2022
APOL1 Risk Variants, Acute Kidney Injury, and Death in Participants With African Ancestry Hospitalized With COVID-19 From the Million Veteran Program
Hung AM, Shah SC, Bick AG, Yu Z, Chen HC, Hunt CM, Wendt F, Wilson O, Greevy RA, Chung CP, Suzuki A, Ho YL, Akwo E, Polimanti R, Zhou J, Reaven P, Tsao PS, Gaziano JM, Huffman JE, Joseph J, Luoh SW, Iyengar S, Chang KM, Casas JP, Matheny ME, O’Donnell C, Cho K, Tao R, Susztak K, Robinson-Cohen C, Tuteja S, Siew ED, Hung A, Wallbom A, Palacio A, Robey B, Jhala D, Fujii D, Cohen D, Boyko E, Jacono F, Villareal G, Garcon H, Gaziano J, Lichy J, Norton J, Beckham J, Whittle J, Huffman J, Moser J, Greco J, Walsh J, Harley J, Wells J, Klein J, Moorman J, Constans J, Fayad J, Casas J, Xu J, Liao K, Alexander K, Cho K, Hammer K, Oursler K, Mattocks K, Chang K, Dellitalia L, Hamner M, Whooley M, Murdoch M, Gaddy M, Godschalk M, Rauchman M, Huq M, Tandon N, Kosik N, Ratcliffe N, Okusaga O, Roussos P, Strollo P, Meyer P, Sriram P, Wilson P, Liang P, Tsao P, Balasubramanian P, Ramoni R, McArdle R, Hauger R, Servatius R, Smith R, Striker R, Mathew R, Gappy S, Pyarajan S, Gutierrez S, Gupta S, Aguayo S, Sharma S, Damrauer S, Kinlay S, Yeh S, Luoh S, Tuteja S, Mastorides S, Iyengar S, Bhushan S, Muralidhar S, Ahuja S, Liangpunsakul S, Assimes T, Morgan T, Stapley T, Sun Y, Ballas Z. APOL1 Risk Variants, Acute Kidney Injury, and Death in Participants With African Ancestry Hospitalized With COVID-19 From the Million Veteran Program. JAMA Internal Medicine 2022, 182: 386-395. PMID: 35089317, PMCID: PMC8980930, DOI: 10.1001/jamainternmed.2021.8538.Peer-Reviewed Original ResearchConceptsAcute kidney injuryNormal kidney functionHigh-risk groupAPOL1 risk variantsKidney functionAKI severityKidney injuryCohort studyMillion Veteran ProgramHigher oddsCOVID-19-associated acute kidney injuryRisk variantsMultivariable logistic regression analysisCOVID-19AKI risk factorsAKI severity stageRetrospective cohort studyAfrican ancestryApolipoprotein L1COVID-19 infectionCoronavirus disease 2019Logistic regression analysisHigh mortality rateVeteran ProgramAPOL1 kidney risk variants
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 benefitsPhenotype
2020
Epigenetic profiling of Italian patients identified methylation sites associated with hereditary transthyretin amyloidosis
De Lillo A, Pathak GA, De Angelis F, Di Girolamo M, Luigetti M, Sabatelli M, Perfetto F, Frusconi S, Manfellotto D, Fuciarelli M, Polimanti R. Epigenetic profiling of Italian patients identified methylation sites associated with hereditary transthyretin amyloidosis. Clinical Epigenetics 2020, 12: 176. PMID: 33203445, PMCID: PMC7672937, DOI: 10.1186/s13148-020-00967-6.Peer-Reviewed Original ResearchConceptsEpigenome-wide association studiesMethylation sitesEpigenetic differencesSignificant epigenetic differencesProtein interaction networksSignificant methylation changesAmyloidogenic mutationsDisease-causing mutationsProtein interactorsEpigenetic regulationHigh phenotypic variabilityEpigenetic profilingMethylation changesInteraction networksGene regionBiological processesMolecular mechanismsAssociation studiesMolecular pathwaysCoding mutationsPhenotypic variabilityNovel insightsGenesFiber formationMutationsGenetically-regulated transcriptomics & copy number variation of proctitis points to altered mitochondrial and DNA repair mechanisms in individuals of European ancestry
Pathak GA, Polimanti R, Silzer TK, Wendt FR, Chakraborty R, Phillips NR. Genetically-regulated transcriptomics & copy number variation of proctitis points to altered mitochondrial and DNA repair mechanisms in individuals of European ancestry. BMC Cancer 2020, 20: 954. PMID: 33008348, PMCID: PMC7530964, DOI: 10.1186/s12885-020-07457-1.Peer-Reviewed Original ResearchConceptsWhole blood tissuesCopy number variationsNumber variationsGene expressionGenome-Wide Human SNP Array 6.0Mitochondrial apoptosis regulationRNA-seq informationGenetic variantsDNA repair mechanismsGene expression changesDNA repair processesGene expression associationsGene expression profilesGene network informationDNA repair genesCopy number dataCopy number analysisGene OntologyApoptosis regulationDNA repairEnriched pathwaysEnriched processesOrganismal injuryTranscriptomic profilesExpression changesAssociation of OPRM1 Functional Coding Variant With Opioid Use Disorder
Zhou H, Rentsch CT, Cheng Z, Kember RL, Nunez YZ, Sherva RM, Tate JP, Dao C, Xu K, Polimanti R, Farrer LA, Justice AC, Kranzler HR, Gelernter J. Association of OPRM1 Functional Coding Variant With Opioid Use Disorder. JAMA Psychiatry 2020, 77: 1072-1080. PMID: 32492095, PMCID: PMC7270886, DOI: 10.1001/jamapsychiatry.2020.1206.Peer-Reviewed Original ResearchConceptsOpioid use disorderUse disordersMendelian randomization analysisAfrican American individualsMAIN OUTCOMEFunctional coding variantSignificant associationCausal associationRandomization analysisElectronic health record dataCurrent opioid crisisAmerican individualsHealth record dataCognitive performanceInternational Statistical ClassificationRelated Health ProblemsPotential causal associationAmerican controlsEuropean American controlsAfrican-American controlsCoding variantBuprenorphine treatmentOUD diagnosisTobacco smokingNinth RevisionReproducible 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 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 17Genome-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 samplesEvidence of causal effect of major depression on alcohol dependence: findings from the psychiatric genomics consortium
Polimanti R, Peterson RE, Ong JS, MacGregor S, Edwards AC, Clarke TK, Frank J, Gerring Z, Gillespie NA, Lind PA, Maes HH, Martin NG, Mbarek H, Medland SE, Streit F, Agrawal A, Edenberg H, Kendler K, Lewis C, Sullivan P, Wray N, Gelernter J, Derks E. Evidence of causal effect of major depression on alcohol dependence: findings from the psychiatric genomics consortium. Psychological Medicine 2019, 49: 1218-1226. PMID: 30929657, PMCID: PMC6565601, DOI: 10.1017/s0033291719000667.Peer-Reviewed Original ResearchConceptsMajor depressionAlcohol dependenceAlcohol consumptionPsychiatric Genomics ConsortiumImportant public health concernMendelian randomizationPublic health concernUK BiobankClinical associationsHealth concernMR analysisReverse causationCausal roleNon-significant resultsCausal relationshipGenetic liabilityGenomics ConsortiumLinkage disequilibrium score regressionIntervention efforts
2018
Effect of the GSTM1 gene deletion on glycemic variability, sympatho-vagal balance and arterial stiffness in patients with metabolic syndrome, but without diabetes
Iorio A, Ylli D, Polimanti R, Picconi F, Maggio P, Francomano D, Aversa A, Manfellotto D, Fuciarelli M, Frontoni S. Effect of the GSTM1 gene deletion on glycemic variability, sympatho-vagal balance and arterial stiffness in patients with metabolic syndrome, but without diabetes. Diabetes Research And Clinical Practice 2018, 138: 158-168. PMID: 29452132, DOI: 10.1016/j.diabres.2018.02.006.Peer-Reviewed Original ResearchConceptsProtein kinase regulationGlutathione S-transferase geneCellular detoxification processesKinase regulationInvolvement of GSTRisk lociFunctional variantsGene deletionPutative roleDetoxification processDeletionGenesPolymorphism analysisOxidative stressCrucial roleGene polymorphism analysisGST gene polymorphismsNovel findingsGSTM1 gene deletionLociGSTM1 deletionRoleGSTRegulationPathway
2015
International warfarin genotype-guided dosing algorithms in the Turkish population and their preventive effects on major and life-threatening hemorrhagic events
Karaca S, Bozkurt NC, Cesuroglu T, Karaca M, Bozkurt M, Eskioglu E, Polimanti R. International warfarin genotype-guided dosing algorithms in the Turkish population and their preventive effects on major and life-threatening hemorrhagic events. Pharmacogenomics 2015, 16: 1109-1118. PMID: 26216670, DOI: 10.2217/pgs.15.58.Peer-Reviewed Original ResearchConceptsLife-threatening hemorrhagic eventsHemorrhagic eventsPharmacogenetic algorithmWarfarin doseTurkish patientsTherapeutic warfarin doseHistory of bleedingLarge multiethnic cohortTherapeutic warfarin dosesWarfarin pharmacogenetic algorithmsThromboembolic eventsWarfarin dosesPreventive effectTherapeutic doseMultiethnic cohortPatientsTurkish populationAbstractTextDoseWarfarinCohortBleedingHemorrhagicDoses
2013
Intronic rs2147363 Variant in ATP7B Transcription Factor-Binding Site Associated with Alzheimer's Disease
Bucossi S, Polimanti R, Ventriglia M, Mariani S, Siotto M, Ursini F, Trotta L, Scrascia F, Callea A, Vernieri F, Squitti R. Intronic rs2147363 Variant in ATP7B Transcription Factor-Binding Site Associated with Alzheimer's Disease. Journal Of Alzheimer's Disease 2013, 37: 453-459. PMID: 23948886, DOI: 10.3233/jad-130431.Peer-Reviewed Original ResearchConceptsLinkage disequilibriumDisease-causing variantsCis-regulatory elementsNon-coding regionsObserved genetic associationIntronic single nucleotide polymorphismSingle nucleotide polymorphismsTranscription factorsGenetic variationATP7B variantsSilico analysisRegulatory functionsLD analysisNucleotide polymorphismsGenetic associationSites AssociatedAlzheimer's diseaseAD riskKey roleVariantsATP7B geneATP7B Variants as Modulators of Copper Dyshomeostasis in Alzheimer’s Disease
Squitti R, Polimanti R, Siotto M, Bucossi S, Ventriglia M, Mariani S, Vernieri F, Scrascia F, Trotta L, Rossini PM. ATP7B Variants as Modulators of Copper Dyshomeostasis in Alzheimer’s Disease. NeuroMolecular Medicine 2013, 15: 515-522. PMID: 23760784, DOI: 10.1007/s12017-013-8237-y.Peer-Reviewed Original ResearchAntioxidant Status and APOE Genotype As Susceptibility Factors for Neurodegeneration in Alzheimer's Disease and Vascular Dementia
Zito G, Polimanti R, Panetta V, Ventriglia M, Salustri C, Siotto MC, Moffa F, Altamura C, Vernieri F, Lupoi D, Cassetta E, Rossini PM, Squitti R. Antioxidant Status and APOE Genotype As Susceptibility Factors for Neurodegeneration in Alzheimer's Disease and Vascular Dementia. Rejuvenation Research 2013, 16: 51-56. PMID: 23216585, PMCID: PMC3582293, DOI: 10.1089/rej.2012.1383.Peer-Reviewed Original ResearchConceptsAntioxidant statusΕ4 alleleVascular dementiaHealthy controlsSerum total antioxidant statusOxidative stressHigher WMH scoresTotal antioxidant statusWhite matter hyperintensitiesAPOE ε4 alleleElderly healthy controlsWMH scoresVaD patientsAtrophy assessmentLipid dyshomeostasisNeurodegenerative processesMatter hyperintensitiesPathogenetic pathwaysApolipoprotein EAlzheimer typeSystem homeostasisAlzheimer's diseaseTAS concentrationDisease riskLipid metabolismMetal-score as a potential non-invasive diagnostic test for Alzheimer's disease.
Squitti R, Pasqualetti P, Polimanti R, Salustri C, Moffa F, Cassetta E, Lupoi D, Ventriglia M, Cortesi M, Siotto M, Vernieri F, Rossini PM. Metal-score as a potential non-invasive diagnostic test for Alzheimer's disease. Current Alzheimer Research 2013, 10: 191-8. PMID: 23036026, DOI: 10.2174/1567205011310020009.Peer-Reviewed Original Research
2012
Association of K832R and R952K SNPs of Wilson's Disease Gene with Alzheimer's Disease
Bucossi S, Polimanti R, Mariani S, Ventriglia M, Bonvicini C, Migliore S, Manfellotto D, Salustri C, Vernieri F, Rossini PM, Squitti R. Association of K832R and R952K SNPs of Wilson's Disease Gene with Alzheimer's Disease. Journal Of Alzheimer's Disease 2012, 29: 913-919. PMID: 22356903, DOI: 10.3233/jad-2012-111997.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphatasesAgedAged, 80 and overAlzheimer DiseaseArginineCation Transport ProteinsCopper-transporting ATPasesFemaleGenetic Association StudiesGenetic Predisposition to DiseaseGenotypeHumansLinkage DisequilibriumLogistic ModelsLysineMaleMiddle AgedPolymorphism, Single NucleotideConceptsDisease patientsAD patientsApolipoprotein E ε4 allele frequencyAPOE ε4 variantΕ4 allele frequencyAlzheimer's disease patientsATP7B geneLocus of susceptibilityΕ4 variantHealthy controlsNeurodegenerative processesAlzheimer's diseasePatientsRisk allelesDiseaseCopper dysfunctionR alleleATP7B allelesWilson disease geneK alleleDisease genesGSTM1 null genotype as risk factor for late-onset Alzheimer's disease in Italian patients
Piacentini S, Polimanti R, Squitti R, Ventriglia M, Cassetta E, Vernieri F, Rossini PM, Manfellotto D, Fuciarelli M. GSTM1 null genotype as risk factor for late-onset Alzheimer's disease in Italian patients. Journal Of The Neurological Sciences 2012, 317: 137-140. PMID: 22381228, DOI: 10.1016/j.jns.2012.01.026.Peer-Reviewed Original ResearchConceptsGSTM1 null genotypeAlzheimer's diseaseNull genotypeRisk factorsItalian patientsCause of ADLate-onset Alzheimer's diseaseLogistic regression analysisGlutathione S-transferaseCase-control populationAD patientsAD riskGSTM1 geneGSTT1 genesGenotype distributionDisease riskNeurodegenerative disordersDiseasePatientsOxidative stressEndogenous metabolitesCommon formRegression analysisPositive associationGSTM1
2011
GSTO1*E155del polymorphism associated with increased risk for late-onset Alzheimer's disease: Association hypothesis for an uncommon genetic variant
Piacentini S, Polimanti R, Squitti R, Mariani S, Migliore S, Vernieri F, Rossini PM, Manfellotto D, Fuciarelli M. GSTO1*E155del polymorphism associated with increased risk for late-onset Alzheimer's disease: Association hypothesis for an uncommon genetic variant. Neuroscience Letters 2011, 506: 203-207. PMID: 22100662, DOI: 10.1016/j.neulet.2011.11.005.Peer-Reviewed Original ResearchConceptsUncommon genetic variantsGSTO1-1Genetic variantsClass genesGlutathione S-transferaseGenetic variationMultifunctional enzymeCellular detoxificationAlzheimer's diseaseGSTO2 genesGenetic linkageAllele-specific PCRS-transferaseChromosome 10qAD riskGene polymorphismsInterleukin-1β activationSpecific PCRPathophysiology of ADGenesLate-onset Alzheimer's diseasePolymorphismAD risk factorsOxidative stressPCR-RFLP