2024
Genetic 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 ResearchIdentifying 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 ResearchMeSH KeywordsAgedAlcohol DrinkingAlcoholismFemaleGenome-Wide Association StudyHumansMaleVeteransWhite PeopleConceptsGenome-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 one
2021
Effects 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 diagnosisGenetics 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 association
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 ResearchMeSH KeywordsAlcoholismGenome-Wide Association StudyHumansMolecular BiologyPhenotypePolymorphism, Single NucleotideConceptsGenome-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