Featured Publications
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
2022
A MUC5B Gene Polymorphism, rs35705950-T, Confers Protective Effects Against COVID-19 Hospitalization but Not Severe Disease or Mortality
Verma A, Minnier J, Wan ES, Huffman JE, Gao L, Joseph J, Ho YL, Wu WC, Cho K, Gorman BR, Rajeevan N, Pyarajan S, Garcon H, Meigs JB, Sun YV, Reaven PD, McGeary JE, Suzuki A, Gelernter J, Lynch JA, Petersen JM, Zekavat SM, Natarajan P, Dalal S, Jhala DN, Arjomandi M, Gatsby E, Lynch KE, Bonomo RA, Freiberg M, Pathak GA, Zhou JJ, Donskey CJ, Madduri RK, Wells QS, Huang R, Polimanti R, Chang KM, Liao KP, Tsao PS, Wilson PWF, Hung A, O’Donnell C, Gaziano JM, Hauger RL, Iyengar S, Luoh SW, Initiative T. A MUC5B Gene Polymorphism, rs35705950-T, Confers Protective Effects Against COVID-19 Hospitalization but Not Severe Disease or Mortality. American Journal Of Respiratory And Critical Care Medicine 2022, 206: 1220-1229. PMID: 35771531, PMCID: PMC9746845, DOI: 10.1164/rccm.202109-2166oc.Peer-Reviewed Original ResearchConceptsCOVID-19 hospitalizationIdiopathic pulmonary fibrosisMillion Veteran ProgramHost Genetics InitiativeAcute respiratory syndrome coronavirus 2 infectionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectionGene polymorphismsSyndrome coronavirus 2 infectionCoronavirus 2 infectionConfer protective effectsCOVID-19 positivityCoronavirus disease (COVID-19) infectionElectronic health recordsMVP subjectsPneumonia eventsClinical outcomesPulmonary fibrosisCOVID-19 Host Genetics InitiativeClinical eventsSevere outcomesProtective effectSevere diseaseRs35705950Disease severityMVP participants
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
2018
Transancestral GWAS of alcohol dependence reveals common genetic underpinnings with psychiatric disorders
Walters RK, Polimanti R, Johnson EC, McClintick JN, Adams MJ, Adkins AE, Aliev F, Bacanu SA, Batzler A, Bertelsen S, Biernacka JM, Bigdeli TB, Chen LS, Clarke TK, Chou YL, Degenhardt F, Docherty AR, Edwards AC, Fontanillas P, Foo JC, Fox L, Frank J, Giegling I, Gordon S, Hack LM, Hartmann AM, Hartz SM, Heilmann-Heimbach S, Herms S, Hodgkinson C, Hoffmann P, Jan Hottenga J, Kennedy MA, Alanne-Kinnunen M, Konte B, Lahti J, Lahti-Pulkkinen M, Lai D, Ligthart L, Loukola A, Maher BS, Mbarek H, McIntosh AM, McQueen MB, Meyers JL, Milaneschi Y, Palviainen T, Pearson JF, Peterson RE, Ripatti S, Ryu E, Saccone NL, Salvatore JE, Sanchez-Roige S, Schwandt M, Sherva R, Streit F, Strohmaier J, Thomas N, Wang JC, Webb BT, Wedow R, Wetherill L, Wills AG, Boardman J, Chen D, Choi D, Copeland W, Culverhouse R, Dahmen N, Degenhardt L, Domingue B, Elson S, Frye M, Gäbel W, Hayward C, Ising M, Keyes M, Kiefer F, Kramer J, Kuperman S, Lucae S, Lynskey M, Maier W, Mann K, Männistö S, Müller-Myhsok B, Murray A, Nurnberger J, Palotie A, Preuss U, Räikkönen K, Reynolds M, Ridinger M, Scherbaum N, Schuckit M, Soyka M, Treutlein J, Witt S, Wodarz N, Zill P, Adkins D, Boden J, Boomsma D, Bierut L, Brown S, Bucholz K, Cichon S, Costello E, de Wit H, Diazgranados N, Dick D, Eriksson J, Farrer L, Foroud T, Gillespie N, Goate A, Goldman D, Grucza R, Hancock D, Harris K, Heath A, Hesselbrock V, Hewitt J, Hopfer C, Horwood J, Iacono W, Johnson E, Kaprio J, Karpyak V, Kendler K, Kranzler H, Krauter K, Lichtenstein P, Lind P, McGue M, MacKillop J, Madden P, Maes H, Magnusson P, Martin N, Medland S, Montgomery G, Nelson E, Nöthen M, Palmer A, Pedersen N, Penninx B, Porjesz B, Rice J, Rietschel M, Riley B, Rose R, Rujescu D, Shen P, Silberg J, Stallings M, Tarter R, Vanyukov M, Vrieze S, Wall T, Whitfield J, Zhao H, Neale B, Gelernter J, Edenberg H, Agrawal A. Transancestral GWAS of alcohol dependence reveals common genetic underpinnings with psychiatric disorders. Nature Neuroscience 2018, 21: 1656-1669. PMID: 30482948, PMCID: PMC6430207, DOI: 10.1038/s41593-018-0275-1.Peer-Reviewed Original ResearchConceptsGenetic underpinningsGenome-wide association studiesGenome-wide dataLarge genome-wide association studiesGenome-wide significant effectComplex polygenic architectureSignificant genetic correlationsPolygenic architectureGenetic distinctionCommon genetic underpinningsAssociation studiesGenetic relationshipsGenetic correlationsGenetic ancestryFamily-based studyUse of cigarettesAttention deficit hyperactivity disorderMultivariate Pattern Analysis of Genotype–Phenotype Relationships in Schizophrenia
Zheutlin AB, Chekroud AM, Polimanti R, Gelernter J, Sabb FW, Bilder RM, Freimer N, London ED, Hultman CM, Cannon TD. Multivariate Pattern Analysis of Genotype–Phenotype Relationships in Schizophrenia. Schizophrenia Bulletin 2018, 44: 1045-1052. PMID: 29534239, PMCID: PMC6101611, DOI: 10.1093/schbul/sby005.Peer-Reviewed Original ResearchConceptsMultivariate pattern analysisIndependent samplesVisual memoryCognitive endophenotypesPredictive strengthSchizophreniaMemoryIndividual variationPattern analysisSingle predictorCertain domainsDiscovery samplePsychiatric patientsPolygenic risk scoresPredictive powerScoresEndophenotypesPotential relationshipRelationshipRandom forestGenetic risk variantsLimited setPredictorsComprehensive setSamples
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 extentA genome-wide gene-by-trauma interaction study of alcohol misuse in two independent cohorts identifies PRKG1 as a risk locus
Polimanti R, Kaufman J, Zhao H, Kranzler HR, Ursano RJ, Kessler RC, Gelernter J, Stein MB. A genome-wide gene-by-trauma interaction study of alcohol misuse in two independent cohorts identifies PRKG1 as a risk locus. Molecular Psychiatry 2017, 23: 154-160. PMID: 28265120, PMCID: PMC5589475, DOI: 10.1038/mp.2017.24.Peer-Reviewed Original ResearchConceptsGenome-wide interaction studyGene Ontology (GO) enrichment analysisOntology enrichment analysisProtein kinase 1Protein regulationSame effect directionCyclic GMP-dependent protein kinase 1Circadian rhythm regulationRisk lociWide geneEnrichment analysisInteraction studiesKinase 1Individual genetic riskPsychiatric geneticsCalcium-activated potassium channelsGenesLociPRKG1Potassium channelsEffect directionRhythm regulationAlcohol use problemsRegulationAlcohol misuse
2016
Genetic factor common to schizophrenia and HIV infection is associated with risky sexual behavior: antagonistic vs. synergistic pleiotropic SNPs enriched for distinctly different biological functions
Wang Q, Polimanti R, Kranzler HR, Farrer LA, Zhao H, Gelernter J. Genetic factor common to schizophrenia and HIV infection is associated with risky sexual behavior: antagonistic vs. synergistic pleiotropic SNPs enriched for distinctly different biological functions. Human Genetics 2016, 136: 75-83. PMID: 27752767, PMCID: PMC5215962, DOI: 10.1007/s00439-016-1737-8.Peer-Reviewed Original Research
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
2014
GSTM1, GSTP1, and GSTT1 genetic variability in Turkish and worldwide populations
Karaca S, Karaca M, Cesuroglu T, Erge S, Polimanti R. GSTM1, GSTP1, and GSTT1 genetic variability in Turkish and worldwide populations. American Journal Of Human Biology 2014, 27: 310-316. PMID: 25515186, DOI: 10.1002/ajhb.22671.Peer-Reviewed Original ResearchConceptsHuman Genome Diversity ProjectGenetic association studiesSequence variationAssociation studiesFunctional variantsHigh linkage disequilibriumFuture genetic association studiesWorldwide populationCommon functional variantsGenetic diversityGenetic variabilityGenome ProjectOxidative stress-related diseasesGST genesLinkage disequilibriumEastern populationsDiversity ProjectGSTP1 functionStress-related diseasesStudy of diseasesGenetic polymorphismsSequenom MassARRAY platformPolymorphismVariantsGlutathione S-transferase variantsHaplotype differences for copy number variants in the 22q11.23 region among human populations: a pigmentation-based model for selective pressure
Polimanti R, Piacentini S, Iorio A, De Angelis F, Kozlov A, Novelletto A, Fuciarelli M. Haplotype differences for copy number variants in the 22q11.23 region among human populations: a pigmentation-based model for selective pressure. European Journal Of Human Genetics 2014, 23: 116-123. PMID: 24667780, PMCID: PMC4266733, DOI: 10.1038/ejhg.2014.47.Peer-Reviewed Original ResearchAllelesAmino Acid SequenceChromosomes, Human, Pair 22DNA Copy Number VariationsEnvironmentGene FrequencyGenetic Association StudiesGenetics, PopulationGenome-Wide Association StudyGenotypeHaplotypesHumansIntramolecular OxidoreductasesMacrophage Migration-Inhibitory FactorsModels, GeneticMolecular Sequence DataMultigene FamilyRisk FactorsSelection, GeneticSequence AlignmentSkin Pigmentation
2013
Functional variation of the transthyretin gene among human populations and its correlation with amyloidosis phenotypes
Polimanti R, Di Girolamo M, Manfellotto D, Fuciarelli M. Functional variation of the transthyretin gene among human populations and its correlation with amyloidosis phenotypes. Amyloid 2013, 20: 256-262. PMID: 24111657, DOI: 10.3109/13506129.2013.844689.Peer-Reviewed Original ResearchConceptsHuman populationTTR-related amyloidosisCis-regulatory variantsGenetic variantsNon-coding variantsGenomes Project databaseAdditional genetic variantsDisease-causing mutationsGene functionTranscription factorsKb regionCardiac developmentSilico analysisFunctional variationTTR geneRegulatory functionsGenotype-phenotype correlationGenesFunctional impactDisease phenotypeNon-African individualsSignificant diversityMutationsPhenotypeTransthyretin geneIntronic 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 ResearchPhenotype versus Genotype Methods for Copy Number Variant Analysis of Glutathione S‐Transferases M1
Piacentini S, Polimanti R, De Angelis F, Iorio A, Fuciarelli M. Phenotype versus Genotype Methods for Copy Number Variant Analysis of Glutathione S‐Transferases M1. Annals Of Human Genetics 2013, 77: 409-415. PMID: 23731058, DOI: 10.1111/ahg.12025.Peer-Reviewed Original ResearchConceptsCopy number variantsGlutathione S-transferaseAnalysis of CNVsHuman populationCopy number variant analysisNumber variant analysisProtein functionSingle nucleotide polymorphismsGenetic association studiesGSTM1 copy number variantAssociation studiesCNV frequencyGenotype methodMissense substitutionsNumber variantsPhenotype analysisGenesNucleotide polymorphismsS-transferaseMissense variantsGenetic associationVariant analysisPhenotypeGSTM1 geneFunctional effectsAntioxidant 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 metabolismGlutathione S-transferase polymorphisms, asthma susceptibility and confounding variables: a meta-analysis
Piacentini S, Polimanti R, Simonelli I, Donno S, Pasqualetti P, Manfellotto D, Fuciarelli M. Glutathione S-transferase polymorphisms, asthma susceptibility and confounding variables: a meta-analysis. Molecular Biology Reports 2013, 40: 3299-3313. PMID: 23307299, DOI: 10.1007/s11033-012-2405-2.Peer-Reviewed Original Research
2012
Genetic variability of glutathione S-transferase enzymes in human populations: Functional inter-ethnic differences in detoxification systems
Polimanti R, Carboni C, Baesso I, Piacentini S, Iorio A, De Stefano GF, Fuciarelli M. Genetic variability of glutathione S-transferase enzymes in human populations: Functional inter-ethnic differences in detoxification systems. Gene 2012, 512: 102-107. PMID: 23043933, DOI: 10.1016/j.gene.2012.09.113.Peer-Reviewed Original ResearchConceptsGenetic association studiesGenetic variabilityAssociation studiesHuman populationFunctional genetic differencesDetoxification genesGlutathione S-transferaseCellular detoxificationEnzymatic functionGlutathione S-transferase enzymesGST genesBiological processesGenetic differencesDetoxification systemGenesGST enzymesS-transferaseFunctional impactLoF variantsFunction variantsGSTEnzymeHapMap databaseGenetic polymorphismsKey role