2024
Diversity 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 studyParticipantsTraits
2023
Genome-wide analyses reveal shared genetic architecture and novel risk loci between opioid use disorder and general cognitive ability
Holen B, Kutrolli G, Shadrin A, Icick R, Hindley G, Rødevand L, O'Connell K, Frei O, Parker N, Tesfaye M, Deak J, Jahołkowski P, Dale A, Djurovic S, Andreassen O, Smeland O. Genome-wide analyses reveal shared genetic architecture and novel risk loci between opioid use disorder and general cognitive ability. Drug And Alcohol Dependence 2023, 256: 111058. PMID: 38244365, DOI: 10.1016/j.drugalcdep.2023.111058.Peer-Reviewed Original ResearchGenetic basisBivariate causal mixture modelRisk lociGenome-wide analysisNovel risk lociNegative genetic correlationSpecific genetic lociUnderlying molecular mechanismsGenetic risk architectureSpecific genetic variantsGenetic architectureGenetic lociBiological functionsMolecular mechanismsGenetic relationshipsLociGenetic correlationsGenetic variantsGenetic overlapRisk architectureConjunctional FDRNew insightsRecent studiesBiological substratesGenesT18. GENETIC CONTRIBUTION TO THE COMORBIDITY BETWEEN ATTENTION-DEFICIT HYPERACTIVITY DISORDER AND SUBSTANCE USE DISORDERS
Koller D, Mitjans M, Kouakou M, Friligkou E, Mendoza B, Deak J, Pathak G, Kranzler H, Agrawal A, Corominas R, Demontis D, Gelernter J, Ribases M, Cormand B, Polimanti R. T18. GENETIC CONTRIBUTION TO THE COMORBIDITY BETWEEN ATTENTION-DEFICIT HYPERACTIVITY DISORDER AND SUBSTANCE USE DISORDERS. European Neuropsychopharmacology 2023, 75: s171. DOI: 10.1016/j.euroneuro.2023.08.306.Peer-Reviewed Original ResearchGenome-wide association statisticsPleiotropy analysisLinkage disequilibrium score regressionPairwise genetic correlationsGenetic correlation analysisDisequilibrium score regressionProblematic tobacco usePsychiatric Genomics ConsortiumGenetic architectureGenomic SEMGenetic mechanismsGenomics ConsortiumPathogenic lociPleiotropic variantsGenetic relationshipsMillion Veteran ProgramGenetic correlationsScore regressionGenetic contributionAssociation statisticsMolecular targetsBidirectional Mendelian randomization analysisEnvironmental factorsGenetic factorsDrug development79. 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 findingsIdentifying 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 one
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