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 smokingGenome-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
2020
Reproducible 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 ResearchConceptsNovel 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 GWASs
2019
Genome-wide association study of post-traumatic stress disorder reexperiencing symptoms in >165,000 US veterans
Gelernter J, Sun N, Polimanti R, Pietrzak R, Levey DF, Bryois J, Lu Q, Hu Y, Li B, Radhakrishnan K, Aslan M, Cheung KH, Li Y, Rajeevan N, Sayward F, Harrington K, Chen Q, Cho K, Pyarajan S, Sullivan PF, Quaden R, Shi Y, Hunter-Zinck H, Gaziano JM, Concato J, Zhao H, Stein MB. Genome-wide association study of post-traumatic stress disorder reexperiencing symptoms in >165,000 US veterans. Nature Neuroscience 2019, 22: 1394-1401. PMID: 31358989, PMCID: PMC6953633, DOI: 10.1038/s41593-019-0447-7.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesAssociation studiesHigh linkage disequilibrium regionLinkage disequilibrium regionWide association studyDisequilibrium regionBioinformatics analysisTranscriptomic profilesMillion Veteran ProgramChromosome 17Genetic risk factorsNew insightsUK Biobank dataReexperiencing of traumaStriatal medium spiny neuronsVeteran ProgramSignificant regionsCAMKVEuropean AmericansBiobank dataMedium spiny neuronsTCF4BiologyKANSL1African American cohortGenome-wide Association Study of Maximum Habitual Alcohol Intake in >140,000 U.S. European and African American Veterans Yields Novel Risk Loci
Gelernter J, Sun N, Polimanti R, Pietrzak RH, Levey DF, Lu Q, Hu Y, Li B, Radhakrishnan K, Aslan M, Cheung KH, Li Y, Rajeevan N, Sayward F, Harrington K, Chen Q, Cho K, Honerlaw J, Pyarajan S, Lencz T, Quaden R, Shi Y, Hunter-Zinck H, Gaziano JM, Kranzler HR, Concato J, Zhao H, Stein MB, Program D, Program M. Genome-wide Association Study of Maximum Habitual Alcohol Intake in >140,000 U.S. European and African American Veterans Yields Novel Risk Loci. Biological Psychiatry 2019, 86: 365-376. PMID: 31151762, PMCID: PMC6919570, DOI: 10.1016/j.biopsych.2019.03.984.Peer-Reviewed Original ResearchConceptsAdditional genome-wide significant lociRisk lociWide association study (GWAS) analysisAssociation studiesGenome-wide significant lociGenome-wide association studiesGenetic correlationsWide association studyNovel risk lociAlcohol-related traitsStrong statistical supportSmoking-related traitsAdditional genomesSignificant lociPancreatic delta cellsChromosome 4Chromosome 11Protein productsChromosome 8Quantitative phenotypesMillion Veteran ProgramVeterans Affairs Million Veteran ProgramLociCell typesChromosome 17
2017
Schizophrenia and substance use comorbidity: a genome-wide perspective
Polimanti R, Agrawal A, Gelernter J. Schizophrenia and substance use comorbidity: a genome-wide perspective. Genome Medicine 2017, 9: 25. PMID: 28327175, PMCID: PMC5359801, DOI: 10.1186/s13073-017-0423-3.Peer-Reviewed Original ResearchConceptsSubstance use disordersPublic health messagesPremature mortalityPsychiatric disordersUse disordersDual diagnosisHealth messagesRecent genetic investigationsDiagnosisSchizophreniaDisordersGenetic investigationsWide association studyAssociation studiesComorbiditiesMortalityGenome-wide perspective
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 differenceGenomeTraitsDiversityRoleVariants
2013
Linkage Disequilibrium and Haplotype Analysis of the ATP7B Gene in Alzheimer's Disease
Squitti R, Polimanti R, Bucossi S, Ventriglia M, Mariani S, Manfellotto D, Vernieri F, Cassetta E, Ursini F, Rossini PM. Linkage Disequilibrium and Haplotype Analysis of the ATP7B Gene in Alzheimer's Disease. Rejuvenation Research 2013, 16: 3-10. PMID: 22950421, PMCID: PMC3582274, DOI: 10.1089/rej.2012.1357.Peer-Reviewed Original ResearchConceptsCopper-binding domainSingle nucleotide polymorphismsInformative single nucleotide polymorphismsAssociation studiesLD blocksRole of ATP7BWide association studyLinkage disequilibrium analysisGenetic structureVariants/haplotypesGenetic association analysisTransmembrane domainSignificant lociGene sequencesGenetic association studiesATP7B geneGene regionAssociation analysisGenesDisequilibrium analysisLinkage disequilibriumNovel insightsCopper dyshomeostasisStrong LDMultiple testing correction