Featured Publications
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 ResearchMeSH KeywordsGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMarijuana AbusePolymorphism, Single NucleotidePublic HealthRacial GroupsVeteransConceptsSingle 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 smokingReproducible Genetic Risk Loci for Anxiety: Results From ∼200,000 Participants in the Million Veteran Program
Levey DF, Gelernter J, Polimanti R, Zhou H, Cheng Z, Aslan M, Quaden R, Concato J, Radhakrishnan K, Bryois J, Sullivan PF, Stein M. Reproducible Genetic Risk Loci for Anxiety: Results From ∼200,000 Participants in the Million Veteran Program. American Journal Of Psychiatry 2020, 177: 223-232. PMID: 31906708, PMCID: PMC7869502, DOI: 10.1176/appi.ajp.2019.19030256.Peer-Reviewed Original ResearchMeSH KeywordsAgedAnxietyAnxiety DisordersFemaleGenetic LociGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMaleMiddle AgedPhenotypePolymorphism, Single NucleotideVeteransConceptsNovel genome-wide significant associationsGene expressionGenome-wide significant signalsGenome-wide significant associationMillion Veteran ProgramWide association studyGenetic risk lociSignificant genetic correlationsGenetic risk mechanismsGenetic architectureGlobal regulatorChromosome 3Risk lociChromosome 6Chromosome 7Association studiesLargest GWASLarge biobanksGlobal regulationGenetic correlationsContinuous traitsVeteran ProgramGWASsLociPrevious GWASsGenome-wide association analyses of post-traumatic stress disorder and its symptom subdomains in the Million Veteran Program
Stein MB, Levey DF, Cheng Z, Wendt FR, Harrington K, Pathak GA, Cho K, Quaden R, Radhakrishnan K, Girgenti MJ, Ho YA, Posner D, Aslan M, Duman RS, Zhao H, Polimanti R, Concato J, Gelernter J. Genome-wide association analyses of post-traumatic stress disorder and its symptom subdomains in the Million Veteran Program. Nature Genetics 2021, 53: 174-184. PMID: 33510476, PMCID: PMC7972521, DOI: 10.1038/s41588-020-00767-x.Peer-Reviewed Original ResearchConceptsGenome-wide association analysisAssociation analysisMillion Veteran ProgramGenomic structural equation modelingSignificant lociGenetic varianceGene expressionDrug repositioning candidatesBiological coherenceVeteran ProgramMultiple testing correctionSymptom phenotypeLociRepositioning candidatesAfrican ancestryHeritabilityPhenotypeAncestryExpressionPTSD symptom factorsRegionSubdomainsEnrichmentGenetic associations with suicide attempt severity and genetic overlap with major depression
Levey DF, Polimanti R, Cheng Z, Zhou H, Nuñez YZ, Jain S, He F, Sun X, Ursano RJ, Kessler RC, Smoller JW, Stein MB, Kranzler HR, Gelernter J. Genetic associations with suicide attempt severity and genetic overlap with major depression. Translational Psychiatry 2019, 9: 22. PMID: 30655502, PMCID: PMC6336846, DOI: 10.1038/s41398-018-0340-2.Peer-Reviewed Original ResearchConceptsGWS associationsGenome-wide significant signalsCircadian clock regulationWide association studyGenetic overlapCatabolism of tyrosineClock regulationFirst GWASSignificant genetic overlapDiscovery GWASChromosome 12Large GWASMolecular mechanismsAssociation studiesChromosome 15Chromosome 18Genetic influencesDiscovery sampleGenetic associationSuicide attempt severityReplication analysisGWASAnaerobic energy productionGenetic risk factorsPolygenic risk scoresDepression pathophysiology, risk prediction of recurrence and comorbid psychiatric disorders using genome-wide analyses
Als T, Kurki M, Grove J, Voloudakis G, Therrien K, Tasanko E, Nielsen T, Naamanka J, Veerapen K, Levey D, Bendl J, Bybjerg-Grauholm J, Zeng B, Demontis D, Rosengren A, Athanasiadis G, Bækved-Hansen M, Qvist P, Bragi Walters G, Thorgeirsson T, Stefánsson H, Musliner K, Rajagopal V, Farajzadeh L, Thirstrup J, Vilhjálmsson B, McGrath J, Mattheisen M, Meier S, Agerbo E, Stefánsson K, Nordentoft M, Werge T, Hougaard D, Mortensen P, Stein M, Gelernter J, Hovatta I, Roussos P, Daly M, Mors O, Palotie A, Børglum A. Depression pathophysiology, risk prediction of recurrence and comorbid psychiatric disorders using genome-wide analyses. Nature Medicine 2023, 29: 1832-1844. PMID: 37464041, PMCID: PMC10839245, DOI: 10.1038/s41591-023-02352-1.Peer-Reviewed Original ResearchMeSH KeywordsAttention Deficit Disorder with HyperactivityBipolar DisorderDepressionFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMalePolymorphism, Single NucleotideSchizophreniaConceptsSingle nucleotide polymorphism heritabilityGenome-wide analysisLikely causal genesFunctional genomics dataRisk variantsWide association studyPolygenic burdenPsychiatric disordersCausal genesPolygenic architectureGenomic dataRisk lociAssociation studiesSubgroups of depressionCause of disabilityDepression genetic riskCommon psychiatric disordersPrecision medicine approachCases of depressionOligodendrocyte lineageGenesLociConsiderable sex differencesGABAergic neuronsPsychiatric comorbidityGenome-wide meta-analysis of insomnia prioritizes genes associated with metabolic and psychiatric pathways
Watanabe K, Jansen PR, Savage JE, Nandakumar P, Wang X, Hinds D, Gelernter J, Levey D, Polimanti R, Stein M, Van Someren E, Smit A, Posthuma D. Genome-wide meta-analysis of insomnia prioritizes genes associated with metabolic and psychiatric pathways. Nature Genetics 2022, 54: 1125-1132. PMID: 35835914, DOI: 10.1038/s41588-022-01124-w.Peer-Reviewed Original ResearchMeSH KeywordsBrainGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMultifactorial InheritancePolymorphism, Single NucleotideSleep Initiation and Maintenance DisordersConceptsRisk lociGenome-wide association studiesSpecific gene setsPrevious genome-wide association studyGene prioritization strategyExternal biological resourcesExtreme polygenicityExpression specificityAssociated lociSignaling functionsGene setsAssociation studiesNeuronal differentiationFunctional interactionGenesLociBiological resourcesPolygenicityNovel strategyPrioritization strategiesSpecific hypothesesDifferentiationPathwayStatistical powerLarge number
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 studyParticipantsTraitsGenome-wide association study of the common retinal disorder epiretinal membrane: Significant risk loci in each of three American populations
Gelernter J, Levey D, Galimberti M, Harrington K, Zhou H, Adhikari K, Gupta P, Program V, Gaziano J, Eliott D, Stein M. Genome-wide association study of the common retinal disorder epiretinal membrane: Significant risk loci in each of three American populations. Cell Genomics 2024, 4: 100582. PMID: 38870908, PMCID: PMC11228954, DOI: 10.1016/j.xgen.2024.100582.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesMillion Veteran ProgramRisk lociAssociation studiesTrans-ancestry meta-analysisSignificant risk lociPathway enrichment analysisEpiretinal membraneTrans-ancestryGenome-wideMultiple traitsGenetic associationEnrichment analysisGene expressionEuropean AmericansLoss of visual acuityVeteran ProgramGenetic correlationsLociBiological mechanismsAmerican populationVisual acuityRetinal conditionsControl individualsRetinal surfaceGenome-wide association analyses identify 95 risk loci and provide insights into the neurobiology of post-traumatic stress disorder
Nievergelt C, Maihofer A, Atkinson E, Chen C, Choi K, Coleman J, Daskalakis N, Duncan L, Polimanti R, Aaronson C, Amstadter A, Andersen S, Andreassen O, Arbisi P, Ashley-Koch A, Austin S, Avdibegoviç E, Babić D, Bacanu S, Baker D, Batzler A, Beckham J, Belangero S, Benjet C, Bergner C, Bierer L, Biernacka J, Bierut L, Bisson J, Boks M, Bolger E, Brandolino A, Breen G, Bressan R, Bryant R, Bustamante A, Bybjerg-Grauholm J, Bækvad-Hansen M, Børglum A, Børte S, Cahn L, Calabrese J, Caldas-de-Almeida J, Chatzinakos C, Cheema S, Clouston S, Colodro-Conde L, Coombes B, Cruz-Fuentes C, Dale A, Dalvie S, Davis L, Deckert J, Delahanty D, Dennis M, Desarnaud F, DiPietro C, Disner S, Docherty A, Domschke K, Dyb G, Kulenović A, Edenberg H, Evans A, Fabbri C, Fani N, Farrer L, Feder A, Feeny N, Flory J, Forbes D, Franz C, Galea S, Garrett M, Gelaye B, Gelernter J, Geuze E, Gillespie C, Goleva S, Gordon S, Goçi A, Grasser L, Guindalini C, Haas M, Hagenaars S, Hauser M, Heath A, Hemmings S, Hesselbrock V, Hickie I, Hogan K, Hougaard D, Huang H, Huckins L, Hveem K, Jakovljević M, Javanbakht A, Jenkins G, Johnson J, Jones I, Jovanovic T, Karstoft K, Kaufman M, Kennedy J, Kessler R, Khan A, Kimbrel N, King A, Koen N, Kotov R, Kranzler H, Krebs K, Kremen W, Kuan P, Lawford B, Lebois L, Lehto K, Levey D, Lewis C, Liberzon I, Linnstaedt S, Logue M, Lori A, Lu Y, Luft B, Lupton M, Luykx J, Makotkine I, Maples-Keller J, Marchese S, Marmar C, Martin N, Martínez-Levy G, McAloney K, McFarlane A, McLaughlin K, McLean S, Medland S, Mehta D, Meyers J, Michopoulos V, Mikita E, Milani L, Milberg W, Miller M, Morey R, Morris C, Mors O, Mortensen P, Mufford M, Nelson E, Nordentoft M, Norman S, Nugent N, O’Donnell M, Orcutt H, Pan P, Panizzon M, Pathak G, Peters E, Peterson A, Peverill M, Pietrzak R, Polusny M, Porjesz B, Powers A, Qin X, Ratanatharathorn A, Risbrough V, Roberts A, Rothbaum A, Rothbaum B, Roy-Byrne P, Ruggiero K, Rung A, Runz H, Rutten B, de Viteri S, Salum G, Sampson L, Sanchez S, Santoro M, Seah C, Seedat S, Seng J, Shabalin A, Sheerin C, Silove D, Smith A, Smoller J, Sponheim S, Stein D, Stensland S, Stevens J, Sumner J, Teicher M, Thompson W, Tiwari A, Trapido E, Uddin M, Ursano R, Valdimarsdóttir U, Van Hooff M, Vermetten E, Vinkers C, Voisey J, Wang Y, Wang Z, Waszczuk M, Weber H, Wendt F, Werge T, Williams M, Williamson D, Winsvold B, Winternitz S, Wolf C, Wolf E, Xia Y, Xiong Y, Yehuda R, Young K, Young R, Zai C, Zai G, Zervas M, Zhao H, Zoellner L, Zwart J, deRoon-Cassini T, van Rooij S, van den Heuvel L, Stein M, Ressler K, Koenen K. Genome-wide association analyses identify 95 risk loci and provide insights into the neurobiology of post-traumatic stress disorder. Nature Genetics 2024, 56: 792-808. PMID: 38637617, PMCID: PMC11396662, DOI: 10.1038/s41588-024-01707-9.Peer-Reviewed Original ResearchMeSH KeywordsGenetic LociGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansNeurobiologyPolymorphism, Single NucleotideStress Disorders, Post-TraumaticWhite PeopleConceptsMeta-analysis of genome-wide association studiesGenome-wide significant lociMulti-ancestry meta-analysisGenome-wide association analysisGenome-wide association studiesIndividuals of European ancestryPotential causal genesNative American ancestryMulti-omics approachPost-traumatic stress disorderAdmixed individualsSignificant lociRisk lociCausal genesAssociation studiesAssociation analysisFunctional genesTranscription factorsGenetic studiesAmerican ancestryEuropean ancestryAxon guidanceSynaptic structureLociGenes
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 ResearchAlcoholismGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansPhenotypePolymorphism, Single NucleotideRacial GroupsGenome-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 ResearchMeSH KeywordsAdultGenome-Wide Association StudyHumansMendelian Randomization AnalysisPhenotypePolymorphism, Single NucleotideSleepSleep DurationConceptsAssociation studiesGenome-wide association studiesGenetic correlationsWide association studyLinkage disequilibrium scorePositive genetic correlationSleep traitsIndependent lociMillion Veteran ProgramTraitsAncestryUK BiobankVeteran ProgramMendelian randomisationLociHeritabilitySNPsPhenotypeEast AsiansSimilar patternCardiometabolic phenotypesModeling the longitudinal changes of ancestry diversity in the Million Veteran Program
Wendt F, Pathak G, Vahey J, Qin X, Koller D, Cabrera-Mendoza B, Haeny A, Harrington K, Rajeevan N, Duong L, Levey D, De Angelis F, De Lillo A, Bigdeli T, Pyarajan S, Gaziano J, Gelernter J, Aslan M, Provenzale D, Helmer D, Hauser E, Polimanti R. Modeling the longitudinal changes of ancestry diversity in the Million Veteran Program. Human Genomics 2023, 17: 46. PMID: 37268996, PMCID: PMC10239111, DOI: 10.1186/s40246-023-00487-3.Peer-Reviewed Original Research
2022
Genetic variants associated with psychiatric disorders are enriched at epigenetically active sites in lymphoid cells
Lynall ME, Soskic B, Hayhurst J, Schwartzentruber J, Levey DF, Pathak GA, Polimanti R, Gelernter J, Stein MB, Trynka G, Clatworthy MR, Bullmore E. Genetic variants associated with psychiatric disorders are enriched at epigenetically active sites in lymphoid cells. Nature Communications 2022, 13: 6102. PMID: 36243721, PMCID: PMC9569335, DOI: 10.1038/s41467-022-33885-7.Peer-Reviewed Original ResearchMeSH KeywordsCatalytic DomainGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansLymphocytesMental DisordersPolymorphism, Single NucleotideSchizophreniaConceptsMultiple psychiatric disordersPsychiatric disordersPsychiatric risk variantT cellsLymphoid cellsRisk variantsImmune cell subsetsMental health disordersMultiple organ systemsAdaptive immune systemCell subsetsImmune cellsHealth disordersMyeloid cellsImmune systemBrain tissueOrgan systemsSpecific disordersDisordersPathogenesisAbnormalitiesGenetic variantsCellsCD4VariantsUnderstanding the comorbidity between posttraumatic stress severity and coronary artery disease using genome-wide information and electronic health records
Polimanti R, Wendt FR, Pathak GA, Tylee DS, Tcheandjieu C, Hilliard AT, Levey DF, Adhikari K, Gaziano JM, O’Donnell C, Assimes TL, Stein MB, Gelernter J. Understanding the comorbidity between posttraumatic stress severity and coronary artery disease using genome-wide information and electronic health records. Molecular Psychiatry 2022, 27: 3961-3969. PMID: 35986173, PMCID: PMC10986859, DOI: 10.1038/s41380-022-01735-z.Peer-Reviewed Original ResearchMeSH KeywordsComorbidityCoronary Artery DiseaseElectronic Health RecordsGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansPolymorphism, Single NucleotideRisk FactorsStress Disorders, Post-TraumaticConceptsCoronary artery diseasePosttraumatic stress disorderElectronic health recordsMillion Veteran ProgramArtery diseaseTotal scoreCAD diagnosisPlatelet amyloid precursor proteinHealth recordsPosttraumatic stress severityAmyloid precursor proteinEarly CAD diagnosisUK BiobankBidirectional relationshipTwo-sample Mendelian randomization (MR) analysisMendelian randomization analysisCAD riskHigh morbidityPTSD symptom severityCARDIoGRAMplusC4D consortiumPleiotropic mechanismsSymptom severityLongitudinal changesDiscordant effectsStress disorderAlcohol consumption and telomere length: Mendelian randomization clarifies alcohol’s effects
Topiwala A, Taschler B, Ebmeier KP, Smith S, Zhou H, Levey DF, Codd V, Samani NJ, Gelernter J, Nichols TE, Burgess S. Alcohol consumption and telomere length: Mendelian randomization clarifies alcohol’s effects. Molecular Psychiatry 2022, 27: 4001-4008. PMID: 35879401, PMCID: PMC9718662, DOI: 10.1038/s41380-022-01690-9.Peer-Reviewed Original ResearchAlcohol DrinkingEthanolGenome-Wide Association StudyHumansMendelian Randomization AnalysisPolymorphism, Single NucleotideTelomereGenome-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 ResearchMeSH KeywordsAlcoholismBlack PeopleFurinGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansOpioid-Related DisordersPhenotypePolymorphism, Single NucleotideWhite PeopleConceptsGenome-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 oneAn Atlas of Genetic Correlations and Genetically Informed Associations Linking Psychiatric and Immune-Related Phenotypes
Tylee DS, Lee YK, Wendt FR, Pathak GA, Levey DF, De Angelis F, Gelernter J, Polimanti R. An Atlas of Genetic Correlations and Genetically Informed Associations Linking Psychiatric and Immune-Related Phenotypes. JAMA Psychiatry 2022, 79: 667-676. PMID: 35507366, PMCID: PMC9069342, DOI: 10.1001/jamapsychiatry.2022.0914.Peer-Reviewed Original ResearchMeSH KeywordsAsthmaColitis, UlcerativeCrohn DiseaseGenome-Wide Association StudyHumansPhenotypePolymorphism, Single NucleotideRhinitis, AllergicConceptsRisk factorsImmune-related phenotypesMultivariable adjustmentUlcerative colitisCrohn's diseaseMendelian randomizationImmune-related disordersReciprocal risk factorsHealth-related behaviorsPsychiatric phenotypesFalse discovery rate correctionAllergic rhinitisGenetic association studiesGenetic associationInflammatory disordersClinical associationsMajor depressionImmune disordersMAIN OUTCOMEPsychiatric disordersSocial determinantsDisordersAssociation studiesColitisAsthmaIntegrating human brain proteomes with genome-wide association data implicates novel proteins in post-traumatic stress disorder
Wingo TS, Gerasimov ES, Liu Y, Duong DM, Vattathil SM, Lori A, Gockley J, Breen MS, Maihofer AX, Nievergelt CM, Koenen KC, Levey DF, Gelernter J, Stein MB, Ressler KJ, Bennett DA, Levey AI, Seyfried NT, Wingo AP. Integrating human brain proteomes with genome-wide association data implicates novel proteins in post-traumatic stress disorder. Molecular Psychiatry 2022, 27: 3075-3084. PMID: 35449297, PMCID: PMC9233006, DOI: 10.1038/s41380-022-01544-4.Peer-Reviewed Original ResearchMeSH KeywordsBrainGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansPolymorphism, Single NucleotideProteomeStress Disorders, Post-TraumaticTranscriptomeVeteransConceptsProteome-wide association studyTranscriptome-wide association studyGenome-wide association studiesBrain protein abundanceHuman brain proteomeBrain proteomeAssociation studiesProtein abundanceGenome-wide association dataHuman brain transcriptomePost-traumatic stress disorderGWAS resultsNovel proteinBrain transcriptomeRisk lociProteomeGenesAssociation dataPrecursor cellsPTSD pathogenesisBrain mRNA levelsMRNA levelsOligodendrocyte precursor cellsPromising targetNew insights
2021
Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors
Mullins N, Kang J, Campos AI, Coleman JRI, Edwards AC, Galfalvy H, Levey DF, Lori A, Shabalin A, Starnawska A, Su MH, Watson HJ, Adams M, Awasthi S, Gandal M, Hafferty JD, Hishimoto A, Kim M, Okazaki S, Otsuka I, Ripke S, Ware EB, Bergen AW, Berrettini WH, Bohus M, Brandt H, Chang X, Chen WJ, Chen HC, Crawford S, Crow S, DiBlasi E, Duriez P, Fernández-Aranda F, Fichter MM, Gallinger S, Glatt SJ, Gorwood P, Guo Y, Hakonarson H, Halmi KA, Hwu HG, Jain S, Jamain S, Jiménez-Murcia S, Johnson C, Kaplan AS, Kaye WH, Keel PK, Kennedy JL, Klump KL, Li D, Liao SC, Lieb K, Lilenfeld L, Liu CM, Magistretti PJ, Marshall CR, Mitchell JE, Monson ET, Myers RM, Pinto D, Powers A, Ramoz N, Roepke S, Rozanov V, Scherer SW, Schmahl C, Sokolowski M, Strober M, Thornton LM, Treasure J, Tsuang MT, Witt SH, Woodside DB, Yilmaz Z, Zillich L, Adolfsson R, Agartz I, Air TM, Alda M, Alfredsson L, Andreassen OA, Anjorin A, Appadurai V, Artigas M, Van der Auwera S, Azevedo MH, Bass N, Bau CHD, Baune BT, Bellivier F, Berger K, Biernacka JM, Bigdeli TB, Binder EB, Boehnke M, Boks MP, Bosch R, Braff DL, Bryant R, Budde M, Byrne EM, Cahn W, Casas M, Castelao E, Cervilla JA, Chaumette B, Cichon S, Corvin A, Craddock N, Craig D, Degenhardt F, Djurovic S, Edenberg HJ, Fanous AH, Foo JC, Forstner AJ, Frye M, Fullerton JM, Gatt JM, Gejman PV, Giegling I, Grabe HJ, Green MJ, Grevet EH, Grigoroiu-Serbanescu M, Gutierrez B, Guzman-Parra J, Hamilton SP, Hamshere ML, Hartmann A, Hauser J, Heilmann-Heimbach S, Hoffmann P, Ising M, Jones I, Jones LA, Jonsson L, Kahn RS, Kelsoe JR, Kendler KS, Kloiber S, Koenen KC, Kogevinas M, Konte B, Krebs MO, Landén M, Lawrence J, Leboyer M, Lee PH, Levinson DF, Liao C, Lissowska J, Lucae S, Mayoral F, McElroy SL, McGrath P, McGuffin P, McQuillin A, Medland SE, Mehta D, Melle I, Milaneschi Y, Mitchell PB, Molina E, Morken G, Mortensen PB, Müller-Myhsok B, Nievergelt C, Nimgaonkar V, Nöthen MM, O’Donovan M, Ophoff RA, Owen MJ, Pato C, Pato MT, Penninx BWJH, Pimm J, Pistis G, Potash JB, Power RA, Preisig M, Quested D, Ramos-Quiroga JA, Reif A, Ribasés M, Richarte V, Rietschel M, Rivera M, Roberts A, Roberts G, Rouleau GA, Rovaris DL, Rujescu D, Sánchez-Mora C, Sanders AR, Schofield PR, Schulze TG, Scott LJ, Serretti A, Shi J, Shyn SI, Sirignano L, Sklar P, Smeland OB, Smoller JW, Sonuga-Barke EJS, Spalletta G, Strauss JS, Świątkowska B, Trzaskowski M, Turecki G, Vilar-Ribó L, Vincent JB, Völzke H, Walters JTR, Weickert C, Weickert TW, Weissman MM, Williams LM, Wray NR, Zai CC, Ashley-Koch AE, Beckham JC, Hauser ER, Hauser MA, Kimbrel NA, Lindquist JH, McMahon B, Oslin DW, Qin X, Agerbo E, Børglum A, Breen G, Erlangsen A, Esko T, Gelernter J, Hougaard D, Kessler R, Kranzler H, Li Y, Martin N, McIntosh A, Mors O, Nordentoft M, Olsen C, Porteous D, Ursano R, Wasserman D, Werge T, Whiteman D, Bulik C, Coon H, Demontis D, Docherty A, Kuo P, Lewis G, Mann J, Rentería M, Smith D, Stahl E, Stein D, Streit F, Willour V, Ruderfer D, Wray N, Ripke S, Mattheisen M, Trzaskowski M, Byrne E, Abdellaoui A, Adams M, Agerbo E, Air T, Andlauer T, Bacanu S, Bækvad-Hansen M, Beekman A, Bigdeli T, Binder E, Bryois J, Buttenschøn H, Bybjerg-Grauholm J, Cai N, Castelao E, Christensen J, Clarke T, Coleman J, Colodro-Conde L, Couvy-Duchesne B, Craddock N, Crawford G, Davies G, Degenhardt F, Derks E, Direk N, Dolan C, Dunn E, Eley T, Escott-Price V, Kiadeh F, Finucane H, Foo J, Forstner A, Frank J, Gaspar H, Gill M, Goes F, Gordon S, Weinsheimer S, Wellmann J, Willemsen G, Witt S, Wu Y, Xi H, Yang J, Zhang F, Arolt V, Baune B, Berger K, Boomsma D, Cichon S, Dannlowski U, de Geus E, Depaulo J, Domenici E, Domschke K, Esko T, Grabe H, Hamilton S, Grove J, Hall L, Hansen C, Hansen T, Herms S, Hickie I, Hoffmann P, Homuth G, Horn C, Hottenga J, Hougaard D, Howard D, Ising M, Jansen R, Jones I, Jones L, Jorgenson E, Knowles J, Kohane I, Kraft J, Kretzschmar W, Kutalik Z, Li Q, Lind P, MacIntyre D, MacKinnon D, Maier R, Maier W, Marchini J, Mbarek H, McGrath P, 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Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors. Biological Psychiatry 2021, 91: 313-327. PMID: 34861974, PMCID: PMC8851871, DOI: 10.1016/j.biopsych.2021.05.029.Peer-Reviewed Original ResearchMeSH KeywordsDepressive Disorder, MajorGenome-Wide Association StudyHumansMental DisordersPolymorphism, Single NucleotideRisk FactorsSuicide, AttemptedConceptsGenome-wide association studiesGenetic architecturePsychiatric disordersGenetic correlationsRisk factorsGenome-wide significanceDivergent genetic architecturesGWAS summary statisticsShared genetic architectureStrong genetic correlationIntergenic lociSuicide attemptsReproductive traitsKnown Risk FactorsRisk lociPoor general healthChromosome 7Association studiesRelated psychiatric disordersMillion Veteran ProgramSuicide attempt casesLow socioeconomic statusLociNonfatal suicide attemptsGenetic effectsPleiotropic effects of telomere length loci with brain morphology and brain tissue expression
Pathak GA, Wendt FR, Levey DF, Mecca AP, van Dyck CH, Gelernter J, Polimanti R. Pleiotropic effects of telomere length loci with brain morphology and brain tissue expression. Human Molecular Genetics 2021, 30: 1360-1370. PMID: 33831179, PMCID: PMC8255129, DOI: 10.1093/hmg/ddab102.Peer-Reviewed Original ResearchMeSH KeywordsBrainGenome-Wide Association StudyLeukocytesPolymorphism, Single NucleotideTelomereTelomere HomeostasisConceptsMethylation expressionGenetic variantsMapping gene functionTelomere lengthChromatin associationChromatin profilesGene functionGenetic colocalizationGene mappingGenomic relationshipsNeuropsychiatric traitsPleiotropic rolesDrug-gene interactionsCertain lociBrain tissue expressionGenesLociPleiotropic effectsBrain morphology measuresNucleotide polymorphismsAncestry populationsTissue expressionPhenotypic associationsPleiotropyAncestry groups