2024
T4. RELATIONSHIP OF GENETICALLY-INDEXED PHYSICAL ACTIVITY WITH MENTAL DISORDERS
Galimberti M, Gupta P, Deak J, Dao C, Nitin R, Zhou H, Harrington K, Na P, Topiwala A, Davis L, Gaziano M, Levey D, Stein M, Gelernter J. T4. RELATIONSHIP OF GENETICALLY-INDEXED PHYSICAL ACTIVITY WITH MENTAL DISORDERS. European Neuropsychopharmacology 2024, 87: 157-158. DOI: 10.1016/j.euroneuro.2024.08.314.Peer-Reviewed Original ResearchProtective effect of PAMental health traitsMillion Veteran ProgramEffects of PAGenome-wide association studiesPhysical activityLocal genetic correlationAlcohol consumptionPosttraumatic stress disorderSmoking initiationLeisure time PARelationship of PAUse disorderMental health outcomesPsychiatric disordersSelf-reported informationSubstance useAttention-deficit/hyperactivity disorderGenetic correlation analysisLocal genetic correlation analysisTime PAGenome-wide association study statisticsHealth traitsMR analysisResults PAGenetic and non-genetic predictors of risk for opioid dependence.
Na P, Deak J, Kranzler H, Pietrzak R, Gelernter J. Genetic and non-genetic predictors of risk for opioid dependence. Psychological Medicine 2024, 54: 1779-1786. PMID: 38317430, PMCID: PMC11132928, DOI: 10.1017/s0033291723003732.Peer-Reviewed Original ResearchPolygenic risk scoresMulti-trait analysis of genome-wide association studyOpioid use disorderPosttraumatic stress disorderPsychosocial/environmental factorsAnalysis of genome-wide association studiesHigher education levelGenome-wide association studiesNon-genetic predictorsEuropean-ancestry adultsEtiology of ODPublic health crisisPsychosocial factorsPolygenic riskMulti-trait analysisEducation levelPsychosocial environmentHousehold incomeRisk scoreAssociation studiesOpioid dependenceDiagnosis of ODLifetime diagnosisYale-PennAssociated with ODGenetic 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 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 smoking8. A CROSS-POPULATION GENOME-WIDE ASSOCIATION STUDY OF SLEEP DURATION
Austin-Zimmerman I, Levey D, Deak J, Galimberti M, Adhikari K, Zhou H, Di Forti M, Polimanti R, Stein M, Gelernter J. 8. A CROSS-POPULATION GENOME-WIDE ASSOCIATION STUDY OF SLEEP DURATION. European Neuropsychopharmacology 2023, 75: s60. DOI: 10.1016/j.euroneuro.2023.08.119.Peer-Reviewed Original ResearchSleep durationMillion Veteran ProgramLong sleepCoronary artery diseaseType 2 diabetesAdequate sleep durationShort sleep durationMajor depressive disorderLong sleep durationSleep duration dataPost-traumatic stress disorderGenome-wide association studiesMendelian randomisation analysisArtery diseaseDisturbed sleepDepressive disorderShort sleepRisk lociHealth outcomesSleep hoursCognitive functionSleepStress disorderRandomisation analysisMendelian randomisation79. A LARGE-SCALE GENOME-WIDE ASSOCIATION STUDY OF COCAINE USE DISORDER
Deak J, Zhou H, Levey D, Galimberti M, Farajzadeh L, Hougaard D, Jennings M, Davis L, Sanchez-Roige S, Demontis D, Børglum A, Kranzler H, Gaziano M, Stein M, Gelernter J. 79. A LARGE-SCALE GENOME-WIDE ASSOCIATION STUDY OF COCAINE USE DISORDER. European Neuropsychopharmacology 2023, 75: s99. DOI: 10.1016/j.euroneuro.2023.08.184.Peer-Reviewed Original ResearchGenome-wide association studiesLarge genome-wide association studiesGWS lociBackground Genome-wide association studiesAssociation studiesLarge-scale genome-wide association studiesTissue expression analysisGenetic architectureGWAS analysisIndividuals of AfricanGWAS discoverySingle locusExpression analysisGenetic dataChromosome 11Silico analysisGenetic discoveriesMillion Veteran ProgramChromosome 13Biological understandingLociEuropean ancestryBiological componentsVeteran ProgramNovel findingsGenome-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 regressionTraitsGenome-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
Genetics 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
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 influencesGenetics of alcohol use disorder: a review
Deak J, Miller A, Gizer I. Genetics of alcohol use disorder: a review. Current Opinion In Psychology 2018, 27: 56-61. PMID: 30170251, PMCID: PMC6368900, DOI: 10.1016/j.copsyc.2018.07.012.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesSuccess of GWASAssociation studiesGenome-wide linkageQuantitative genetic studiesCandidate gene association studiesHundreds of variantsMolecular genetic researchGene association studiesGene discoveryGenetic variationRelevant traitsGWAS dataGenetic studiesGenetic researchEtiology of AUDGenomeTraitsGenetic etiologyHeritabilitySpecific variationsPresent reviewGeneticsRecent effortsSmall effect