2023
Genome-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 phenotypesMulti‐omics cannot replace sample size in genome‐wide association studies
Baranger D, Hatoum A, Polimanti R, Gelernter J, Edenberg H, Bogdan R, Agrawal A. Multi‐omics cannot replace sample size in genome‐wide association studies. Genes Brain & Behavior 2023, 22: e12846. PMID: 36977197, PMCID: PMC10733567, DOI: 10.1111/gbb.12846.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesLarge genome-wide association studiesNovel genesMulti-omics dataMulti-omics informationAssociation studiesGenome-wide significant lociSmall genome-wide association studyBrain-related traitsGWAS sample sizesEarly genome-wide association studiesNovel gene discoveryGene discoverySignificant lociAdditional genesPositional mappingHeritable traitVariant discoverySimilar traitsGenesNovel variant discoveryTraitsDisease biologyLociDiscoveryFunctional and molecular characterization of suicidality factors using phenotypic and genome-wide data
Quintero Reis A, Newton B, Kessler R, Polimanti R, Wendt F. Functional and molecular characterization of suicidality factors using phenotypic and genome-wide data. Molecular Psychiatry 2023, 28: 1064-1071. PMID: 36604601, PMCID: PMC10005939, DOI: 10.1038/s41380-022-01929-5.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesPolygenic scoringSummary association dataGenome-wide dataSNP effect sizesGenomic structural equation modelingGenetic study designsNew traitsAdmixed AmericansEffect size distributionBiological pathwaysAssociation studiesTranscriptomic featuresMolecular characterizationSusceptibility lociGenetic correlationsAssociation dataWide dataTraitsGenetic contributionEuropean ancestryCommon genetic factorsLociPhenotypeGenetic factors
2022
Genetically regulated multi-omics study for symptom clusters of posttraumatic stress disorder highlights pleiotropy with hematologic and cardio-metabolic traits
Pathak GA, Singh K, Wendt FR, Fleming TW, Overstreet C, Koller D, Tylee DS, De Angelis F, Cabrera Mendoza B, Levey DF, Koenen KC, Krystal JH, Pietrzak RH, O’ Donell C, Gaziano JM, Falcone G, Stein MB, Gelernter J, Pasaniuc B, Mancuso N, Davis LK, Polimanti R. Genetically regulated multi-omics study for symptom clusters of posttraumatic stress disorder highlights pleiotropy with hematologic and cardio-metabolic traits. Molecular Psychiatry 2022, 27: 1394-1404. PMID: 35241783, PMCID: PMC9210390, DOI: 10.1038/s41380-022-01488-9.Peer-Reviewed Original ResearchConceptsLocal genetic correlationsCell type-specific expressionVanderbilt University biorepositoryMulti-omics studiesMulti-omics investigationsDorsolateral prefrontal cortex tissueGenomic evidenceLaboratory traitsSpecific expressionCardio-metabolic traitsMillion Veteran ProgramPrefrontal cortex tissueMiR-148GenesGenetic correlationsRegulatory profileTraitsProtein expressionCardiometabolic traitsExpressionVeteran ProgramCortex tissueBiological heterogeneitySplicingPrioritization approachUsing 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
Cross-ancestry genome-wide association studies identified heterogeneous loci associated with differences of allele frequency and regulome tagging between participants of European descent and other ancestry groups from the UK Biobank
De Lillo A, D'Antona S, Pathak GA, Wendt FR, De Angelis F, Fuciarelli M, Polimanti R. Cross-ancestry genome-wide association studies identified heterogeneous loci associated with differences of allele frequency and regulome tagging between participants of European descent and other ancestry groups from the UK Biobank. Human Molecular Genetics 2021, 30: 1457-1467. PMID: 33890984, PMCID: PMC8283210, DOI: 10.1093/hmg/ddab114.Peer-Reviewed Original ResearchConceptsGWS associationsHeterogeneous lociGenome-wide association studiesEuropean populationsAncestry-specific effectsAllele frequenciesWide significant associationsPhenome-wide analysisAncestry groupsComplex traitsLD variationPhenotypic classesAssociation studiesUK BiobankMapping variantsLociConcordant effectsCentral/South AsianAncestryWorldwide populationTraitsAsian ancestryDiscordant effectsSouth Asian ancestryEuropean descentPosttraumatic stress disorder: from gene discovery to disease biology
Polimanti R, Wendt FR. Posttraumatic stress disorder: from gene discovery to disease biology. Psychological Medicine 2021, 51: 2178-2188. PMID: 33583458, PMCID: PMC8364573, DOI: 10.1017/s0033291721000210.Peer-Reviewed Original ResearchConceptsGenome-wide associationEpigenome-wide associationComplex traitsGene discoveryAncestral diversityMorphological similarityHeritable riskDisease biologyDiverse numberBiologyWide arrayTranscriptomicsCertain traumatic eventsTraitsDiversityComplex mental disorderHighest conditional riskPopulationFuture studiesDiscovery
2020
Characterizing the effect of background selection on the polygenicity of brain-related traits
Wendt FR, Pathak GA, Overstreet C, Tylee DS, Gelernter J, Atkinson EG, Polimanti R. Characterizing the effect of background selection on the polygenicity of brain-related traits. Genomics 2020, 113: 111-119. PMID: 33278486, PMCID: PMC7855394, DOI: 10.1016/j.ygeno.2020.11.032.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesBrain-related traitsGWAS of schizophreniaTrait-associated lociLocus effect sizesSubset of traitsGenotype networksGenetic architectureIntolerant regionsBrain-related phenotypesBackground selectionNatural selectionEvolutionary pressurePositive selectionSNP heritabilityLocal ancestryAssociation studiesTraitsFunctional significanceLociPolygenicityBinary annotationPhenotypeRisk allelesSize varianceGenome-wide meta-analysis of problematic alcohol use in 435,563 individuals yields insights into biology and relationships with other traits
Zhou H, Sealock JM, Sanchez-Roige S, Clarke TK, Levey DF, Cheng Z, Li B, Polimanti R, Kember RL, Smith RV, Thygesen JH, Morgan MY, Atkinson SR, Thursz MR, Nyegaard M, Mattheisen M, Børglum AD, Johnson EC, Justice AC, Palmer AA, McQuillin A, Davis LK, Edenberg HJ, Agrawal A, Kranzler HR, Gelernter J. Genome-wide meta-analysis of problematic alcohol use in 435,563 individuals yields insights into biology and relationships with other traits. Nature Neuroscience 2020, 23: 809-818. PMID: 32451486, PMCID: PMC7485556, DOI: 10.1038/s41593-020-0643-5.Peer-Reviewed Original ResearchConceptsRegulatory genomic regionsGenome-wide association studiesNovel risk lociEuropean ancestry individualsPolygenic risk score analysisIndependent risk variantsGenetic architectureGenomic regionsRisk lociAssociation studiesGenetic relationshipsRisk genesGenetic correlationsPsychiatric traitsRisk variantsRisk score analysisTraitsGenetic heritabilityYields insightsBiobank samplesMendelian randomizationGenesLociBiologyHeritability
2019
Genome-wide association study of alcohol consumption and use disorder in 274,424 individuals from multiple populations
Kranzler HR, Zhou H, Kember RL, Vickers Smith R, Justice AC, Damrauer S, Tsao PS, Klarin D, Baras A, Reid J, Overton J, Rader DJ, Cheng Z, Tate JP, Becker WC, Concato J, Xu K, Polimanti R, Zhao H, Gelernter J. Genome-wide association study of alcohol consumption and use disorder in 274,424 individuals from multiple populations. Nature Communications 2019, 10: 1499. PMID: 30940813, PMCID: PMC6445072, DOI: 10.1038/s41467-019-09480-8.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesAssociation studiesMillion Veteran Program sampleGenetic correlationsWide significant lociSignificant genetic correlationsPolygenic risk scoresCell type groupSignificant lociHeritable traitEnrichment analysisTraitsMultiple populationsLociPhenotypeProgram samples
2018
Local adaptation in European populations affected the genetics of psychiatric disorders and behavioral traits
Polimanti R, Kayser MH, Gelernter J. Local adaptation in European populations affected the genetics of psychiatric disorders and behavioral traits. Genome Medicine 2018, 10: 24. PMID: 29580271, PMCID: PMC5870256, DOI: 10.1186/s13073-018-0532-7.Peer-Reviewed Original ResearchConceptsLocal adaptationPathogen diversityEuropean populationsBehavioral traitsGenome-wide investigationGenome-wide dataPolygenic risk score analysisProtozoan diversityWinter minimum temperaturesGenetic diversityEvolutionary mechanismsPositive selectionWidespread signalMolecular mechanismsTop findingsRisk score analysisDiversityTraitsCommon variationBehavioral phenotypesAdaptationGeneticsPopulationPhenotypeMechanism
2017
Genetic Risk Variants Associated With Comorbid Alcohol Dependence and Major Depression
Zhou H, Polimanti R, Yang BZ, Wang Q, Han S, Sherva R, Nuñez YZ, Zhao H, Farrer LA, Kranzler HR, Gelernter J. Genetic Risk Variants Associated With Comorbid Alcohol Dependence and Major Depression. JAMA Psychiatry 2017, 74: 1234-1241. PMID: 29071344, PMCID: PMC6331050, DOI: 10.1001/jamapsychiatry.2017.3275.Peer-Reviewed Original ResearchMeSH KeywordsAdultAlcoholismBlack or African AmericanComorbidityDepressive Disorder, MajorDiagnostic and Statistical Manual of Mental DisordersFemaleGenetic Predisposition to DiseaseGenetic VariationHumansMaleMiddle AgedMultifactorial InheritanceOrgan SizePutamenSemaphorin-3AUnited StatesWhite PeopleConceptsGenome-wide association studiesGenetic risk variantsNeuropsychiatric traitsAssociation studiesRisk variantsPolygenic risk allelesPolygenic risk scoresGenetic mechanismsGenetic basisAmerican data setMolecular natureTraitsCriterion countsGenetic causePossible genetic causesMD comorbidityRisk allelesComorbid alcohol dependenceA putative causal relationship between genetically determined female body shape and posttraumatic stress disorder
Polimanti R, Amstadter AB, Stein MB, Almli LM, Baker DG, Bierut LJ, Bradley B, Farrer LA, Johnson EO, King A, Kranzler HR, Maihofer AX, Rice JP, Roberts AL, Saccone NL, Zhao H, Liberzon I, Ressler KJ, Nievergelt CM, Koenen KC, Gelernter J, for The Psychiatric Genomics Consortium Posttraumatic Stress Disorder Workgroup. A putative causal relationship between genetically determined female body shape and posttraumatic stress disorder. Genome Medicine 2017, 9: 99. PMID: 29178946, PMCID: PMC5702961, DOI: 10.1186/s13073-017-0491-4.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesLarge genome-wide association studiesPutative causal relationshipAnthropometric traitsBody shapeEvolutionary mechanismsTop associationsAssociation studiesReproductive behaviorGenetic correlationsPleiotropic effectsGenetic overlapFemale body shapePolygenic score approachTraitsMendelian randomization analysisSummary statisticsRandomization analysisHuman sexual behaviorMechanismADH1B: From alcoholism, natural selection, and cancer to the human phenome
Polimanti R, Gelernter J. ADH1B: From alcoholism, natural selection, and cancer to the human phenome. American Journal Of Medical Genetics Part B Neuropsychiatric Genetics 2017, 177: 113-125. PMID: 28349588, PMCID: PMC5617762, DOI: 10.1002/ajmg.b.32523.Peer-Reviewed Original ResearchConceptsHuman phenomeMultiple human tissuesPhenome-wide association studyMolecular functionsGene regulationPhenotypic traitsBioinformatics analysisEvolutionary dataFunctional allelesAssociation studiesMetabolic traitsAlcohol metabolismMolecular pathwaysMultiple molecular pathwaysHuman evolutionPhenomeGenesADH1B geneTraitsComplex mechanismsHuman tissuesMetabolismAllelesADH1BADH1B locus
2016
Evidence of Polygenic Adaptation in the Systems Genetics of Anthropometric Traits
Polimanti R, Yang BZ, Zhao H, Gelernter J. Evidence of Polygenic Adaptation in the Systems Genetics of Anthropometric Traits. PLOS ONE 2016, 11: e0160654. PMID: 27537407, PMCID: PMC4990182, DOI: 10.1371/journal.pone.0160654.Peer-Reviewed Original ResearchConceptsPolygenic adaptationNatural selectionSystems geneticsProtein interaction networksWide association studyPolygenic mechanismsEuropean populationsPolygenic selectionAnthropometric traitsGene networksHuman genomeEpistatic interactionsInteraction networksEnrichment analysisGenetic signaturesSystems biologyAssociation studiesLipid transportMolecular processesAdaptation signalsLocomotory behaviorTraitsSelective mechanismGeneticsInfection resistance
2015
Dissecting ancestry genomic background in substance dependence genome-wide association studies
Polimanti R, Yang C, Zhao H, Gelernter J. Dissecting ancestry genomic background in substance dependence genome-wide association studies. Pharmacogenomics 2015, 16: 1487-1498. PMID: 26267224, PMCID: PMC4632979, DOI: 10.2217/pgs.15.91.Peer-Reviewed Original ResearchMeSH KeywordsAlcoholismAlgorithmsAllelesBlack or African AmericanGene FrequencyGene-Environment InteractionGenetic Predisposition to DiseaseGenetic VariationGenome-Wide Association StudyHaplotypesHumansMolecular Sequence AnnotationOpioid-Related DisordersSubstance-Related DisordersTobacco Use DisorderWhite PeopleConceptsGenome-wide association studiesGenomic backgroundFunctional allelesAssociation studiesCommon functional allelesWide association studyLocal haplotype structureGenetic lociSD traitHaplotype structureRelevant genesGenesLociInteractive partnersPopulation diversityHigh frequency differencesAllelesFrequency differenceGenomeTraitsDiversityRoleVariantsGenetic diversity of disease-associated loci in Turkish population
Karaca S, Cesuroglu T, Karaca M, Erge S, Polimanti R. Genetic diversity of disease-associated loci in Turkish population. Journal Of Human Genetics 2015, 60: 193-198. PMID: 25716910, DOI: 10.1038/jhg.2015.8.Peer-Reviewed Original ResearchConceptsHealth-related traitsGenetic diversityNon-European ancestryHuman genetic variationDisease-associated lociGenetic structureComplex traitsGenetic variationTraitsEuropean individualsGenesEast populationDiversityGenetic featuresAncestryPolygenic scoresMiddle East populationLociPopulationPeculiar genetic featuresGenetic predispositionHuman groupsLarge numberTurkish populationLast finding