2024
Gene discovery and biological insights into anxiety disorders from a large-scale multi-ancestry genome-wide association study
Friligkou E, Løkhammer S, Cabrera-Mendoza B, Shen J, He J, Deiana G, Zanoaga M, Asgel Z, Pilcher A, Di Lascio L, Makharashvili A, Koller D, Tylee D, Pathak G, Polimanti R. Gene discovery and biological insights into anxiety disorders from a large-scale multi-ancestry genome-wide association study. Nature Genetics 2024, 56: 2036-2045. PMID: 39294497, DOI: 10.1038/s41588-024-01908-2.Peer-Reviewed Original ResearchGenome-wide association studiesAnxiety disordersAssociation studiesMulti-ancestry genome-wide association studyPathogenesis of anxiety disordersHeritability of anxietyLocal genetic correlationProteome-wide analysisIndividuals of European descentAssociated with anxietyMulti-omics informationWidespread pleiotropyTranscriptome-widePolygenic risk scoresBipolar disorderAncestry-specificGene discoveryContinental groupsLimbic systemEast Asian groupsBiological insightsAnxietyEntorhinal cortexPhysical health domainBrain-specificDistinguishing vulnerability and resilience to posttraumatic stress disorder evaluating traumatic experiences, genetic risk and electronic health records
Løkhammer S, Koller D, Wendt F, Choi K, He J, Friligkou E, Overstreet C, Gelernter J, Hellard S, Polimanti R. Distinguishing vulnerability and resilience to posttraumatic stress disorder evaluating traumatic experiences, genetic risk and electronic health records. Psychiatry Research 2024, 337: 115950. PMID: 38744179, PMCID: PMC11156529, DOI: 10.1016/j.psychres.2024.115950.Peer-Reviewed Original ResearchElectronic health recordsPosttraumatic stress disorderHealth recordsPTSD vulnerabilityUK Biobank (UKBPhenome-wide association studyRisk scorePhenotype risk scoreUs Research ProgramPolygenic risk scoresStress disorderAoU participantsUKB participantsPresence of posttraumatic stress disorderTrauma burdenGenetic riskPosttraumatic stress disorder symptomsAssociation studiesPheWASClinical comorbiditiesComorbid associationsEye conditionsAOUInverse relationshipMultiple phenotypesSex differences in the pleiotropy of hearing difficulty with imaging-derived phenotypes: a brain-wide investigation
He J, Cabrera-Mendoza B, De Angelis F, Pathak G, Koller D, Curhan S, Curhan G, Mecca A, van Dyck C, Polimanti R. Sex differences in the pleiotropy of hearing difficulty with imaging-derived phenotypes: a brain-wide investigation. Brain 2024, 147: 3395-3408. PMID: 38454550, PMCID: PMC11449129, DOI: 10.1093/brain/awae077.Peer-Reviewed Original ResearchImaging-derived phenotypesHearing difficultiesBrain imaging-derived phenotypesSex-combined analysisLatent causal variable analysesMendelian randomization approachGeneralized linear regression analysisLocal genetic correlation analysisMultivariate generalized linear regression analysisGenome-wide association studiesLatent causal variableGenetic correlation analysisGenetic correlationsLocal genetic correlationMendelian randomizationPeripheral auditory systemOlder adultsGWAS dataLinear regression analysisHealth burdenGenomic regionsAssociation studiesPleiotropic regionsSex differencesTranscriptome regulation
2022
Phenome-wide association study of loci harboring de novo tandem repeat mutations in UK Biobank exomes
Wendt F, Pathak G, Polimanti R. Phenome-wide association study of loci harboring de novo tandem repeat mutations in UK Biobank exomes. Nature Communications 2022, 13: 7682. PMID: 36509785, PMCID: PMC9744822, DOI: 10.1038/s41467-022-35423-x.Peer-Reviewed Original ResearchConceptsProtein structureTandem repeatsTandem repeat mutationsPhenome-wide association studyAlters protein structureGenetic variationAssociation studiesEuropean ancestry participantsUK BiobankCarotid intima-media thicknessTR mutationsIntima-media thicknessMicroRNA-184Repeat mutationsFamily-based designsTestable hypothesesLociPopulation levelRespiratory outcomesMutationsDisease outcomeFAN1FNBP4RepeatsDenisovan and Neanderthal archaic introgression differentially impacted the genetics of complex traits in modern populations
Koller D, Wendt F, Pathak G, De Lillo A, De Angelis F, Cabrera-Mendoza B, Tucci S, Polimanti R. Denisovan and Neanderthal archaic introgression differentially impacted the genetics of complex traits in modern populations. BMC Biology 2022, 20: 249. PMID: 36344982, PMCID: PMC9641937, DOI: 10.1186/s12915-022-01449-2.Peer-Reviewed Original ResearchConceptsArchaic introgressionComplex traitsDenisovan introgressionNeanderthal allelesNeanderthal introgressionSignatures of admixtureAncestry groupsModern populationsPhenome-wide association studyModern human populationsMajor histocompatibility complex regionIntrogressionEvolutionary pressureGenetic poolDisease heritabilityGenomic signaturesEAS populationsExtinct NeanderthalsAssociation studiesMetabolic traitsDenisovansUK BiobankRed hair colorEuropean descentHuman traitsAn 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 ResearchConceptsRisk 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 studiesColitisAsthmaUsing 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 descent
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 variance
2019
Phenome-wide association study of TTR and RBP4 genes in 361,194 individuals reveals novel insights in the genetics of hereditary and wildtype transthyretin amyloidoses
De Lillo A, De Angelis F, Di Girolamo M, Luigetti M, Frusconi S, Manfellotto D, Fuciarelli M, Polimanti R. Phenome-wide association study of TTR and RBP4 genes in 361,194 individuals reveals novel insights in the genetics of hereditary and wildtype transthyretin amyloidoses. Human Genetics 2019, 138: 1331-1340. PMID: 31659433, DOI: 10.1007/s00439-019-02078-6.Peer-Reviewed Original ResearchConceptsNon-coding variantsPhenome-wide association studyAssociation studiesNovel insightsPhenotypic traitsMolecular basisPossible modifier genesRBP4 geneModifier genesRelevant phenotypesTTR locusGenesTTR functionTransthyretin amyloidosesMultiple testing correctionGene variationRBP4 variantsGeneticsPhenotypeTransthyretin geneTTR geneConvergent associationsHereditary formsClinical phenotypeVariants
2017
A 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 locusSchizophrenia 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
Phenome-Wide Association Study for Alcohol and Nicotine Risk Alleles in 26394 Women
Polimanti R, Kranzler HR, Gelernter J. Phenome-Wide Association Study for Alcohol and Nicotine Risk Alleles in 26394 Women. Neuropsychopharmacology 2016, 41: 2688-2696. PMID: 27187070, PMCID: PMC5026736, DOI: 10.1038/npp.2016.72.Peer-Reviewed Original ResearchConceptsHealth initiativesRisk allelesSocioeconomic statusPhenome-wide association studyWomen's Health InitiativeMetabolism-related mechanismsMedication useLung cancerTobacco useDietary habitsSmoking behaviorNicotine useReproductive historyReproductive healthSuggestive findingsAlcohol useAnthropometric characteristicsMental healthHealth conditionsMetabolic conditionsCausative relationshipAssociation studiesDrinking behaviorADH1BAssociation