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 PAF96. ALCOHOL USE AND DEMENTIA IN DIVERSE POPULATIONS
Topiwala A, Levey D, Zhou H, Deak J, Adhikari K, Ebmeier K, Bell S, Burgess S, Nichols T, Gaziano M, Stein M, Gelernter J. F96. ALCOHOL USE AND DEMENTIA IN DIVERSE POPULATIONS. European Neuropsychopharmacology 2024, 87: 256-257. DOI: 10.1016/j.euroneuro.2024.08.507.Peer-Reviewed Original ResearchMillion Veteran ProgramDementia riskMendelian randomizationDementia casesAlcohol usePrevalence of alcohol use disordersImpact of alcohol useRandom-effects meta-analysisAlcohol use disorder prevalenceProspective cohort studyStandard deviation increaseObservational associationsUK BiobankVeteran ProgramLevels of drinkingPopulation prevalenceAlcohol consumptionAlcohol use disorderCohort studyDisorder prevalenceDementiaDependent drinkersDose-response relationshipGenetic associationLight drinkersDiversity 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 studyParticipantsTraitsPleiotropy and genetically inferred causality linking multisite chronic pain to substance use disorders
Koller D, Friligkou E, Stiltner B, Pathak G, Løkhammer S, Levey D, Zhou H, Hatoum A, Deak J, Kember R, Treur J, Kranzler H, Johnson E, Stein M, Gelernter J, Polimanti R. Pleiotropy and genetically inferred causality linking multisite chronic pain to substance use disorders. Molecular Psychiatry 2024, 29: 2021-2030. PMID: 38355787, PMCID: PMC11324857, DOI: 10.1038/s41380-024-02446-3.Peer-Reviewed Original ResearchMultisite chronic painSubstance use disordersChronic painUK BiobankUse disorderMillion Veteran ProgramSNP-based heritabilityGenome-wide association statisticsMR analysisPotential causal relationshipVeteran ProgramPleiotropy analysisTobacco usePleiotropic variantsOpioid use disorderAssociation statisticsCannabis use disorderAlcohol use disorderMeta-analysesBrain-wide analysisImaging phenotypesBi-directional relationshipPainPleiotropyBiobank
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 smokingT18. 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 development8. 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 phenotypes
2022
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
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