStrength of evidence
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 ResearchMulti-ancestry genome-wide association study of cannabis use disorder yields insight into disease biology and public health implications
Levey D, Galimberti M, Deak J, Wendt F, Bhattacharya A, Koller D, Harrington K, Quaden R, Johnson E, Gupta P, Biradar M, Lam M, Cooke M, Rajagopal V, Empke S, Zhou H, Nunez Y, Kranzler H, Edenberg H, Agrawal A, Smoller J, Lencz T, Hougaard D, Børglum A, Demontis D, Gaziano J, Gandal M, Polimanti R, Stein M, Gelernter J. Multi-ancestry genome-wide association study of cannabis use disorder yields insight into disease biology and public health implications. Nature Genetics 2023, 55: 2094-2103. PMID: 37985822, PMCID: PMC10703690, DOI: 10.1038/s41588-023-01563-z.Peer-Reviewed Original ResearchConceptsSingle nucleotide polymorphism-based heritabilityMulti-ancestry genome-wide association studyAssociation studiesMillion Veteran ProgramGenome-wide association studiesWide significant lociWide association studySignificant lociReference panelSmall populationDisease biologyAncestryAmerican ancestryHeritabilityVeteran ProgramNumerous medical comorbiditiesLung cancer riskRelationship analysisLociBiologyPublic health implicationsEast AsiansPublic health consequencesMedical comorbiditiesCigarette smokingGenome-wide association studies and cross-population meta-analyses investigating short and long sleep duration
Austin-Zimmerman I, Levey D, Giannakopoulou O, Deak J, Galimberti M, Adhikari K, Zhou H, Denaxas S, Irizar H, Kuchenbaecker K, McQuillin A, Concato J, Buysse D, Gaziano J, Gottlieb D, Polimanti R, Stein M, Bramon E, Gelernter J. Genome-wide association studies and cross-population meta-analyses investigating short and long sleep duration. Nature Communications 2023, 14: 6059. PMID: 37770476, PMCID: PMC10539313, DOI: 10.1038/s41467-023-41249-y.Peer-Reviewed Original ResearchConceptsAssociation studiesGenome-wide association studiesGenetic correlationsWide association studyLinkage disequilibrium scorePositive genetic correlationSleep traitsIndependent lociMillion Veteran ProgramTraitsAncestryUK BiobankVeteran ProgramMendelian randomisationLociHeritabilitySNPsPhenotypeEast AsiansSimilar patternCardiometabolic phenotypesIdentifying genetic loci and phenomic associations of substance use traits: A multi‐trait analysis of GWAS (MTAG) study
Xu H, Toikumo S, Crist R, Glogowska K, Jinwala Z, Deak J, Justice A, Gelernter J, Johnson E, Kranzler H, Kember R. Identifying genetic loci and phenomic associations of substance use traits: A multi‐trait analysis of GWAS (MTAG) study. Addiction 2023, 118: 1942-1952. PMID: 37156939, PMCID: PMC10754226, DOI: 10.1111/add.16229.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesSignificant single nucleotide polymorphismsSubstance use traitsMulti-trait analysisAssociation studiesGenetic architectureUse traitsGenome-wide significant single nucleotide polymorphismsProtein-protein interaction analysisTrait genetic architectureNumber of lociPolygenic risk scoresEuropean ancestry individualsNovel lociSingle nucleotide polymorphismsGenetic lociGWAS studiesLociMultiple related phenotypesNucleotide polymorphismsRelated phenotypesTraitsNovel associationsMTAgBiobank samples
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 regressionTraitsUsing Local and Global Genetic Correlation Approaches to Help Elucidate the Shared Genetic Etiology of Psychiatric and Substance Use Traits
Deak J. Using Local and Global Genetic Correlation Approaches to Help Elucidate the Shared Genetic Etiology of Psychiatric and Substance Use Traits. Biological Psychiatry 2022, 92: e31-e33. PMID: 36075672, DOI: 10.1016/j.biopsych.2022.07.011.Peer-Reviewed Original ResearchGenome-wide association study in individuals of European and African ancestry and multi-trait analysis of opioid use disorder identifies 19 independent genome-wide significant risk loci
Deak JD, Zhou H, Galimberti M, Levey DF, Wendt FR, Sanchez-Roige S, Hatoum AS, Johnson EC, Nunez YZ, Demontis D, Børglum AD, Rajagopal VM, Jennings MV, Kember RL, Justice AC, Edenberg HJ, Agrawal A, Polimanti R, Kranzler HR, Gelernter J. Genome-wide association study in individuals of European and African ancestry and multi-trait analysis of opioid use disorder identifies 19 independent genome-wide significant risk loci. Molecular Psychiatry 2022, 27: 3970-3979. PMID: 35879402, PMCID: PMC9718667, DOI: 10.1038/s41380-022-01709-1.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesGenome-wide significant risk lociAssociation studiesVariant associationsLarge-scale genome-wide association studiesGenetic correlationsSignificant risk lociPsychiatric Genomics ConsortiumMulti-trait analysisPolygenic risk score analysisSingle-variant associationsGWS lociGenetic architectureIndividuals of EuropeanGWS associationsRisk lociGene regionGenomics ConsortiumMillion Veteran ProgramSusceptibility lociAfrican ancestryLociRisk score analysisGenetic informativenessSNPs oneUsing phenotype risk scores to enhance gene discovery for generalized anxiety disorder and posttraumatic stress disorder
Wendt FR, Pathak GA, Deak JD, De Angelis F, Koller D, Cabrera-Mendoza B, Lebovitch DS, Levey DF, Stein MB, Kranzler HR, Koenen KC, Gelernter J, Huckins LM, Polimanti R. Using phenotype risk scores to enhance gene discovery for generalized anxiety disorder and posttraumatic stress disorder. Molecular Psychiatry 2022, 27: 2206-2215. PMID: 35181757, PMCID: PMC9133008, DOI: 10.1038/s41380-022-01469-y.Peer-Reviewed Original Research
2021
Alcohol and nicotine polygenic scores are associated with the development of alcohol and nicotine use problems from adolescence to young adulthood
Deak JD, Clark DA, Liu M, Schaefer JD, Jang SK, Durbin CE, Iacono WG, McGue M, Vrieze S, Hicks BM. Alcohol and nicotine polygenic scores are associated with the development of alcohol and nicotine use problems from adolescence to young adulthood. Addiction 2021, 117: 1117-1127. PMID: 34590376, PMCID: PMC8931861, DOI: 10.1111/add.15697.Peer-Reviewed Original ResearchAssociations between polygenic risk of substance use and use disorder and alcohol, cannabis, and nicotine use in adolescence and young adulthood in a longitudinal twin study
Schaefer J, Jang S, Clark D, Deak J, Hicks B, Iacono W, Liu M, McGue M, Vrieze S, Wilson S. Associations between polygenic risk of substance use and use disorder and alcohol, cannabis, and nicotine use in adolescence and young adulthood in a longitudinal twin study. Psychological Medicine 2021, 53: 2296-2306. PMID: 37310313, PMCID: PMC10123833, DOI: 10.1017/s0033291721004116.Peer-Reviewed Original ResearchEffects of genetic risk for alcohol dependence and onset of regular drinking on the progression to alcohol dependence: A polygenic risk score approach
Yeung EW, Spychala KM, Miller AP, Otto JM, Deak JD, Kim H, Gilder DA, Ehlers CL, Wilhelmsen KC, Gizer IR. Effects of genetic risk for alcohol dependence and onset of regular drinking on the progression to alcohol dependence: A polygenic risk score approach. Drug And Alcohol Dependence 2021, 230: 109117. PMID: 34844060, PMCID: PMC8714681, DOI: 10.1016/j.drugalcdep.2021.109117.Peer-Reviewed Original ResearchConceptsRate of progressionRegular drinkingAlcohol dependenceCox proportional hazards regression analysisProportional hazards regression analysisEarly onsetGenetic riskHazards regression analysisHazard of progressionMixed-effects logistic regressionEuropean-ancestry adultsHigh clinical relevanceAD risk variantsEffects logistic regressionAD independentPolygenic risk score approachClinical courseRapid progressionAD preventionFaster progressionPolygenic risk scoresRisk scoreClinical relevanceLate onsetAD diagnosisPolygenic scores for smoking and educational attainment have independent influences on academic success and adjustment in adolescence and educational attainment in adulthood
Hicks B, Clark D, Deak J, Schaefer J, Liu M, Jang S, Durbin C, Johnson W, Wilson S, Iacono W, McGue M, Vrieze S. Polygenic scores for smoking and educational attainment have independent influences on academic success and adjustment in adolescence and educational attainment in adulthood. PLOS ONE 2021, 16: e0255348. PMID: 34403414, PMCID: PMC8370636, DOI: 10.1371/journal.pone.0255348.Peer-Reviewed Original ResearchConceptsEducational attainment polygenic scoreSmoking PGSAcademic adjustmentPolygenic scoresAcademic variablesSignificant incremental associationsAge 14Minnesota Twin Family StudyGenetic influencesGeneral behavioral disinhibitionNon-cognitive traitsEducation polygenic scoreEducational attainmentTwin Family StudyAcademic motivationBehavioral disinhibitionDifferent genetic influencesDistinct genetic influencesPredictors of gradeIncremental associationAcademic successAdolescenceAge 11Educational successAdulthoodThe relationship between cannabis and schizophrenia: a genetically informed perspective
Johnson EC, Hatoum AS, Deak JD, Polimanti R, Murray RM, Edenberg HJ, Gelernter J, Di Forti M, Agrawal A. The relationship between cannabis and schizophrenia: a genetically informed perspective. Addiction 2021, 116: 3227-3234. PMID: 33950550, PMCID: PMC8492483, DOI: 10.1111/add.15534.Peer-Reviewed Original ResearchGenetics of substance use disorders: a review
Deak J, Johnson E. Genetics of substance use disorders: a review. Psychological Medicine 2021, 51: 2189-2200. PMID: 33879270, PMCID: PMC8477224, DOI: 10.1017/s0033291721000969.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesGenome-wide variationAlcohol-related traitsLarger GWAS samplesCHRNB4 gene clusterGenetic architectureGene clusterGenetic effortsGWAS findingsGWA findingsRelated traitsGWAS samplesAssociation studiesGenetic relationshipsDownstream analysisGeneticsTraitsGenetic epidemiologyCHRNA5-CHRNA3Genetic etiologyGenetic factorsGenetic influencesPresent reviewRecent advancesGenes
2019
Effects of Common and Rare Chromosome 4 GABAergic Gene Variation on Alcohol Use and Antisocial Behavior.
Deak J, Gizer I, Otto J, Bizon C, Wilhelmsen K. Effects of Common and Rare Chromosome 4 GABAergic Gene Variation on Alcohol Use and Antisocial Behavior. Journal Of Studies On Alcohol And Drugs 2019, 80: 585-593. PMID: 31790348, PMCID: PMC6900988, DOI: 10.15288/jsad.2019.80.585.Peer-Reviewed Original ResearchConceptsVariant associationsCommon variant associationsRare variant association testsRare variant signalsGene-based analysisRare variant associationsMolecular genetic studiesSingle variant analysisIntergenic regionRare variationAlcohol use disorderTop associationsSequencing dataVariant contributionsGenetic studiesAlcoholism (COGA) sampleGenetic sequencing dataReceptor geneUse disordersVariant signalsGene variationTypes of variationConfer riskStrong associationSignificant associationPolygenic liability for schizophrenia predicts shifting-specific executive function deficits and tobacco use in a moderate drinking community sample
Miller A, Gizer I, Fleming Iii W, Otto J, Deak J, Martins J, Bartholow B. Polygenic liability for schizophrenia predicts shifting-specific executive function deficits and tobacco use in a moderate drinking community sample. Psychiatry Research 2019, 279: 47-54. PMID: 31299563, PMCID: PMC6713597, DOI: 10.1016/j.psychres.2019.06.025.Peer-Reviewed Original Research
2018
Meta‐Analysis of Genetic Influences on Initial Alcohol Sensitivity
Edwards A, Deak J, Gizer I, Lai D, Chatzinakos C, Wilhelmsen K, Lindsay J, Heron J, Hickman M, Webb B, Bacanu S, Foroud T, Kendler K, Dick D, Schuckit M. Meta‐Analysis of Genetic Influences on Initial Alcohol Sensitivity. Alcohol Clinical And Experimental Research 2018, 42: 2349-2359. PMID: 30276832, PMCID: PMC6286211, DOI: 10.1111/acer.13896.Peer-Reviewed Original ResearchConceptsCore clock genesClock genesTissue-specific expression dataPopulation-based genome-wide association studiesGenome-wide association studiesGenome-wide significanceGene identification effortsSignificant genetic correlationsMolecular genetic studiesHormone signalingSingle nucleotide polymorphismsIndividual lociGenetic analysisAssociation studiesGenetic studiesExpression dataGenesGenetic componentGenetic correlationsNucleotide polymorphismsHeritabilityAlcohol sensitivityGenetic factorsLow initial sensitivityGenetic influences