2024
Effects of genetically predicted posttraumatic stress disorder on autoimmune phenotypes
Maihofer A, Ratanatharathorn A, Hemmings S, Costenbader K, Michopoulos V, Polimanti R, Rothbaum A, Seedat S, Mikita E, Smith A, Salem R, Shaffer R, Wu T, Sebat J, Ressler K, Stein M, Koenen K, Wolf E, Sumner J, Nievergelt C. Effects of genetically predicted posttraumatic stress disorder on autoimmune phenotypes. Translational Psychiatry 2024, 14: 172. PMID: 38561342, PMCID: PMC10984931, DOI: 10.1038/s41398-024-02869-0.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderMendelian randomizationTwo-sample Mendelian randomizationLinkage disequilibrium score regressionGenome-wide significant single nucleotide polymorphismsCorrelated horizontal pleiotropyGenetic architectures of phenotypesMultivariable MR analysisSignificant single nucleotide polymorphismsAssociation of posttraumatic stress disorderCausal effectsSingle nucleotide polymorphismsGenetic correlationsMR-PRESSOHorizontal pleiotropyStress disorderMR analysisScore regressionGenetic architectureC-reactive proteinInverse varianceMR estimatesNucleotide polymorphismsPathway variablesEpidemiological evidenceClinical spectrum of Transthyretin amyloidogenic mutations among diverse population origins
De Lillo A, Pathak G, Low A, De Angelis F, Abou Alaiwi S, Miller E, Fuciarelli M, Polimanti R. Clinical spectrum of Transthyretin amyloidogenic mutations among diverse population origins. Human Genomics 2024, 18: 31. PMID: 38523305, PMCID: PMC10962184, DOI: 10.1186/s40246-024-00596-7.Peer-Reviewed Original ResearchConceptsCardiac congenital anomaliesAmyloidogenic mutationsCross-ancestry meta-analysisCongenital anomaliesComplex genotype-phenotype correlationsVal122Ile mutationGenotype-phenotype correlationPeripheral nerve disordersHereditary form of amyloidosisAncestry-specificCross-ancestryEuropean-descent individualsEast AsiansTTR-related amyloidosisIndividuals of African descentPopulation originClinical presentationAtrioventricular blockClinical spectrumDelayed diagnosisTTR mutationsAfrican descentNerve disordersTransthyretin mutationMutations
2023
Characterizing the polygenic architecture of complex traits in populations of East Asian and European descent
De Lillo A, Wendt F, Pathak G, Polimanti R. Characterizing the polygenic architecture of complex traits in populations of East Asian and European descent. Human Genomics 2023, 17: 67. PMID: 37475089, PMCID: PMC10360343, DOI: 10.1186/s40246-023-00514-3.Peer-Reviewed Original Research
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 outcomeFAN1FNBP4RepeatsAn 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 studiesColitisAsthmaGenetically 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
Biobank Scale Pharmacogenomics Informs the Genetic Underpinnings of Simvastatin Use
Wendt FR, Koller D, Pathak GA, Jacoby D, Miller EJ, Polimanti R. Biobank Scale Pharmacogenomics Informs the Genetic Underpinnings of Simvastatin Use. Clinical Pharmacology & Therapeutics 2021, 110: 777-785. PMID: 33837531, PMCID: PMC8376807, DOI: 10.1002/cpt.2260.Peer-Reviewed Original ResearchConceptsLDL-C concentrationsSimvastatin useLow-density lipoprotein cholesterol concentrationsLipoprotein cholesterol concentrationsDrug-metabolizing enzymesElectronic medical recordsStatin therapyStatin treatmentActivity scoreMedical recordsPilot cohortCholesterol concentrationsEuropean ancestry participantsMetabolizer phenotypeClinical decisionNAT2 allelesPolygenic riskNAT2Good responseUK BiobankBiological mechanismsPharmacogenesAssociationPotential benefitsPhenotypeCross-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
Non-coding variants contribute to the clinical heterogeneity of TTR amyloidosis
Iorio A, De Lillo A, De Angelis F, Di Girolamo M, Luigetti M, Sabatelli M, Pradotto L, Mauro A, Mazzeo A, Stancanelli C, Perfetto F, Frusconi S, My F, Manfellotto D, Fuciarelli M, Polimanti R. Non-coding variants contribute to the clinical heterogeneity of TTR amyloidosis. European Journal Of Human Genetics 2017, 25: 1055-1060. PMID: 28635949, PMCID: PMC5558178, DOI: 10.1038/ejhg.2017.95.Peer-Reviewed Original ResearchADH1B: 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 locusPopulation diversity of the genetically determined TTR expression in human tissues and its implications in TTR amyloidosis
Iorio A, De Angelis F, Di Girolamo M, Luigetti M, Pradotto LG, Mazzeo A, Frusconi S, My F, Manfellotto D, Fuciarelli M, Polimanti R. Population diversity of the genetically determined TTR expression in human tissues and its implications in TTR amyloidosis. BMC Genomics 2017, 18: 254. PMID: 28335735, PMCID: PMC5364715, DOI: 10.1186/s12864-017-3646-1.Peer-Reviewed Original ResearchConceptsGenotype-phenotype correlationHuman populationComplex genotype-phenotype correlationsFamilial amyloidotic cardiomyopathyTTR expressionTTR amyloidosisGTEx projectGenome ProjectSkeletal muscle tissueAncestral groupsAncestry diversityRelevant tissuesScandinavian populationsAmyloidotic cardiomyopathyPopulation diversityAncestry groupsExpressionHuman tissuesDiversityMuscle tissueHereditary diseasePolygenic scoresTissueClinical variabilityLesser extent
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